Oncogenic regulation of tumor metabolic reprogramming
... a selective advantage to cancer cells. Therefore, metabolic properties of tumor cells are significantly different from those of non-transformed cells. In addition, tumor metabolic reprogramming is linked to drug resistance in cancer treatment. Accordingly, metabolic adaptations are specific vulnerab ...
... a selective advantage to cancer cells. Therefore, metabolic properties of tumor cells are significantly different from those of non-transformed cells. In addition, tumor metabolic reprogramming is linked to drug resistance in cancer treatment. Accordingly, metabolic adaptations are specific vulnerab ...
Dual Fatty Acid Synthase and HER2 Signaling
... binding or receptor overexpression in the case of HER2, leads to the recruitment of several adaptor proteins that mediate the activation of downstream signaling pathways [2, 3]. Among them, the phosphoinositide 3-kinase (PI3K)/protein kinase B (PKB/AKT)/mammalian target of rapamycin (mTOR) protein a ...
... binding or receptor overexpression in the case of HER2, leads to the recruitment of several adaptor proteins that mediate the activation of downstream signaling pathways [2, 3]. Among them, the phosphoinositide 3-kinase (PI3K)/protein kinase B (PKB/AKT)/mammalian target of rapamycin (mTOR) protein a ...
Sodium-Glucose Co-transporter 2 Inhibitor: A Perspective on
... inhibitors include BP, weight, visceral adiposity, hyperinsulinemia arterial stiffness, albuminuria, uric acid levels, and oxidative stress.4 These clinical findings suggest that it is now time to recognize that SGLT2 inhibitors may well be more than just another class of drugs to decrease blood glu ...
... inhibitors include BP, weight, visceral adiposity, hyperinsulinemia arterial stiffness, albuminuria, uric acid levels, and oxidative stress.4 These clinical findings suggest that it is now time to recognize that SGLT2 inhibitors may well be more than just another class of drugs to decrease blood glu ...
iPPI small molecule inhibitor of Protein
... orally available are known at this time) or can be allosteric inhibitors, thereby binding at, near or far away from the interface in cavities with recognition characteristics that could be highly similar to enzyme active sites. It would seem logical to explore and attempt to rationalize the propert ...
... orally available are known at this time) or can be allosteric inhibitors, thereby binding at, near or far away from the interface in cavities with recognition characteristics that could be highly similar to enzyme active sites. It would seem logical to explore and attempt to rationalize the propert ...
Protein Kinases - School of Medicine
... • This malignancy is unusual because it results from a single genetic alteration; most cancers result from multiple somatic genetic alterations ...
... • This malignancy is unusual because it results from a single genetic alteration; most cancers result from multiple somatic genetic alterations ...
Binding Studies of Type I, II, and III Kinase Inhibitors against Bcr
... and their associated signaling pathways are principally responsible for the regulation of intracellular processes. When abnormally expressed or controlled, kinase activity can cause cellular dysregulation and contribute to the onset of several diseases, including cancer. Based on the fundamental und ...
... and their associated signaling pathways are principally responsible for the regulation of intracellular processes. When abnormally expressed or controlled, kinase activity can cause cellular dysregulation and contribute to the onset of several diseases, including cancer. Based on the fundamental und ...
Fibroblast Growth Factor Receptor Inhibitors
... regulator of the Warburg effect and plays a key role in tumor cells. It also determines the glucose conversion rate and arranges the active tetrameric form during this process. It forms an inactive dimeric shape while developing new building blocks. Pyruvate kinase type M2 works as a switch between ...
... regulator of the Warburg effect and plays a key role in tumor cells. It also determines the glucose conversion rate and arranges the active tetrameric form during this process. It forms an inactive dimeric shape while developing new building blocks. Pyruvate kinase type M2 works as a switch between ...
FRAGMENT-BASED DRUG DESIGN: WHY IT'S SO IMPORTANT
... A series of therapeutically effective multi-kinase inhibitors have emerged over the last 5 years. The first of these was the Novartis Abl tyrosine kinase inhibitor Gleevec. Gleevec (imatinib) specifically and potently inhibits a narrow spectrum of tyrosine kinases including c-Fms, c-Kit, and PDGFRα ...
... A series of therapeutically effective multi-kinase inhibitors have emerged over the last 5 years. The first of these was the Novartis Abl tyrosine kinase inhibitor Gleevec. Gleevec (imatinib) specifically and potently inhibits a narrow spectrum of tyrosine kinases including c-Fms, c-Kit, and PDGFRα ...
Antiprotozoal drugs
... – especially in individuals lacking glucose-6phosphate dehydrogenase activity – enzyme activity has to be checked every time before initiation of therapy – might lead to life-threatening hemolysis of the fetus in pregnancy ...
... – especially in individuals lacking glucose-6phosphate dehydrogenase activity – enzyme activity has to be checked every time before initiation of therapy – might lead to life-threatening hemolysis of the fetus in pregnancy ...
The Emerging Role of Branched-Chain Amino Acids in Insulin
... synthesis and adsorption of fatty acids in a human intestinal cell line (NCI-H716), suggesting an intestinal mechanism for the beneficial effect of BCAAs [8]. In addition, the elevated BCAA levels induced insulinemic responses and insulintropic effects in mice [9,10]. Together with insulin, BCAAs al ...
... synthesis and adsorption of fatty acids in a human intestinal cell line (NCI-H716), suggesting an intestinal mechanism for the beneficial effect of BCAAs [8]. In addition, the elevated BCAA levels induced insulinemic responses and insulintropic effects in mice [9,10]. Together with insulin, BCAAs al ...
Lecture 22-Lutz
... • late 1990’s - inhibitors designed that preferentially bind COX-2, are equally effective as NSAIDs, but are reported to cause less GI damage. • 1998/1999 - Celebrex and Vioxx approved by FDA for osteoarthritis and rheumatoid arthritis. ...
... • late 1990’s - inhibitors designed that preferentially bind COX-2, are equally effective as NSAIDs, but are reported to cause less GI damage. • 1998/1999 - Celebrex and Vioxx approved by FDA for osteoarthritis and rheumatoid arthritis. ...
Inhibitors of Factor VIIa/Tissue Factor
... Arterioscler Thromb Vasc Biol. is available at http://atvb.ahajournals.org ...
... Arterioscler Thromb Vasc Biol. is available at http://atvb.ahajournals.org ...
BOSENTAN and POSSIBLE DRUG INTERACTIONS (No 1
... Background Sitaxentan is metabolised in the liver by Cytochrome P450 (CYP) isoenzymes CYP2C9 (major pathway) and CYP3A4 (minor pathway). Approximately half of an oral dose is excreted in the urine with the remainder eliminated in the faeces. Although there is potential for interaction with CYP2C9 an ...
... Background Sitaxentan is metabolised in the liver by Cytochrome P450 (CYP) isoenzymes CYP2C9 (major pathway) and CYP3A4 (minor pathway). Approximately half of an oral dose is excreted in the urine with the remainder eliminated in the faeces. Although there is potential for interaction with CYP2C9 an ...
Phospholipid signaling
... DGK to PA. Activation of PLD generates PA directly by hydrolysing structural phospholipids such as PC. PA can activate MAPK, CDPK, ion channels, and NADPH oxidase, all of which are involved in typical defencerelated responses. PA signalling is attenuated by its conversion to DGPP by PA kinase. All l ...
... DGK to PA. Activation of PLD generates PA directly by hydrolysing structural phospholipids such as PC. PA can activate MAPK, CDPK, ion channels, and NADPH oxidase, all of which are involved in typical defencerelated responses. PA signalling is attenuated by its conversion to DGPP by PA kinase. All l ...
FinMedChem2011
... O‐01 Gustav Boije af Gennäs. Design, synthesis and biological activity of urea derivatives as anaplastic lymphoma kinase inhibitors. O‐02 Adyary Fallarero. Targeting butyrylcholinesterase as a therapeutic strategy against Alzheimer’s disease. O‐03 Maija Lahtela‐Kakkonen. Structure‐based design of ...
... O‐01 Gustav Boije af Gennäs. Design, synthesis and biological activity of urea derivatives as anaplastic lymphoma kinase inhibitors. O‐02 Adyary Fallarero. Targeting butyrylcholinesterase as a therapeutic strategy against Alzheimer’s disease. O‐03 Maija Lahtela‐Kakkonen. Structure‐based design of ...
mTOR complex 2 (mTORC2) controls hydrophobic motif
... the T-loop Thr308 residue [12–15]. PDK1 also contains a PH domain that binds with high affinity to PtdIns(3,4,5)P3 and other phosphoinositides which co-localizes PDK1 and Akt at the plasma membrane [15,16]. Binding of PDK1 to PtdIns(3,4,5)P3 is important for the activation of Akt, but not SGK1, as a ...
... the T-loop Thr308 residue [12–15]. PDK1 also contains a PH domain that binds with high affinity to PtdIns(3,4,5)P3 and other phosphoinositides which co-localizes PDK1 and Akt at the plasma membrane [15,16]. Binding of PDK1 to PtdIns(3,4,5)P3 is important for the activation of Akt, but not SGK1, as a ...
The Role of Intracellular Signaling Pathways in the Pathogenesis of
... PI3K-mediated signals are complex signal transduction systems that are activated by various cytokines. However, stimulation of myeloma cell proliferation can be cytokine dependent or cytokine independent, and this activity correlates with disease activity. PI3KCA gene mutations are frequently seen i ...
... PI3K-mediated signals are complex signal transduction systems that are activated by various cytokines. However, stimulation of myeloma cell proliferation can be cytokine dependent or cytokine independent, and this activity correlates with disease activity. PI3KCA gene mutations are frequently seen i ...
Antidepressant Agents
... • 1- Antimuscarinic effects. Occur both centrally and peripherally. Patients with prostatic hypertrophy and glaucoma are cautioned. Tolerance develop to this effect. • 2- Postural hypotension and cardiac arrhythmias • 3- Manic excitement and delirium occur in patients with bipolar depression. • 4- T ...
... • 1- Antimuscarinic effects. Occur both centrally and peripherally. Patients with prostatic hypertrophy and glaucoma are cautioned. Tolerance develop to this effect. • 2- Postural hypotension and cardiac arrhythmias • 3- Manic excitement and delirium occur in patients with bipolar depression. • 4- T ...
Histone Deacetylase Inhibitors: Updated Studies in Various
... AR-42 8 has been shown to down regulate CD44, a glycoprotein likely to be associated with the lenalidomide / dexamethason treatment resistance in myeloma both in vitro (myeloma cells from patients) and in vivo (primary myeloma mouse model) [45]. Multiple myeloma cells are producing a large number of ...
... AR-42 8 has been shown to down regulate CD44, a glycoprotein likely to be associated with the lenalidomide / dexamethason treatment resistance in myeloma both in vitro (myeloma cells from patients) and in vivo (primary myeloma mouse model) [45]. Multiple myeloma cells are producing a large number of ...
... example, in treating patients with severe renal failure the clinician can thus choose between using a drug not eliminated by the kidney, where dose adjustment may not be necessary, or a drug which depends on renal excretion, where the dose may need to be reduced depending on the degree of renal fail ...
What is Xtend
... phosphatodyl-inositol-3-kinase pathway (PI3K). PI3K regulates glucose uptake through GLUT4 translocation and also increases amino acid uptake. Insulin, the body's "storage" hormone, works by activating the PI3K pathway. Interestingly, leucine ingestion causes insulin secretion, but leucine can also ...
... phosphatodyl-inositol-3-kinase pathway (PI3K). PI3K regulates glucose uptake through GLUT4 translocation and also increases amino acid uptake. Insulin, the body's "storage" hormone, works by activating the PI3K pathway. Interestingly, leucine ingestion causes insulin secretion, but leucine can also ...
Hutchison MediPharma R&D briefing Friday, 17 October 2014 9:30am to 1pm
... • Inadequate inhibition of primary target typically limits efficacy (e.g. Crizotinib) • Lack of potency means many compounds have high dose and poor PK (e.g. Lapatanib) • Precise mechanism of action still unclear in some patients (e.g. Sorafenib) ...
... • Inadequate inhibition of primary target typically limits efficacy (e.g. Crizotinib) • Lack of potency means many compounds have high dose and poor PK (e.g. Lapatanib) • Precise mechanism of action still unclear in some patients (e.g. Sorafenib) ...