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Biofiles
Pharmaceutical Drugs
and Drug Candidates
Antihypertensive Agents
Antilipemic Agents
Anticoagulants
Volume 7, Number 5
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Biofilescontents
Introduction 3
Antihypertensive Agents
5
Angiotensin-Converting
Enzyme (ACE) Inhibitors
5
Angiotensin II
Receptor Blockers (ARBs)
8
α1-Adrenoreceptor Blockers
11
β-Adrenergic Blockers
14
Calcium Channel Blockers (CCBs) 16
Highlights in this issue:
Scientists look to Sigma® Life Science
as a trusted source for small molecules
to use as research tools in their effort to
unravel the mystery of disease. In the
following pages, we will not only present
the approved therapeutics and drug
candidates to advance hypertension
research, but also some complementary
products such as antibodies, zinc finger nucleases, and more.
By providing you with best-in-class products across multiple stages of
your research, you can focus more on what matters most:
the new idea that will lead to the next breakthrough.
Upcoming issue:
The next issue of Biofiles will feature dietary
bioactives, specifically phytochemicals
and functional foods studied for their added
health and physiological benefits that
extend beyond normal nutritional value.
Their antioxidant, anti-proliferative and
anti-inflammatory activities contribute
to health maintenance and disease
prevention, making them optimal targets for pharmaceutical
alternatives and novel nutraceuticals.
Diuretics
19
Antilipemic Agents
21
3-Hydroxy-3-Methylglutaryl
Coenzyme A (HMG-CoA)
Reductase Inhibitors
21
Peroxisome Proliferator-Activated
Receptor (PPAR) Agonists
23
Acyl–Coenzyme A:Cholesterol
Acyltransferase (ACAT) Inhibitors
24
Anticoagulants25
Cover: Advances in pharmacology offer new
approved therapeutics and drug candidates
for the treatment of hypertension.
Technical content:
Sami Barghshoon
Product Manager – Bioactive Small Molecules
[email protected]
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3
Introduction
Sami Barghshoon
Product Manager – Bioactive Small Molecules
[email protected]
The development of effective medications
has led to progress in controlling both
blood pressure and cholesterol level.1-2
Antihypertensive and antilipemic agents
have vastly improved the treatments
available for hypertension and the quality
of life of individuals with this condition.
In 2011, there were 299 drug candidates
under development and 5,701 clinical trials
(Open Studies only) worldwide.3-4 From
this group, 27 drug candidates are under
evaluation for hypertension in 664 clinical
trials and 43 candidates in 103 clinical trials
for lipid disorders.
The majority of hypertension clinical trials
focus on combination therapies while lipid
disorders examine the combination of
lifestyle and medication intervention on
managing the disease.
Much of the groundwork for approved
therapeutics and drug candidates under
development came from extensive basic
research in hypertension.5 Researchers are
continually working to discover new ways to
approach the R&D process; researchers must
creatively tackle unforeseen challenges and
thoroughly collect data on all aspects of the
drug’s safety and efficacy.
Sigma® Life Science is currently collaborating
with Pfizer to provide you access to
several of their approved therapeutics and
drug candidates for your research efforts.
Our bioactive small molecules portfolio also
extends to include compounds from GSK,
Merck, AstraZeneca, and more.
We work closely with academic and
government institutions. Along with
your peers from the Broad Institute
and Northeastern University, we select
compounds to provide you with the
latest and most relevant research tools
for evaluating drug targets for the study
of hypertension.
By ensuring a comprehensive portfolio,
we make it easier for you to find the needed
approved therapeutics and drug candidates
for cardiovascular research. That means
your flashes of inspiration and persistent
dedication might lead to new treatments
for hypertension sooner than you expected.
This Biofiles issue concentrates on our
selection of approved therapeutics
and drug candidates for hypertension.
Our portfolio includes antihypertensive
agents such as:
•Angiotensin converting enzyme inhibitors
•Angiotensin receptor blockers
•β-adrenoreceptor blockers
•Calcium channel blockers
•Thiazide diuretics
We also explore antilipemic—HMG-CoA
reductase and ACAT inhibitors—and
anticoagulant agents. Complementary
products such as antibodies, peptides,
biomolecules (naturally-derived compounds),
and zinc finger nucleases are included.
4
And we don’t offer a “one size fits all.”
Sigma® Life Science offers a host of products
and services to support your research,
including our Library of Pharmacologically
Active Compounds LOPAC®, knockout
rat models from SAGE® laboratories,
and MISSION® ID Library for gene target
identification. We aim to provide elegant
solutions that are tailored to your specific
research needs.
Basic and clinical research continue to
make remarkable progress in understanding
cardiovascular biology. At the heart of this
progress is our commitment to provide you
with the best tools to do your best work in
advancing the promise of science.
References
1.Roger et al. 2011. Heart disease and stroke
statistics-2011 update: A report from the American
Heart Association. Circulation 123:e18-e209.
2. Arima, H. and Chalmers, J. 2011. PROGRESS: Prevention
of recurrent stroke. J Clin Hypertens 13:693-702.
3. PhRMA. 2011. Medicines in development for heart
disease and stroke. http://www.phrma.org/sites/default/
files/422/heart2011.pdf
4. NIH. 2011. Clinical Trials: Open studies in cardiovascular
disease. http://www.clinicaltrials.gov
5. PhRMA. 2011. Pharmaceutical industry profile.
http://www.phrma.org/sites/default/files/159/phrma_
profile_2011_final.pdf
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5
Antihypertensive Agents
Antihypertensive Agents
ACE Inhibitors
Agents that inhibit angiontensin-converting
enzymes (ACE) and angiotensin II formation
are essential to cardiovascular medicine.1
These inhibitors are used not only to treat
essential hypertension and complications
associated with it, but also to prevent
cardiovascular, cerebrovascular, and renal
complications.2,3
The first oral ACE inhibitor therapeutic was
developed in the 1970s,4 and was soon
followed by other ACE inhibitors with more
attractive pharmacodynamic effects.
Millions of people use ACE inhibitors on
a daily basis to manage hypertension.
In the U.S., roughly 163 million prescriptions
were filled in 2009, making this class of
therapeutics the country’s fourth most
widely prescribed medicine.5
The U.S. Food and Drug Administration
(FDA) has approved 10 ACE inhibitors for the
treatment of hypertension and there are 15
ACE inhibitors approved worldwide.
Sigma® Life Science offers you all 15 approved
ACE inhibitors at competitive prices. We strive
to provide you with the highest quality of
approved therapeutics available. Look no
further than Sigma® Life Science for precision
and control over your research experiments.
For more information and a complete list of
small molecules and related products, visit
sigma.com/therapeutics.
References
1.Gradman et al. 2010. American society of hypertension
writing group. Combination therapy in hypertension.
J Am Soc Hyperten 4:42–50.
2.Ferguson et al. 1977. A specific orally active inhibitor
of angiotensin-converting enzyme in man. Lancet
1:775–8.
3. Re, RN. 2001. The clinical implication of tissue renin
angiotensin systems. Curr Opin Cardiol 16:317–327.
4.Ondetti et al. 1977. Design of specific inhibitors of
angiotensin-converting enzyme: new class of orally
active antihypertensive agents. Science 196:441–4.
5. Consumer Reports. 2011. Using ACE Inhibitors
to treat high blood pressure and heart disease.
http://consumerreportshealth.org
ACE Inhibitors – Approved Therapeutics
Name
Structure
Captopril
OH
N
HS
O
CAS No.
Cat. No.
62571-86-2
C4042-5G
C4042-25G
116-38-1
E3256-250MG
E3256-1G
76095-16-4
E6888-250MG
E6888-1G
E6888-5G
84680-54-6
E9658-5MG
E9658-25MG
88889-14-9
F1308-5MG
F1308-25MG
O
CH3
Edrophonium chloride
H3C CH3
H3C
N
OH
Cl
Enalapril maleate salt
CO2CH2CH3
N
N
H
HO
OH
O
Enalaprilat dihydrate
COOH
O
O
O
OH
N
H
• 2H2O
CH3
O
O
N
OH
Fosinopril sodium
O
P
O
ONa
N
O
O
i-Pr O
O
CH3
6
ACE Inhibitors – Approved Therapeutics (continued)
Name
Structure
Imidapril hydrochloride
O
O
O
H
N
N
O CH3
N
CH3
HO
Itopride hydrochloride
O
122892-31-3
SML0033-10MG
SML0033-50MG
83915-83-7
L6292-100MG
L6292-250MG
82586-52-5
M0821-50MG
M0821-100MG
107133-36-8
P0094-50MG
P0094-250MG
101-26-8
P9797-1G
P9797-5G
82586-55-8
Q0632-250MG
Q0632-500MG
87333-19-5
R0404-100MG
R0404-250MG
87679-37-6
T4827-10MG
T4827-50MG
81938-43-4
Z1252-5MG
Z1252-25MG
CH3
• HCl
N
H
H3CO
CH3
N
CH3
O
Lisinopril
NH2
O
Cat. No.
SML0148-10MG
SML0148-50MG
• HCl
O
H3CO
CAS No.
89396-94-1
OH
N
N
H
O
Moexipril hydrochloride
OH
O
• 2H2O
O
H3CO
OH
O
(S)
N
H3CO
• HCl
(S)
H3C
H3C
O
NH
(S)
O
Perindopril erbumine
O
H
• H3C
OH
H
O
N
O
H
N
O
CH3
CH3
CH3
Pyridostigmine bromide
CH3
N
CH3
O
O
N
CH3
Quinapril hydrochloride
Br
O
• HCl
OH
N
H
N
O
H3C
Ramipril
O
O
C2H5OOC
H
CH3
HOOC
CH3
N
H
Trandolapril
CH3
NH2
CH3
H
N
O H
O
OH
H
O
N
O
H
N
O
Ph
CH3
Zofenopril calcium
Ph
S
O
N
O
CH3
O
S
Ca2+
O
CH3
2
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7
Angiontensin converting enzyme (ACE) inhibitors are not the only products available at Sigma® Life Science for this target class. You can
also find antibodies, biomolecules, peptides, and zinc finger nucleases. We offer you more resources so you can spend less time looking
for products and more time on your research.
Antibodies to ACE
Product Name
Host
Gene Symbol
Species Reactivity Application
Anti-ACE
rabbit
Clone No. Form
-
affinity isolated antibody
ACE, human
human
IHC (p)
PA
Prestige Antibody
✔
Cat. No.
HPA029298-100UL
Monoclonal Anti-ACE
mouse
6A4
purified immunoglobulin
ACE, human
human
ELISA (i)
WB
-
WH0001636M1-100UG
Monoclonal Anti-ACE
mouse
4B10
purified immunoglobulin
ACE, human
human
ELISA (c)
ELISA (i)
WB
-
SAB1403725-100UG
Biochemicals for ACE Research
Name
Structure
(Z)-Guggulsterone
CH3
H3C
H3C
H
H
CAS No.
Cat. No.
39025-23-5
G5168-5MG
G5168-25MG
102518-79-6
H5902-1MG
207671-44-1
Q1250-5G
Q1250-10G
Q1250-50G
94-07-5
S0752-5G
83-67-0
T4500-25G
T4500-100G
O
H
O
(−)-Huperzine A
H3C
NH2
H3C
H
HN
O
Quinine hemisulfate salt monohydrate
H2C
• H2SO4
N
HO
H3CO
• 2H2O
N
2
(±)-Synephrine
-
Theobromine
O
O
CH3
N
HN
N
N
CH3
Proteins and Peptides for ACE Research
Product Name
Gene Symbol
Purity
CAS No.
Cat. No.
Abz-LFK(Dnp)-OH trifluoroacetate salt
-
≥98%, HPLC
-
A5855-1MG
Angiotensin Converting Enzyme from rabbit lung
ACE
-
9015-82-1
A6778-.1UN
A6778-.25UN
A6778-1UN
A6778-2UN
A6778-5UN
Angiotensin Converting Enzyme Inhibitor
-
≥95%, TLC
35115-60-7
A0773-1MG
A0773-5MG
Angiotensin I human acetate salt hydrate
AGT
≥90%, HPLC
70937-97-2
A9650-1MG
A9650-5MG
A9650-10MG
A9650-50MG
Angiotensin II human
AGT
≥93%, HPLC
4474-91-3
A9525-1MG
A9525-5X1MG
A9525-5MG
A9525-10MG
A9525-50MG
8
Proteins and Peptides for ACE Research (continued)
Product Name
Gene Symbol
Purity
CAS No.
Cat. No.
N-[3-(2-Furyl)acryloyl]-Phe-Gly-Gly
ACE
ACE2
ACE3
-
64967-39-1
F7131-25MG
F7131-100MG
F7131-500MG
Hippuryl-His-Leu acetate salt
ACE
ACE2
ACE3
-
103404-54-2
H4884-25MG
H4884-100MG
H4884-500MG
H4884-1G
N-Hippuryl-His-Leu hydrate
ACE
ACE2
ACE3
≥98%, HPLC
207386-83-2
H1635-25MG
H1635-100MG
H1635-500MG
H1635-1G
Zinc Finger Nucleases for ACE Research
Name
Gene Symbol
Cat. No.
CompoZr® Knockout ZFN Kit
ACE
CKOZFN1813-1KT
CompoZr® Knockout ZFN Kit, ZFN plasmid only
Ace
CKOZFND26143-1KT
CompoZr® Knockout ZFN Kit, ZFN plasmid only
ACE
CKOZFND1813-1KT
ARBs
Hypertension can result from excessive
activity of the renin-angiotensin-aldosterone
system (RAAS) and this overactivity can
injure critical organs such as the heart and
blood vessels.1
In the 1990s, angiotensin II receptor blockers
(ARBs) became commercially available to
block the activity of RAAS.2
Unlike ACE inhibitors which prevent
angiotensin I conversion to II, ARBs bind to
the angiotensin II AT1 receptor, blocking the
cellular actions triggered by angiotension II.3
Over the past two decades, studies in the
laboratory and clinic have documented
that ARBs, either alone or in combination
with thiazide-type diuretics, reduce blood
pressure in animals and humans.4
The pharmacological differences among
ARBs are how they exert their effects. Some
ARBs compete with angiotensin II in a
concentration-dependent manner for AT1
receptor binding while others irreversibly
bind to the receptor.5
At Sigma® Life Science, you will find
six approved therapeutics in this target class.
We strive to provide you with a
comprehensive selection of approved
therapeutics so you don’t have to spend
a lot of time and effort to find them.
Visit sigma.com/therapeutics for a listing
of all approved drugs and drug candidates.
References
1. Savoia C, Schiffrin EL. 2007. Vascular inflammation in
hypertension and diabetes: molecular mechanisms and
therapeutic interventions. Clin Sci 112:375–384.
2. Ferrario, CM. 2006. Role of angiotensin II in cardiovascular disease therapeutic implications of more than a
century of research. J Renin Angiotensin Aldosterone Syst
7:3–14.
3. Oparil, S. 2000. Newly emerging pharmacologic
differences in angiotensin II receptor blockers. Am J
Hypertens 13:18S–24S.
4.Addison et al. 2011. Angiotensin receptor blockers:
Pharmacology, efficacy, and safety. J Clin Hypertens
13:677–86.
5. Munger, MA. 2011. Use of angiotensin receptor blockers in cardiovascular protection: current evidence and
future directions. Pharmacy & Therapeutics 36:22-40.
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ARBs - Approved Therapeutics
Name
Structure
Candesartan cilexetil
H3C
N
O
O
CH3
O
N N
N
N
H
O
N
O
Cat. No.
SML0245-10MG
SML0245-50MG
144143-96-4
E2535-10MG
E2535-50MG
138402-11-6
I2286-10MG
I2286-50MG
124750-99-8
61188-100MG
144701-48-4
T8949-10MG
T8949-50MG
137862-53-4
SML0142-10MG
SML0142-50MG
O
Eprosartan mesylate
N
H3C
CAS No.
145040-37-5
O
• H3C S OH
O
S
OH
N
O
OH
O
Irbesartan
N
O
CH3
N
N
N
NH
N
Losartan potassium
Cl
N
HO
CH3
N
N
KN N
Telmisartan
N
CH3
N
N
N
CH3
Valsartan
CH3
N
O
OH
HN N
N
N
O
O
H3C
N
H 3C
OH
CH3
In addition to angiotensin II receptor blockers (ARBs), Sigma® Life Science also offers antibodies, peptides, and zinc finger nucleases for this
target class. At sigma.com, you can search our collection and obtain more information about any of our products.
Antibodies to Angiotensin II Receptor Type 1 (AGTR1)
Product Name
Host
Form
Gene Symbol
Species Reactivity
Application
Anti-AGTR1
rabbit
affinity isolated antibody
AGTR1, human
human
IHC (p)
PA
Prestige Antibody
✔
HPA003596-100UL
Cat. No.
Anti-AGTR1
rabbit
affinity isolated antibody
AGTR1, human
human
mouse
rat
ELISA (i)
IHC
WB
-
SAB3500209-100UG
Anti-AGTR1
rabbit
affinity isolated antibody
AGTR1, human
bovine
canine
human, mouse, rat
pig
rabbit
WB
-
SAB2100073-50UG
Anti-AGTR1/AT1
goat
affinity isolated antibody
AGTR1, human
human
mouse
rat
ELISA (i)
WB
-
SAB2500038-100UG
9
10
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Alpha (α) Blockers
α1-Antagonists (α-blockers) selectively
block post-synaptic α1-adrenoreceptors and
prevent catecholamine-induced constriction
of arteries and venous vascular beds, thereby
lowering blood pressure.1
However, α-blockers administered over time
increase an individual's extracellular fluid and
plasma volumes.2 This expansion typically
manifests as weight gain and an attenuation
of blood pressure. Therefore, these
therapeutics are contraindicated in persons
with heart failure because of their ability to
expand extracellular and plasma volumes.3
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phentolamine and phenoxybenzamine,
as well as the quinazoline-selective
α1-adrenoreceptor blockers.
One therapeutic strategy to counter the
induced expansion is the administration
of α1-adrenoreceptor antagonists with
diuretics such as chlorthalidone or
hydrochlorothiazide.4 The diurectics
mitigate the expansion of the extracellular
and plasma volumes, providing significant
incremental reductions in blood pressure.
Diuretics available from Sigma® Life Science
are discussed in a subsequent section.
Visit sigma.com/therapeutics for a listing
of approved drugs and drug candidates.
References
1.Neaton et al. 1993. Treatment of mild hypertension
study. JAMA 270:713–24.
2.Wright et al. 2008. Clinical outcomes by race in hypertensive patients with and without metabolic syndrome.
Arch Intern Med 168:207–17.
3.David et al. 2008. Heart failure with preserved and
reduced left ventricular ejection fraction in antihypertensive and lipid-lowering treatment to prevent heart
attack trial. Circulation 118:225E–67E.
4.Barzillay et al. 2004. Cardiovascular outcomes using
doxazosin vs chlorthalidone for the treatment of
hypertension in older adults with and without glucose
disorders. J Clin Hypertens 6:116–25.
Sigma Life Science is your definitive
source for all approved α-blockers
that are available at competitive prices.
This includes the first generation of
nonselective α-receptor antagonists,
α-Blockers – Approved Therapeutics
Name
Structure
CAS No.
Cat. No.
Alfuzosin hydrochloride
NH2
81403-68-1
A0232-5MG
A0232-25MG
77883-43-3
D9815-50MG
D9815-250MG
-
F4303-5MG
F4303-25MG
-
N158-25MG
N158-100MG
63-92-3
B019-250MG
H3CO
• HCl
N
H3CO
N
Doxazosin mesylate
O
N
CH3
NH2
H3CO
N
H3CO
N
N
O
N
H
O
• H3C S OH
O
O
N
O
O
Fiduxosin hydrochloride
O
H
O
H
N
O
N
O
S
HN
N
• HCl
N
Naftopidil hydrochloride hydrate
OCH3
N
N
• HCl
• xH2O
O
OH
Phenoxybenzamine hydrochloride
CH3
O
N
Cl
• HCl
11
12
α-Blockers – Approved Therapeutics (continued)
Name
Structure
CAS No.
Cat. No.
CH3
73-05-2
P7547-100MG
P7547-500MG
19237-84-4
P7791-50MG
P7791-250MG
P7791-1G
63590-64-7
T4680-50MG
T4680-250MG
64887-14-5
U100-100MG
U100-500MG
Phentolamine hydrochloride
N
N
H
N
OH
HCl
Prazosin hydrochloride
NH2
H3CO
• HCl
N
H3CO
N
N
N
O
O
Terazosin hydrochloride
NH2
H3CO
N
H3CO
• HCl
N
N
N
O
O
Urapidil hydrochloride
N
CH3
N
O
N CH2CH2CH2 NH
OCH3
N
• HCl
O
CH3
α-Blocker Drug Candidates
Name
Structure
A-315456
N
CAS No.
Cat. No.
-
A6351-5MG
A6351-25MG
-
L3040-5MG
L3040-25MG
N
H
O
N S
H
O
L-765,314 hydrate
NH2
H3CO
H3CO
• xH2O
O
N
N
CH3
N
H
O
N
N
O
t-Bu
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13
Sigma® Life Science also offers antibodies, biomolecules, and zinc finger nucleases for the study of α1-adrenoreceptors. With more resources,
you can spend less time looking for products and more time on your research.
Visit sigma.com to search through our extensive product portfolio of antihypertensive agents.
Antibodies to α-Adrenergic Receptor Proteins (ADRA1A)
Species
Reactivity
Application
Prestige
Antibody
Product Name
Host
Clone No. Form
Gene Symbol
Anti-ADRA1A
rabbit
-
affinity isolated antibody
ADRA1A, human
human
mouse
rat
ELISA (i)
IF (i)
-
Cat. No.
SAB4500530-100UG
Anti-ADRA1A
rabbit
-
affinity isolated antibody
ADRA1A, human
human
IHC (p)
PA
✔
HPA029678-100UL
Monoclonal Anti-ADRA1A
mouse
4C7
purified immunoglobulin
ADRA1A, human
human
ELISA (i)
WB
-
WH0000148M1-100UG
Anti-ADRA1A, C-Terminal
rabbit
-
affinity isolated antibody
ADRA1A, human
human
ELISA (i)
WB
-
SAB4500529-100UG
Monoclonal Anti-ADRA1A,
(N-terminal)
mouse
5G8
purified immunoglobulin
ADRA1A, human
human
ELISA (i)
WB
-
SAB1403528-100UG
Anti-α1 Adrenergic Receptor
rabbit
-
affinity isolated antibody
Adra1d, mouse
ADRA1B, human
ADRA1D, human
Adra1d, rat
ADRA1A, human
human
mouse
rat
IF (i)
WB
-
A270-100UL
Anti-α1C Adrenergic Receptor
rabbit
-
affinity isolated antibody
ADRA1A, human
human
IHC (p)
-
A4604-50UL
Biochemicals for α1-Adrenoreceptor Research
Name
Benoxathian hydrochloride
Structure
S
H3CO
H
N
O
Cat. No.
B016-10MG
B016-25MG
770-05-8
O0250-1G
O0250-5G
O0250-10G
O
OCH3
• HCl
(±)-Octopamine hydrochloride
CAS No.
92642-97-2
NH2
HO
HCl
OH
Zinc Finger Nucleases for α1-Adrenoreceptor Research
Name
Gene Symbol
Cat. No.
CompoZr® Knockout ZFN Kit
ADRA1A
CKOZFN2898-1KT
CompoZr® Knockout ZFN Kit, ZFN plasmid only
Adra1a
CKOZFND26353-1KT
CompoZr® Knockout ZFN Kit, ZFN plasmid only
Adra1a
CKOZFND50299-1KT
CompoZr® Knockout ZFN Kit, ZFN plasmid only
ADRA1A
CKOZFND2898-1KT
14
Beta (β) Blockers
The first β-adrenergic blockers (β-blockers)
were identified as antihypertensive agents
in the early 1960s.1,2 The first approved
drug, propranolol, was used as an adjunct
therapy to phentolamine in the treatment
of pheochromocytoma.3,4
In the U.S. and Europe, β-blockers are
recommended as a first-line treatment for
hypertension. This recommendation is based
on reduced mortality and morbidity in
large clinical trials. Most of the benefit from
β-blockers stems from secondary vascular
protection in established disease instead of
primary prevention.5
There is no consensus regarding how
β-blockers lower blood pressure and it
is probable that several mechanisms are
at work. Mechanisms to account for the
antihypertensive actions of β-blockers
include reduction in peripheral vascular
resistance and inhibition of renin release.3
β-blockers are not uniform in their various
pharmacologic effects. Some of the
differences between β-blockers include
sympathomimetic and membrane-stabilizing
activities, β1 selectivity, α1-adrenergicblocking, solubility in tissue, routes of
systemic elimination, potencies, and duration
of action.6 This variation contrasts with other
classes of antihypertensive drugs and may
be important in the selection of a drug for
clinical or research use.
β-blockers are taken by tens of millions
of Americans everyday. In 2009, these
therapeutics were the fifth most widely
prescribed class of medicines in the United
States with 128 million prescriptions filled.7
To date, the Food and Drug Administration
(FDA) has approved 15 β-blockers for oral
use in patients with systemic hypertension.
Sigma® Life Science is your only source for all
15 approved β-blockers. You’re more likely to
find the β-blockers for your research needs at
Sigma Life Science than anywhere else.
For a complete listing of all approved
drugs and drug candidates, visit
sigma.com/therapeutics.
References
1. Prichard BNC.1964. Hypotensive action of pronethalol.
Br Med J 1:1227–8.
2. Prichard BNC, and Gillam PMS. 1964. Use of propranolol
(Inderal) in the treatment of hypertension. Br Med J
2:725–7.
3. Frishman WH. 2011. α- and β-adrenergic blocking
drugs. In: Frishman WH, Sica DA (eds.). Cardiovascular
Pharmacotherapeutics, 3rd ed. Minneapolis, MN:
Cardiotext Inc. Pg 57–86.
4. Frishman WH, Sica DA. 2008. β-Adrenergic blockers. In:
Izzo JL Jr, Sica D, Black HR (eds.). Hypertension Primer,
4th ed. The Essentials of High Blood Pressure. Philadelphia, PA: Wolters Kluwer Lippincott Williams & Wilkins
Pg 446–50.
5.Chobanian et al. 2003. The Seventh report of the joint
national committee on prevention, detection, evaluation and treatment of high blood pressure: the JNC-7
report. JAMA 289:2560–72.
6. Frishman WH. 2008. β-Adrenergic blockers: a 50-year
historical perspective. Am J Ther 15:565–76.
7. Consumer Reports. 2011. Using β-blockers to treat high
blood pressure and heart disease. http://consumerreportshealth.org
β-Blockers – Approved Therapeutics
Name
Structure
Acebutolol hydrochloride
OH
O
O
H3C
H
N
O
OH
O
H
N
Betaxolol hydrochloride
OH
H
N
O
CH3
N
H
63659-19-8
B5683-10MG
B5683-50MG
O
O
104344-23-2
B2185-10MG
B2185-50MG
CH3
CH3
O
72956-09-3
C3993-50MG
C3993-250MG
81161-17-3
E8031-10MG
E8031-50MG
CH3
CH3
• HCl
O
H3C
A7655-1G
A7655-5G
A7655-25G
CH3
CH3
H2N
Bisoprolol hemifumarate salt
29122-68-7
CH3
• HCl
Atenolol
O
Cat. No.
A3669-1G
CH3
CH3
N
H
CAS No.
34381-68-5
O
• ½ HO
OH
O
OH
Carvedilol
O
OH
N
H
O
H3CO
N
H
Esmolol hydrochloride
O
CH3
H3C
N
H
OCH3
O
OH
• HCl
Order sigma.com/order
Technical service sigma.com/techinfo
sigma.com/lifescience
β-Blockers – Approved Therapeutics (continued)
Name
Structure
Labetalol hydrochloride
OH
H
N
CAS No.
Cat. No.
32780-64-6
L1011-5G
L1011-10G
56392-17-7
M5391-1G
M5391-5G
M5391-10G
42200-33-9
N1892-1G
N1892-5G
152520-56-4
N1915-10MG
N1915-50MG
28163-36-2
32838-10MG
13523-86-9
P0778-250MG
P0778-1G
318-98-9
P0884-1G
P0884-5G
P0884-25G
P0884-100G
959-24-0
S0278-25MG
S0278-100MG
26921-17-5
T6394-100MG
T6394-250MG
T6394-1G
CH3
HO
• HCl
NH2
O
(±)-Metoprolol (+)-tartrate salt
OH
OH O
H
N
O
CH3 • ½ HO
CH3
H3CO
Nadolol
OH
O
OH
OH
OH
O
HO
Nebivolol hydrochloride
CH3
CH3
CH3
H
N
F
F
H
O
H
N
H
OH
• HCl
O
OH
Penbutolol hydrochloride
• HCl
OH
Pindolol
OH
O
t-Bu
N
H
O
H
N
CH3
CH3
N
H
(±)-Propranolol hydrochloride
CH3
O
N
H
OH
CH3
• HCl
(±)-Sotalol hydrochloride
OH
O
S
H3C
N
O H
Timolol maleate salt
CH3
OH
N
O
S
N
O
•
CH3
• HCl
O
N
H
N
H
N
CH3
CH3
CH3
O
HO
OH
H
H
15
16
In addition to β-blockers, Sigma® Life Science also offers antibodies that target the β-adrenergic receptors. Visit sigma.com to search our entire
portfolio and obtain more information about any of our products.
Antibodies to Adrenergic β-1-Receptor Proteins (ADRB1)
Product Name
Host
Form
Gene Symbol
Species Reactivity
Application
Anti-ADRB1
goat
affinity isolated antibody
ADRB1, human
canine
human
mouse
rat
ELISA (i)
WB
-
SAB2500034-100UG
Anti-ADRB1
rabbit
affinity isolated antibody
ADRB1, human
human
mouse
rat
ELISA (i)
WB
-
SAB4500573-100UG
Anti-ADRB1
rabbit
affinity isolated antibody
ADRB1, human
canine
human, mouse, rat
pig
WB
-
SAB2100064-50UG
CCBs
Calcium channel blockers (CCBs) inhibit the
movement of extracellular calcium across
the cell membrane through ion-specific
channels. Although several types of channels
exist, CCBs target the L-type channels in
humans. Inhibition of the inward calcium
flux causes smooth vascular muscle cell
relaxation, resulting in vasodilation and
lowering of blood pressure.1
There are two groups of approved
therapeutics that target L-type
calcium channels, dihydropyridine
and nondihydropyridine compounds.
The two types bind to different sites on
the channel.2 However, nondihydropyridine
calcium channel blockers differ from
the dihydropyridine subclass in that they
are more negatively chronotropic and
inotropic. This difference is important for
patients who also require β-blockers to
manage their hypertension.
One aspect of CCBs that differentiate them
from other antihypertensive agents is their
ability to reduce blood pressure across
all patient groups, regardless of sex, race/
ethnicity, age, and dietary sodium intake.3
Currently, there are eight dihydropyridine
and two nondihydropyridine approved
therapeutics. These therapeutics are for
individual use or in combination with other
antihypertensive drugs, including statins.3
In 2009, CCBs were the ninth most widely
prescribed class of medicines in the United
States with 92 million prescriptions. CCBs not
only help people manage their high blood
pressure, angina, and certain heart rhythm
abnormalities, they can also be used to treat
migraines, poor circulation to the hands and
feet, and certain psychiatric disorders.4
Sigma Life Science currently offers all the
dihydropyridine approved therapeutics
except for clevidipine, which is not
available for research purposes. The two
nondihydropyridine approved therapeutics,
diltiazem (Cat. No. D2521) and verapamil
(Cat. No. V4629), can also be obtained from
Sigma Life Science.
Prestige Antibody Cat. No.
There are other approved CCBs that are
useful tools in hypertension research.
These research therapeutics are listed
below and include the two drug candidates
azelnidipine (Cat. No. A7106) and cilnidipine
(Cat. No. C1493).
At Sigma, we strive to provide you with the
largest selection of approved therapeutics
available. You’re more likely to find the
CCBs for your research needs at
sigma.com/therapeutics than anywhere else.
References
1. Abernethy DR and Schwartz JB. 1999. Calcium-antagonist
drugs. N Engl J Med 341:1447-57.
2. Materson BJ. 1995. Calcium channel blockers: is it
time to split the lump? Am J Hypertens 8:325-9.
3.Elliott et al. 2011. Calcium channel blockers. J Clin
Hypertens 13:687-9.
4. Consumer Reports. 2011. Using calcium channel
blockers to treat high blood pressure and heart disease.
http://consumerreportshealth.org
Order sigma.com/order
Technical service sigma.com/techinfo
sigma.com/lifescience
CCBs – Approved Therapeutics
Name
Structure
Amlodipine besylate
CAS No.
Cat. No.
111470-99-6
A5605-10MG
A5605-50MG
33286-22-5
D2521-1G
D2521-5G
D2521-10G
141625-93-6
D9696-10MG
D9696-50MG
72509-76-3
F9677-5MG
F9677-25MG
3717-88-2
F8304-10MG
F8304-50MG
122647-32-9
I9910-10MG
I9910-50MG
75695-93-1
I6658-5MG
I6658-25MG
-
M5441-5MG
M5441-25MG
54527-84-3
N7510-1G
N7510-5G
N7510-10G
21829-25-4
N7634-1G
N7634-5G
N7634-10G
N7634-25G
Cl
O
O
H3CO
H3C
O
O
N
H
OCH3
H
S
H
N
N CH2CH2
CH3
NH2
• C6H5SO3H
(+)-cis-Diltiazem hydrochloride
CH3
CH3
O C CH3
O
O
HCl
Dronedarone hydrochloride
CH3
N
O
CH3
O
O
H
H3C S N
O
CH3
O
Felodipine
• HCl
Cl
Cl
O
O
H3C
O
O
N
H
H3C
Flavoxate hydrochloride
O
N
CH3
CH3
O
O
• HCl
CH3
O
Ibutilide hemifumarate salt
CH3(CH2)5CH2
O
H
N S CH3
O
N
• ½ HO
O
N
N
O
O
CH3
H3CO
O
H3C
Mibefradil dihydrochloride hydrate
CH3
CH3
N
H
O
H3CO
F
O
N
N
CH3 H C
3
N
H
Nicardipine hydrochloride
CH3
• xH2O
• 2HCl
NO2
O
O
H3CO
O
H3C
OH
O
OH
CH3
Isradipine
O
N
H
• HCl
CH3
N
CH3
Nifedipine
O
CH3O C
CH3
N
H
NO2
C OCH3
O
CH3
17
18
CCBs – Approved Therapeutics (continued)
Name
Structure
Nimodipine
NO2
CH3 O
H3C
O
V4629-1G
V4629-5G
V4629-10G
OCH3
H3C
CH3
N
H
CH3
CN
H3CO
152-11-4
NO2
O
O
(±)-Verapamil hydrochloride
N0165-10MG
N0165-50MG
CH3
N
H
Nisoldipine
CH3
63675-72-9
OCH3
O
H3C
H3C
Cat. No.
N149-100MG
N149-500MG
O
O
H3C
CAS No.
66085-59-4
CH3
N
OCH3
OCH3
• HCl
OCH3
CCB Drug Candidates
Name
Structure
Azelnidipine
CAS No.
Cat. No.
123524-52-7
A7106-10MG
A7106-50MG
132203-70-4
C1493-10MG
C1493-50MG
NO2
CH3 O
H3C
O
O
N
O
H3C
N
H
NH2
Cilnidipine
NO2
O
H3CO
O
O
H3C
H
O
N
H
CH3
H
Calcium channel blockers (CCBs) are not the only products available at Sigma® Life Science for this target class. We also provide antibodies,
biomolecules, and zinc finger nucleases to complement your research. More product information can be obtained for the products listed
and others at sigma.com.
Antibodies to Calcium Channel Proteins
Product Name
Host
Clone No. Form
Gene Symbol
Anti-CACNA1C
goat
-
affinity isolated
antibody
CACNA1C, human human
ELISA (i)
WB
-
SAB2500182-100UG
Anti-CACNA1C
rabbit
-
affinity isolated
antibody
CACNA1C, human human
IHC (p)
PA
✔
HPA039796-100UL
Monoclonal Anti-CACNA1C,
(C-terminal)
mouse
4D10
purified
CACNA1C, human human
immunoglobulin
ELISA (c)
ELISA (i)
WB
-
SAB1402709-100UG
Anti-Calcium Channel
(α1 Subunit), Pan
rabbit
-
affinity isolated
antibody
Cacna1c, rat
Cacna1c, mouse
mouse
rat
IHC
WB
-
C1103-.05ML
C1103-.2ML
Anti-Calcium Channel
(Cardiac α1C Subunit) (L-type of
Voltage-gated Ca2+ Channel)
rabbit
-
affinity isolated
antibody
Cacna1c, rat
rabbit
rat
IP
WB CL
-
C4980-.05ML
C4980-.2ML
Anti-Calcium Channel
rabbit
(α1C Subunit) (L-type of Voltagegated Ca2+ Channel)
-
affinity isolated
antibody
Cacna1c, mouse
human
mouse
rabbit
rat
IHC
WB
-
C1603-.2ML
Anti-Calcium Channel CaV1.2
(human)
-
affinity isolated
antibody
CACNA1C, human mouse
Cacna1c, rat
rat
Cacna1c, mouse
WB
-
C1241-200UL
rabbit
Species Reactivity
Application
Prestige Antibody Cat. No.
Order sigma.com/order
Technical service sigma.com/techinfo
sigma.com/lifescience
19
Biochemicals for Calcium Channel Research
Name
Structure
S-Petasin
O
O
S
OH
HO
HO
P7912-25MG
P7912-100MG
P7912-250MG
6164-47-2
P8489-5MG
OH
O
O
O
O
60-82-2
CH3
O
Protopine hydrochloride
Cat. No.
P4243-1MG
P4243-5MG
CH2
O
CH3
CH3 CH3
Phloretin
CAS No.
70238-51-6
O
N
CH3
• HCl
Zinc Finger Nucleases for Calcium Channel Research
Name
Gene Symbol
Cat. No.
CompoZr® Knockout ZFN Kit
CACNA1C
CKOZFN2581-1KT
CompoZr® Knockout ZFN Kit, ZFN plasmid only
Cacna1c
CKOZFND27870-1KT
CompoZr® Knockout ZFN Kit, ZFN plasmid only
CACNA1C
CKOZFND2581-1KT
Diuretics
First-line agents in the treatment of
hypertension are the thiazide-type diuretics.
These therapeutics are proven to reduce
cardiovascular mortality and morbidity.
This reduction occurs in both systolic and
diastolic forms of hypertension.1
Hydrochlorothiazide (HCTZ) is the thiazidetype diuretic used most often. Another
proven thiazide-type therapeutic is
chlorthalidone, which resembles HCTZ
structurally but differs in its pharmacology.2
These compounds are well tolerated
antihypertensive agents with respect to
symptomatic and adverse side effects.3
Loop diurectics such as fuorsemide,
bumetanide, and torsemide are less effective
than the thiazide-type drugs in reducing
blood pressure. However, loop diuretics
are important in hypertensive patients
with significant fluid overload or advanced
renal failure.4
Diuretics can be successfully combined with
β-blockers, ACE inhibitors, ARBs, and CCBs.
The combination of a diuretic with any one
of these antihypertensive agents provides
the best effect in lowering blood pressure
when compared to combinations without
a diuretic.5
You can obtain HCTZ and many of the
loop diurectics from Sigma® Life Science at
competitive prices. There are biomolecules
and peptides also available at Sigma.
We strive to provide you with the largest
selection of products so you can focus more
on your research.
You’re more likely to find the agents for your
research needs at Sigma Life Scienve than
anywhere else.
References
1.Ernst et al. 2010. Meta-analysis of dose-response
characteristics of hydrochlorothiazide and
chlorthalidone: effects on systolic blood pressure and
potassium. Am J Hypertens 23:440-6.
2.Carter et al. 2004. Hydrochlorothiazide versus
chlorthalidone: evidence supporting their
interchangeability. Hypertension 43:4-9.
3.Psaty et al. 1997. Health outcomes associated with
antihypertensive therapies used as first-line agents.
A systematic review and meta-analysis. JAMA 277:739-45.
4.Vargo et al. 1995. Bioavailability, pharmacokinetics, and
pharmacodynamics of torsemide and furosemide in
patients with congestive heart failure. Clin Pharmacol
Ther 57:601-9.
5.Materson et al. 1993. Single-drug therapy for
hypertension in men: A comparison of six antihypertensive agents with placebo. N Engl J Med 328:914-21.
20
Diuretics – Approved Therapeutics and Biochemicals
Name
Structure
Hydrochlorothiazide
H
N
Cl
O
H2N S
O
Bumetanide
CAS No.
Cat. No.
58-93-5
H4759-5G
H4759-25G
H4759-100G
28395-03-1
B3023-250MG
B3023-1G
107724-20-9
E6657-10MG
E6657-50MG
54-31-9
F4381-1G
F4381-5G
F4381-10G
F4381-25G
52-01-7
S3378-1G
S3378-5G
396-01-0
T4143-10G
T4143-25G
17560-51-9
M1195-5MG
M1195-25MG
487-36-5
SML0073-1MG
SML0073-5MG
NH
S
O O
NHCH2CH2CH2CH3
O
HO C
O
O S O
NH2
Eplerenone
O
H3C O
O
H3C
H
H
O
OCH3
O
Furosemide
O
OH
H
N
O
H2N S
O
O
Cl
Spironolactone
O
H3C
H3C
O
H
H
H
S
O
CH3
O
Triamterene
NH2
N
H2N
Metolazone
N
O
N
H
N
Cl
H2N
N
CH3
N
S
O
NH2
CH3
O
Pinoresinol
OCH3
OH
O
H
H
O
HO
OCH3
Atrial Natriuretic Peptides
Product Name
Gene Symbol
Purity
CAS No.
Cat. No.
Atrial Natriuretic Peptide fragment 4-24 frog
anf-A
≥97%, HPLC
118691-44-4
A0804-.1MG
A0804-.5MG
Atrial Natriuretic Peptide human
NPPA
≥97%, HPLC
91917-63-4
A1663-.1MG
A1663-.5MG
A1663-1MG
Order sigma.com/order
Technical service sigma.com/techinfo
sigma.com/lifescience
21
Antilipemic Agents
Antilipemic Agents
HMG-CoA Inhibitors
Randomized controlled clinical studies
have suggested 3-hydroxy-3-methylglutaryl
coenzyme A (HMG-CoA) reductase inhibitors
(statins) are effective in both primary and
secondary prevention of cardiovascular
disease (CVD) events.1 Primary prevention
refers to interventions that obviate the
first occurrence of a disease or condition,
secondary interventions deter reoccurrence.
The use of statins for primary intervention
is extensive for individuals with no previous
CVD but who have both elevated cholesterol
levels and high blood pressure, or individuals
who have coronary heart disease plus
multiple risk factors such as diabetes and
high blood pressure.2
While cholesterol has been singled out
as the primary factor in the development
of atherosclerosis, some research studies
References
suggest that C-reactive protein (CRP) may
also be a marker for the development and
progression of atherosclerosis.3-5 Elevated
basal levels of CRP can lead to inflammation
of arterial vessels, increasing the risk of
hypertension and cardiovascular disease.4
1.Pichandi et al. 2011. The role of statin drugs in combating cardiovascular diseases. Int J Cur Sci Res 1:47-56.
2. Goldenberg, N. and Glueck, C. 2009. Efficacy, effectiveness and real life goal attainment of statins in managing cardiovascular risk. Vasc Hlth & Risk Mgmt 5:369-76.
3. Kleemann, R. and Kooistra, T. 2005. HMG-CoA reductase
inhibitors: Effects on chronic subacute inflammation
and onset of atherosclerosis induced by dietary cholesterol. Cardiovasc & Haem Disorders 5:441-53.
4.Danesh et al. 2004. C-reactive P-protein and other
circulating markers of inflammation in the prediction of
coronary heart disease. N Engl J Med 350:1387-97.
5. Levinson, S. 2006. Inflammatory and long-term risk
markers. Clin Lab Med 26:553-70.
6. MacDonald, GP. 2010. Cost-effectiveness of rosuvastatin
for primary prevention of cardiovascular events according to Framingham risk score in patients with elevated
C-reactive protein. J Am Osteopath Assoc 110:427-36.
In 2010, rosuvastatin was approved in the
U.S. to prevent CVD in individuals over
50 with normal low density lipid (LDL)cholesterol levels and no history of heart
disease, but elevated CRP levels coupled
with one other risk factor such as high
blood pressure.6
You can obtain seven statins from
Sigma® Life Science, including the two drug
candidates, mevastatin (Cat. No. M2537) and
SR 12813 (Cat. No. S4194). We also offer
complementary products such as antibodies,
biomolecules, and zinc finger nucleases.
Visit sigma.com to discover all the products
relevant to your research.
HMG-CoA Inhibitors – Approved Therapeutics
Name
Structure
Atorvastatin calcium salt trihydrate
O
N
H
i-Pr
N
F
CAS No.
Cat. No.
134523-03-8
(anhydrous)
PZ0001-5MG
PZ0001-25MG
143201-11-0
(anhydrous)
SML0005-5MG
SML0005-25MG
-
SML0038-10MG
SML0038-50MG
Ca2+
OH O
HO
• 3H2O
O
2
Cerivastatin sodium salt hydrate
F
OH OH O
H3CO
H3C
ONa
CH3
N
CH3
Fluvastatin sodium hydrate
• xH2O
CH3
F
OH OH O
ONa
N
H3C
CH3
• xH2O
22
HMG-CoA Inhibitors – Approved Therapeutics (continued)
Name
Structure
Mevinolin from Aspergillus sp.
HO
O
CAS No.
Cat. No.
75330-75-5
M2147-25MG
-
P4498-25MG
79902-63-9
S6196-5MG
S6196-25MG
O
H
CH2
O
CH2
CH C O
H
H
CH3
CH3
CH3CH2
CH3
Pravastatin sodium salt hydrate
OH
NaO
O
HO
O
H
H3C
O
H3C
H
CH3
HO
Simvastatin
OH
H3C
H3C
O
O
H3C
O
H
O
CH3
H3C
HMG-CoA Inhibitor Drug Candidates
Name
Structure
Mevastatin
HO
O
CAS No.
Cat. No.
73573-88-3
M2537-5MG
126411-39-0
S4194-1MG
S4194-5MG
O
CH3CH2
SR 12813
HO
H3C
H3C
H3C
H CH2
O
CH2
CH C O
H
H
CH3
CH3
H3C CH3
CH3
P(O)(OC2H5)2
P(O)(OC2H5)2
Antibodies To HMG-CoA Enzymes
Product Name
Host
Form
Gene Symbol
Species Reactivity
Application Prestige Antibody Cat. No.
Anti-HMGCL
rabbit
affinity isolated antibody
HMGCL, human
human
IHC (p)
PA
WB
✔
HPA004727-100UL
Anti-HMGCR
rabbit
affinity isolated antibody
HMGCR, human
human
IHC (p)
PA
✔
HPA008338-100UL
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23
Biochemicals for HMG-CoA Research
Name
Structure
3-Hydroxy-3-methylglutaryl-CoA
reductase human
-
DL-3-Hydroxy-3-methylglutaryl
coenzyme A sodium salt hydrate
NH2
O H3C CH3
HN
O
OH
N
H
O
O
P O P O
OH OH
O
CAS No.
Cat. No.
-
H7039-250UG
-
H6132-5MG
H6132-10MG
H6132-25MG
580-72-3
40043-5MG-F
67604-48-2
N5893-1G
N5893-5G
N5893-25G
607-80-7
S9314-5MG
N
N
N
O
N
O
OH
NaO P O
ONa
OH
• xH2O
S
O HO CH3 O
Matairesinol
H3CO
HO
OH
O
O
(±)-Naringenin
OCH3
OH O
HO
O
OH
Sesamin
O
H
O
O
O
O
H
O
Zinc Finger Nucleases for HMG-CoA Research
Name
Gene Symbol
Cat. No.
CompoZr® Knockout ZFN Kit
HMGCR
CKOZFN10166-1KT
CompoZr® Knockout ZFN Kit, ZFN plasmid only
Hmgcr
CKOZFND33342-1KT
CompoZr® Knockout ZFN Kit, ZFN plasmid only
Hmgcr
CKOZFND55090-1KT
CompoZr® Knockout ZFN Kit, ZFN plasmid only
HMGCR
CKOZFND10166-1KT
PPAR Activators
Peroxisome proliferator-activated receptors
(PPAR) are nuclear receptors that function as
transcription factors on targeted genes when
heterodimerized with the retinoid
X receptor.1
PPAR-α is mainly involved in fatty acid
oxidation and is expressed in the liver,
kidney, and skeletal muscle, while PPAR-γ is
primarily involved in fat cell differentiation
and insulin sensitivity.2 Both are expressed
in smooth muscle cells and myocardium.
PPAR agonists have been shown to
reduce blood pressure in several models
of hypertension, correct endothelial
dysfunction, and exert anti-inflammatory
actions.3-5 Therefore, these therapeutic agents
are used to prevent vascular and cardiac
complications associated with hypertension.
References
1.Francis et al. 2003. PPAR agonists in the treatment of
atherosclerosis. Curr Opin Pharmacol 3:186-91.
2. Calkin, AC and Thomas, MC. 2007. PPAR agonists and
cardiovasuclar disease in diabetes. PPAR Research
2008:1-12.
3. Buchan, KW and Hassall, DG. 2000. PPAR agonists as
direct modulators of the vessel wall in cardiovascular
disease. Med Res Rev 20:350-66.
4.Inoue et al. 1998. Expression of peroxisome proliferatoractivated receptor α in primary cultures of human
vascular endothelial cells. Biochem Biophys Res Commun
246: 370-4.
5.Vu-Dac et al. 1998. The nuclear receptors peroxisome
proliferator-activated receptor α and Rev-erbα mediate
the species-specific regulation of apolipoprotein A-I
expression by fibrates. J Biol Chem 273:25713-20.
24
PPAR Activators – Approved Therapeutics
Name
Structure
Clofibrate
O
O
O
H3C CH3
Cl
Fenofibrate
O
Cl
CH3
H3C
ACAT Inhibitors
The enzyme acyl-coenzyme A:cholesterol
acyltransferase (ACAT) esterifies cholesterol
in a variety of tissues. In some animal models,
ACAT inhibitors act alone or in combination
with HMG-CoA inhibitors to exert their
antiatherosclerotic effects.1 This effect is
CH3
49562-28-9
F6020-5G
F6020-25G
F6020-100G
25812-30-0
G9518-5G
G9518-25G
CH3
CH3
CH3
O
Gemfibrozil
Cat. No.
C6643-250MG
C6643-1G
C6643-5G
C6643-10G
CH3
O
O
CAS No.
637-07-0
O
O
OH
H3C CH3
presumed to occur through the regulation
of cholesterol trafficking pathways in the liver
and vascular cells.2
Visit sigma.com/therapeutics for a listing
of the many approved therapeutics
and drug candidates available for your
cardiovascular research.
References
1.Nissen et al. 2006. Effect of ACAT inhibition on the
progression of coronary atherosclerosis. N Engl J Med
354:1253-63.
2.Bocan et al. 1998. HMG-CoA reductase and ACAT
inhibitors act synergistically to lower plasma cholesterol and limit atherosclerotic lesion development in
the cholesterol-fed rabbit. Atherosclerosis 139:21-30.
ACAT Inhibitor Drug Candidates
Name
Structure
Avasimibe
i-Pr
O
i-Pr
i-Pr
Sandoz 58-035
H
N
H3C
O
i-Pr
O
N S O
H
O
CAS No.
Cat. No.
166518-60-1
PZ0190-5MG
PZ0190-25MG
78934-83-5
S9318-5MG
S9318-25MG
i-Pr
CH3
Si CH2(CH2)8CH3
CH3
Order sigma.com/order
Technical service sigma.com/techinfo
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25
Anticoagulants
Anticoagulants
Pulmonary arterial hypertension (PAH) is
characterized as a progressive, incurable
disease and its treatment remains elusive.1
The mean survival rate is often less than
4 years and the median survival period is
2.8 years.2
In the 1980s, one treatment of PAH
focused on anticoagulant therapy. Fuster
et al. reported a statistically significant
improvement in the survival of patients
who had been treated with warfarin
compared to patients who had received no
anticoagulants.3 Rich et al. found the use of
anticoagulants may benefit patients with
PAH who do not respond to therapy with
calcium-channel blockers.4
Novel approaches to treat PAH include
Rho-kinase inhibitors and soluble guanylate
cyclase stimulators.5 Animal models have
shown these new classes of agents mitigate
the abnormal pulmonary vasoconstriction
associated with the disease.
Sigma® Life Science is the source for all
five approved anticoagulants listed below.
Sigma Life Science also offers the drug
candidate GSK-429286 (Cat. No. SML0231),
a ROCK1 inhibitor from GSK, the approved
drug Sildenafil (Cat. No. PZ0003),
a guanylate cyclase activator from Pfizer,
and the powerful anticoagulant heparin
(Cat. No. H3393).
Basic scientific research plays an important
role in finding new discoveries to improve
the quality of life for individuals affected with
this disease. We are working diligently to
provide you with the needed tools for your
research endeavors.
Visit sigma.com/therapeutics for a listing of
approved compounds and drug candidates
available for your cardiovascular research.
References
1.Johnson et al. 2006. Thrombotic arteriopathy and
anticoagulation in pulmonary hypertension. Chest
130:545-52.
2.Roger et al. 2011. Heart disease and stroke statistics–2011 update : A report from the American Heart
Association. Circulation 123:e18-e209.
3.Fuster et al. 1984. Primary pulmonary hypertension:
Natural history and the importance of thrombosis.
Circulation 70:580-7.
4.Rich et al. 1992. The effect of high doses of calciumchannel blockers on survival in primary pulmonary
hypertension. N Engl J Med 327:76- 81.
5.Murthy et al. 2010. New approaches to the treatment
of pulmonary hypertension: from bench to bedside.
Cardiol Rev. 8: 76-84.
Anticoagulants – Approved Therapeutics and Drug Candidates
Name
Structure
Acenocoumarol
O
OH
O
Argatroban monohydrate
Cl
O
Cat. No.
SML0074-10MG
SML0074-50MG
141396-28-3
A0487-5MG
A0487-25MG
120202-66-6
SML0004-10MG
SML0004-50MG
864082-47-3
SML0231-5MG
SML0231-25MG
61849-14-7
P6188-1MG
P6188-5MG
P6188-10MG
322-79-2
T6580-5MG
T6580-25MG
CH3
O
NO2
-
(S)-(+)-Clopidogrel hydrogensulfate
CAS No.
152-72-7
OCH3
• H2SO2
N
S
GSK-429286
-
Prostaglandin I2 sodium salt
O
O-
H
H
OH
Na+
O
OH
(CH2)4CH3
Triflusal
-
26
Other products that complement our approved anticoagulants include antibodies, biomolecules, and peptides. Visit sigma.com to search
our entire catalog and obtain more information for any of our products.
Antibody to Prothrombin IIA
Product Name
Host
Form
Gene Symbol
Species Reactivity
Application
Monoclonal Anti-PROC
mouse
purified immunoglobulin
PROC, human
human
ELISA (i)
WB
Prestige Antibody Cat. No.
-
WH0005624M1-50UG
Anti-PROC
rabbit
IgG fraction of antiserum
PROC, human
bovine
human
WB
-
AV41701-100UG
Anti-PROC
rabbit
affinity isolated antibody
PROC, human
human
IHC (p)
PA
✔
HPA005550-100UL
Biochemicals for Coagulation Research
Name
Structure
CAS No.
Cat. No.
-
9041-08-1
H3393-10KU
H3393-25KU
H3393-50KU
H3393-100KU
H3393-250KU
H3393-500KU
H3393-1MU
1949-20-8
O2256-25G
23180-57-6
P0038-25MG
171599-83-0
PZ0003-5MG
PZ0003-25MG
Heparin sodium salt from porcine
intestinal mucosa
Oxolamine citrate salt
O
N
N
O
OH O
HO
N
OH
O
Paeoniflorin
OH
OH
O
HO
O
Sildenafil citrate salt
O
H3C
N
HN
O
S
N
O
HO
O
H
O
O
H
OH
O
CH3
CH3
N
N
N
O
OH
CH3
CH3
HO
O
•
HO
O
O
OH
OH
Proteins and Peptides for Coagulation Research
Product Name
Gene Symbol
Purity
CAS No.
Cat. No.
[Tyr(SO3H)63]-Hirudin Fragment 54-65
-
≥95%, HPLC
109528-49-6
H6894-.1MG
H6894-1MG
Protein C, Activated, Fragment 390-404 human
PROC
~90%, HPLC
-
P5818-.5MG
Protein C from human plasma
PROC
≥90%, SDS-PAGE
42617-41-4
P2200-.1MG
Application Abbreviation Table
Application
Agglutination assay
ANA-indirect immunofluorescence
Array (antibody microarray)
Capture ELISA
Direct ELISA
Direct immunofluorescence
Dot blot
Dot immunobinding
Electron microscopy
Enzyme immunoassay
Flow cytometry
Immunoblotting
Immunoblotting (chemiluminescent)
Immunocytochemistry
Abbreviation
Agglut.
IF (ANA)
ARR
ELISA (c)
ELISA (d)
IF (d)
DB
DIBA
EM
EIA
FACS
WB
WB CL
ICC
Application
Immunoelectrophoresis
Immunohistochemistry
Immunohistochemistry (formalin-fixed, paraffinembedded sections)
Immunohistochemistry (frozen sections)
Immunoprecipitation
Indirect ELISA
Indirect immunofluorescence
Neutralization
Ouchterlony double diffusion
Particle immunofluorescence
Protein Array
Quantitative precipitin assay
Radioimmunoassay
Abbreviation
IEP
IHC
IHC (p)
IHC (f )
IP
ELISA (i)
IF (i)
Neutral
ODD
PIFA
PA
QPA
RIA
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More predictive and physiologically
relevant research models.
Advance your cardio research with
knockout rat models from SAGE® Labs.
Biovital.
Featuring the ApoE, Leptin, and Ldlr
knockout rat models, the Cardio Suite from
SAGE Labs is designed to support the study
of cardiovascular disease, obesity, diabetes,
atherosclerosis, and more.
Explore our collection
of knockout rat models
sageresearchmodels.com
27
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