1260907-17-2 Usage
Description
GSK 525762A, also known as I-BET762, is a synthetic compound belonging to the class of BET Bromodomain Inhibitors. It is currently in clinical development and has shown potential in the treatment of various medical conditions, including cancers and inflammatory diseases. The compound interacts with BET proteins, such as BRD2, BRD3, and BRD4, with high affinity, blocking their binding to acetylated histones and disrupting the formation of chromatin complexes involved in the expression of specific inflammatory genes.
Uses
Used in Pharmaceutical Industry:
GSK 525762A is used as a therapeutic agent for the treatment of cancers. It modulates the expression of specific genes by inhibiting the interaction between BET proteins and acetylated histones, thereby disrupting the formation of chromatin complexes involved in cancer development and progression.
Used in Inflammatory Disease Treatment:
GSK 525762A is used as an anti-inflammatory agent, providing protection against bacteria-induced sepsis and lipopolysaccharide-triggered endotoxic shock. By blocking the binding of BET proteins with acetylated histones, it disrupts the formation of chromatin complexes involved in the expression of specific inflammatory genes in activated macrophages, reducing inflammation and its associated complications.
Used in Drug Development Research:
GSK 525762A serves as a valuable research tool for studying the role of BET proteins in various biological processes, including gene expression, cell signaling, and disease development. It helps researchers understand the molecular mechanisms underlying the pathogenesis of cancers and inflammatory diseases, paving the way for the development of novel therapeutic strategies and targeted drug candidates.
Biochem/physiol Actions
I-BET762 possesses anti-inflammatory property by controlling the pro-inflammatory gene expression. I-BET762 hinders the MYC (proto-oncogene) expression in cellular models. This action of I-BET762 might serve as an effective therapy in treating prostate cancer.
References
1) Nicodeme?et al.?(2010),?Suppression of inflammation by a synthetic histone mimic; Nature?468?1119
2) Mirguet?et al.?(2013),?Discovery of Epigenetic Regulator I-BET762: Lead Optimization to Afford a Clinical Candidate Inhibitor of the BET Bromodomains; J. Med. Chem.,?56?7501
3) Bandukwala?et al.?(2012),?Selective inhibition of CD4+ T-cell cytokine production and autoimmunity by BET protein and c-Myc inhibitors; Proc. Natl. Acad. Sci. USA,?109?14532
4) Delmore?et al.?(2011),?BET Bromodomain as a Therapeutic Strategy to Target c-Myc; Cell?146?904
Check Digit Verification of cas no
The CAS Registry Mumber 1260907-17-2 includes 10 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 7 digits, 1,2,6,0,9,0 and 7 respectively; the second part has 2 digits, 1 and 7 respectively.
Calculate Digit Verification of CAS Registry Number 1260907-17:
(9*1)+(8*2)+(7*6)+(6*0)+(5*9)+(4*0)+(3*7)+(2*1)+(1*7)=142
142 % 10 = 2
So 1260907-17-2 is a valid CAS Registry Number.
1260907-17-2Relevant articles and documents
Preparation of Methyltriazolo[1,4]benzodiazepine via Oxidative Activation of a Thiolactam for the Synthesis of BET Inhibitor Molibresib
Erickson, Greg A.,Hatcher, Mark A.,Journet, Michel,Kowalski, John A.,Lovelace, Tom C.,Pink, Christopher J.,Xie, Shiping
, (2021/05/29)
A novel oxidative activation of a thiolactam was developed for the preparation of methyltriazolo[1,4]benzodiazepine in a single step. A sulfenic acid (R-SOH) was proposed as the activated intermediate with the concurrent formation of acetylhydrazone from acethydrazide and cyclocondensation to the triazole. A version of the method with 35% peracetic acid was scaled up to 40 kg as a part of the new route for the synthesis of BET inhibitor molibresib (GSK525762). The thiolactam was prepared from commercially available (2-amino-5-methoxyphenyl)(4-chlorophenyl)methanone in two steps in 66% yield. The concise four-step synthesis delivered 52 kg of molibresib of >99.9% ee in an overall 41% yield from the ketone. The condition for the methyltriazole was mild and free of racemization of the sensitive stereocenter. The oxidative method, with several advantages to the known methods, should be applicable to the synthesis of alkyltriazoles from other thiolactams and acylhydrazines.
Discovery of epigenetic regulator i-bet762: Lead optimization to afford a clinical candidate inhibitor of the bet bromodomains
Mirguet, Olivier,Gosmini, Romain,Toum, Jéro?me,Clément, Catherine A.,Barnathan, Mélanie,Brusq, Jean-Marie,Mordaunt, Jacqueline E.,Grimes, Richard M.,Crowe, Miriam,Pineau, Olivier,Ajakane, Myriam,Daugan, Alain,Jeffrey, Phillip,Cutler, Leanne,Haynes, Andrea C.,Smithers, Nicholas N.,Chung, Chun-Wa,Bamborough, Paul,Uings, Iain J.,Lewis, Antonia,Witherington, Jason,Parr, Nigel,Prinjha, Rab K.,Nicodème, Edwige
, p. 7501 - 7515 (2013/11/06)
The bromo and extra C-terminal domain (BET) family of bromodomains are involved in binding epigenetic marks on histone proteins, more specifically acetylated lysine residues. This paper describes the discovery and structure-activity relationships (SAR) of potent benzodiazepine inhibitors that disrupt the function of the BET family of bromodomains (BRD2, BRD3, and BRD4). This work has yielded a potent, selective compound I-BET762 that is now under evaluation in a phase I/II clinical trial for nuclear protein in testis (NUT) midline carcinoma and other cancers.
Bromodomain Inhibitors For Treating Autoimmune And Inflammatory Diseases
-
, (2012/08/28)
The use of compounds in the treatment of autoimmune and inflammatory diseases or conditions, pharmaceutical compositions containing such compounds and to methods for identifying compounds for use in the treatment of such diseases or conditions.
