Introduction to Fragment-Based Drug Discovery
... will be lost due to strain in the linker [10, 11]. Therefore, a frequent alternative to fragment linking is fragment growing, as shown in the bottom panel of Fig. 1. In this approach, a single fragment is progressively grown to make further interactions with the protein. It can be useful pedagogical ...
... will be lost due to strain in the linker [10, 11]. Therefore, a frequent alternative to fragment linking is fragment growing, as shown in the bottom panel of Fig. 1. In this approach, a single fragment is progressively grown to make further interactions with the protein. It can be useful pedagogical ...
Selective Inhibitors of Picornavirus Replication
... an important member of the cardioviruses. EMCV was isolated from several animals, as well as humans, and was shown to cause lesions in multiple organs, including heart, pancreas and CNS.6,7 The prototype of the enterovirus genus or of the picornavirus family in general, is poliovirus. This virus, ca ...
... an important member of the cardioviruses. EMCV was isolated from several animals, as well as humans, and was shown to cause lesions in multiple organs, including heart, pancreas and CNS.6,7 The prototype of the enterovirus genus or of the picornavirus family in general, is poliovirus. This virus, ca ...
A guide to drug discovery — opinion: Finding the sweet spot: the
... Box 1 | The drug discovery ‘sweet spot’ defined in the molecular mass–logP space A key challenge in medicinal chemistry can be illustrated by highlighting the ‘sweet spot’ in the chemical space defined by the two key (although not fully independent) physicochemical properties: molecular mass and cLo ...
... Box 1 | The drug discovery ‘sweet spot’ defined in the molecular mass–logP space A key challenge in medicinal chemistry can be illustrated by highlighting the ‘sweet spot’ in the chemical space defined by the two key (although not fully independent) physicochemical properties: molecular mass and cLo ...
Diuretics
... The reabsorption of electrolytes and water also occurs isosmotically in the proximal straight tubule or pars recta (S3 segment, Fig. 27.1) . By the end of the straight segment, between 65 and 70% of water and sodium, chloride, and calcium ions; 80 to 90% of bicarbonate and phosphate; and essentiall ...
... The reabsorption of electrolytes and water also occurs isosmotically in the proximal straight tubule or pars recta (S3 segment, Fig. 27.1) . By the end of the straight segment, between 65 and 70% of water and sodium, chloride, and calcium ions; 80 to 90% of bicarbonate and phosphate; and essentiall ...
screening in B-cell malignancies multitarget mechanism discovered
... combination activities used are from the matrix shown in panel A and are highlighted by white boxes. Comparison of panels A and B demonstrate how the dose-matrix format captures the breadth of combination activities at multiple ratios over a wide concentration range. (C) To assess synergy, each obse ...
... combination activities used are from the matrix shown in panel A and are highlighted by white boxes. Comparison of panels A and B demonstrate how the dose-matrix format captures the breadth of combination activities at multiple ratios over a wide concentration range. (C) To assess synergy, each obse ...
From fragment to clinical candidate—a historical perspective
... common in featureless and solvent exposed pockets (e.g. proteases or protein–protein interactions), which are less druggable. A number of alternative definitions of LE have been proposed [57–59] and there is also an increased interest on normalising potency by lipophilicity ...
... common in featureless and solvent exposed pockets (e.g. proteases or protein–protein interactions), which are less druggable. A number of alternative definitions of LE have been proposed [57–59] and there is also an increased interest on normalising potency by lipophilicity ...
The mechanism of action of aspirin
... glandin (PGs) researchers. Piper and Vane [7] used isolated lungs perfused with Krebs’ solution from sensitised guinea pigs. The purpose was to detect substances released during the anaphylactic reaction, including histamine and SRS-A, both of which had been known for many years as possible mediator ...
... glandin (PGs) researchers. Piper and Vane [7] used isolated lungs perfused with Krebs’ solution from sensitised guinea pigs. The purpose was to detect substances released during the anaphylactic reaction, including histamine and SRS-A, both of which had been known for many years as possible mediator ...
Discovery and development of ACE inhibitors
The discovery of an orally inactive peptide from snake venom established the important role of angiotensin converting enzyme (ACE) inhibitors in regulating blood pressure. This led to the development of Captopril, the first ACE inhibitor. When the adverse effects of Captopril became apparent new derivates were designed. Then after the discovery of two active sites of ACE: N-domain and C-domain, the development of domain-specific ACE inhibitors began.