1300031-52-0 Usage
Description
GSK1324726A (I-BET726) is a potent inhibitor of BET family proteins, specifically targeting BRD2, BRD3, and BRD4 with high affinity. It competes with tetra-acetylated histone 4 peptides for binding to the bromodomains of these proteins, demonstrating over 1,000-fold selectivity for these proteins compared to other bromodomain-containing homologs. I-BET726 has the ability to inhibit cell growth and induce cytotoxicity in neuroblastoma cell lines by modulating the expression of genes involved in apoptosis and Myc signaling. It can be administered orally to animals and has been shown to reduce tumor growth in mouse xenograft models of human neuroblastoma.
Uses
Used in Pharmaceutical Industry:
GSK1324726A (I-BET726) is used as an anticancer agent for the treatment of neuroblastoma, a type of cancer commonly characterized by the overexpression of BET proteins. It modulates the expression of genes involved in apoptosis and Myc signaling, leading to the inhibition of cell growth and induction of cytotoxicity in neuroblastoma cell lines.
Used in Drug Development Research:
In the field of drug development, GSK1324726A (I-BET726) serves as a valuable research tool for studying the role of BET proteins in various diseases, particularly cancer. Its high selectivity and affinity for BRD2, BRD3, and BRD4 make it an ideal candidate for investigating the therapeutic potential of bromodomain inhibition in different pathological conditions.
Used in Preclinical Cancer Models:
GSK1324726A (I-BET726) is used in preclinical cancer models, specifically mouse xenograft models of human neuroblastoma, to evaluate its efficacy in reducing tumor growth. This helps researchers understand the potential of I-BET726 as a therapeutic agent and its impact on cancer progression.
Used in Drug Screening and Compound Libraries:
In the context of drug screening and compound libraries, GSK1324726A (I-BET726) is utilized to identify and develop novel bromodomain inhibitors with improved potency, selectivity, and pharmacological properties. This contributes to the advancement of therapeutic strategies targeting BET proteins in various diseases, including cancer.
references
[1] wyce a, ganji g, smitheman kn, chung cw, korenchuk s, bai y, barbash o, le b, craggs pd, mccabe mt, kennedy-wilson km, sanchez lv, gosmini rl, parr n, mchugh cf, dhanak d, prinjha rk, auger kr, tummino pj. bet inhibition silences expression of mycn and bcl2 and induces cytotoxicity in neuroblastoma tumor models. plos one. 2013 aug 23;8(8):e72967.
Check Digit Verification of cas no
The CAS Registry Mumber 1300031-52-0 includes 10 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 7 digits, 1,3,0,0,0,3 and 1 respectively; the second part has 2 digits, 5 and 2 respectively.
Calculate Digit Verification of CAS Registry Number 1300031-52:
(9*1)+(8*3)+(7*0)+(6*0)+(5*0)+(4*3)+(3*1)+(2*5)+(1*2)=60
60 % 10 = 0
So 1300031-52-0 is a valid CAS Registry Number.
1300031-52-0Relevant articles and documents
NOVEL PROCESS
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, (2015/12/31)
A compound or a pharmaceutically acceptable salt or solvate thereof with a molecular weight in the range 100 to 750 which inhibits the binding of the first and/or second bromodomains of human BRD-2 to 4 to acetylated lysine residues of their physiological partner which is able to: a) form a hydrogen bonding interaction in which the compound accepts a hydrogen bond from the sidechain NH2 group of the asparagine residue found at: or b) accept a water-mediated hydrogen bond in which the compound accepts a hydrogen bond from a water that is itself hydrogen-bonded to the sidechain hydroxyl of the tyrosine residue found at and c) which are also able to form a Van der Waals interaction with a lipophilic binding region of a binding pocket such that one or more heavy atoms of the said compounds lie within a 5A range of any of the heavy atoms of the following bromodomain residues which define the binding pocket: for use in the treatment of chronic autoimmune and inflammatory conditions, acute inflammatory conditions or cancer.
The discovery of I-BET726 (GSK1324726A), a potent tetrahydroquinoline ApoA1 up-regulator and selective BET bromodomain inhibitor
Gosmini, Romain,Nguyen, Van Loc,Toum, Jér?me,Simon, Christophe,Brusq, Jean-Marie G.,Krysa, Gael,Mirguet, Olivier,Riou-Eymard, Alizon M.,Boursier, Eric V.,Trottet, Lionel,Bamborough, Paul,Clark, Hugh,Chung, Chun-Wa,Cutler, Leanne,Demont, Emmanuel H.,Kaur, Rejbinder,Lewis, Antonia J.,Schilling, Mark B.,Soden, Peter E.,Taylor, Simon,Walker, Ann L.,Walker, Matthew D.,Prinjha, Rab K.,Nicodème, Edwige
, p. 8111 - 8131 (2014/12/10)
Through their function as epigenetic readers of the histone code, the BET family of bromodomain-containing proteins regulate expression of multiple genes of therapeutic relevance, including those involved in tumor cell growth and inflammation. BET bromodomain inhibitors have profound antiproliferative and anti-inflammatory effects which translate into efficacy in oncology and inflammation models, and the first compounds have now progressed into clinical trials. The exciting biology of the BETs has led to great interest in the discovery of novel inhibitor classes. Here we describe the identification of a novel tetrahydroquinoline series through up-regulation of apolipoprotein A1 and the optimization into potent compounds active in murine models of septic shock and neuroblastoma. At the molecular level, these effects are produced by inhibition of BET bromodomains. X-ray crystallography reveals the interactions explaining the structure-activity relationships of binding. The resulting lead molecule, I-BET726, represents a new, potent, and selective class of tetrahydroquinoline-based BET inhibitors.
TETRAHYDROQUINOLINE DERIVATIVES USEFUL AS BROMODOMAIN INHIBITORS
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, (2012/11/07)
Tetrahydroquinoline compounds (I), pharmaceutical compositions containing such compounds and their use in therapy
