Ivacaftor is a drug used in the treatment of cystic fibrosis (CF), a genetic disorder that affects the respiratory, digestive, and reproductive systems. It was approved by the US Food and Drug Administration (FDA) in 2012 and has since been used to treat patients with CF who have specific mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Ivacaftor is a small molecule that acts as a potentiator of CFTR, increasing its activity and improving the function of affected organs.
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Ivacaftor hydrate (VX-770) is a potentiator of CFTR targeting G551D-CFTR and F508del-CFTR with EC50 of 100 nM and 25 nM, respectively.IC50 Value: 25 nM (F508del-CFTR);100 nM (G551D-CFTR) [1]Target: F508del-CFTR/G551D-CFTRin vitro: In recombinant cells VX-770 increased CFTR channel open probability (P(o)) in both the F508del processing mutation and the G551D gating mutation. VX-770 also increased Cl(-) secretion in cultured human CF bronchial epithelia (HBE) carrying the G551D gating mutation on one allele and the F508del processing mutation on the other allele by approximately 10-fold, to approximately 50% of that observed in HBE isolated from individuals without CF [1].in vivo: At day 28, in the group of subjects who received 150 mg of VX-770, the median change in the nasal potential difference (in response to the administration of a chloride-free isoproterenol solution) from baseline was -3.5 mV (range, -8.3 to 0.5; P=0.02 for the within-subject comparison, P=0.13 vs. placebo), and the median change in the level of sweat chloride was -59.5 mmol per liter (range, -66.0 to -19.0; P=0.008 within-subject, P=0.02 vs. placebo) [2].Toxicity: Six severe adverse events occurred in two subjects (diffuse macular rash in one subject and five incidents of elevated blood and urine glucose levels in one subject with diabetes). All severe adverse events resolved without the discontinuation of VX-770 [2].Clinical trial: Roll-Over Study of Ivacaftor in Cystic Fibrosis Pediatric Subjects With a CFTR Gating Mutation. Phase 3
Prinaberel, also known as bexarotene, is a synthetic retinoid that has been used in medical, environmental, and industrial research. It was first approved by the US Food and Drug Administration (FDA) in 1999 for the treatment of cutaneous T-cell lymphoma. Since then, it has been studied for its potential therapeutic and environmental applications.
GSK1070916 is a potent and ATP-competitive inhibitor of Aurora kinases B and C (Kis = 0.38 and 1.5 nM, respectively). It is >250-fold selective for Aurora B and C over Aurora A. GSK1070916 inhibits proliferation of A549 lung cancer cells in vitro (EC50 = 7 nM). It also inhibits proliferation in a panel of 100 tumor cell lines (EC50s = <10 nM) via induction of polyploidy and apoptosis. In vivo, GSK1070916 inhibits histone H3 phosphorylation in a COLO 205 mouse xenograft model and induces tumor regression in an HL-60 mouse xenograft model. It also reduces tumor growth in 10 mouse xenograft models, including models of breast, colon, and lung carcinomas as well as leukemias. GSK1070916, also known as NMI-900 or GSK-1070916A, is an ATP-competitive inhibitor of the serine/threonine kinases Aurora B and C with potential antineoplastic activity. Aurora B/C kinase inhibitor GSK1070916A binds to and inhibits the activity of Aurora kinases B and C, which may result in inhibition of cellular division and a decrease in the proliferation of tumor cells that overexpress the Aurora kinases B and C.
ENMD-2076 is an orally-active, Aurora A/angiogenic kinase inhibitor with a unique kinase selectivity profile and multiple mechanisms of action. ENMD-2076 has been shown to inhibit a distinct profile of angiogenic tyrosine kinase targets in addition to the Aurora A kinase. Aurora kinases are key regulators of mitosis (cell division), and are often over-expressed in human cancers. ENMD-2076 also targets the VEGFR, Flt-3 and FGFR3 kinases which have been shown to play important roles in the pathology of several cancers.
Ilorasertib is a small molecule inhibitor that targets the Aurora kinase family, specifically Aurora A and B. It has shown promising results in preclinical studies and is currently being evaluated in clinical trials for the treatment of various types of cancer.
Hesperadin is a small molecule inhibitor that has gained significant attention in the field of scientific research due to its potential therapeutic applications. It is a selective inhibitor of Aurora B kinase, a protein kinase that plays a crucial role in cell division and mitosis. Hesperadin has been shown to inhibit the proliferation of cancer cells and has been investigated as a potential treatment for various types of cancer. In addition, it has also been studied for its effects on cell function and signal transduction, as well as its potential applications in environmental and industrial research.
JH295 is a synthetic compound that has gained significant attention in the scientific community due to its potential therapeutic and environmental applications. This paper aims to provide a comprehensive review of JH295, including its method of synthesis or extraction, chemical structure and biological activity, biological effects, applications in medical, environmental, and industrial research, and future perspectives and challenges.