MOLIBRESIB BESYLATE

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C22H22ClN5O2.C6H6O3S
Molecular Weight	582.07
Optical Activity	UNSPECIFIED
Defined Stereocenters	1 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

OS(=O)(=O)C1=CC=CC=C1.CCNC(=O)C[C@@H]2N=C(C3=CC=C(Cl)C=C3)C4=CC(OC)=CC=C4N5C(C)=NN=C25

InChI

InChIKey=UQGMFOYDYUZADE-FERBBOLQSA-N

InChI=1S/C22H22ClN5O2.C6H6O3S/c1-4-24-20(29)12-18-22-27-26-13(2)28(22)19-10-9-16(30-3)11-17(19)21(25-18)14-5-7-15(23)8-6-14;7-10(8,9)6-4-2-1-3-5-6/h5-11,18H,4,12H2,1-3H3,(H,24,29);1-5H,(H,7,8,9)/t18-;/m0./s1

HIDE SMILES / InChI

Molecular Formula	C22H22ClN5O2
Molecular Weight	423.895
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	1 / 1
E/Z Centers	0
Optical Activity	UNSPECIFIED

Molecular Formula	C6H6O3S
Molecular Weight	158.175
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/21068722http://adisinsight.springer.com/drugs/800036177
Curator's Comment: Description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/21068722 | https://www.ncbi.nlm.nih.gov/pubmed/24015967

I-BET-762 (GSK 525762) is a small molecule benzodiazepine, by 'mimicking' acetylated histones interferes with the recognition of acetylated histones by BET family of bromodomains (BRD2, BRD3, and BRD4), which disrupts chromatin remodeling and gene expression. Prevention of the expression of certain growth-promoting genes may lead to an inhibition of tumour cell growth. GlaxoSmithKline is developing GSK 525762 for the oral treatment of solid tumours and haematological malignancies.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Bromodomain-containing protein 3 7 Target ID: CHEMBL1795186 Sources: https://www.ncbi.nlm.nih.gov/pubmed/21068722\|https://www.ncbi.nlm.nih.gov/pubmed/24015967	Inhibitor 8297	42.4 nM [IC50]
Bromodomain-containing protein 2 7 Target ID: CHEMBL1293289 Sources: https://www.ncbi.nlm.nih.gov/pubmed/21568322	Inhibitor 8297	32.5 nM [IC50]
Bromodomain-containing protein 4 13 Target ID: CHEMBL1163125 Sources: https://www.ncbi.nlm.nih.gov/pubmed/21568322	Inhibitor 8297	36.1 nM [IC50]
Bromodomain-containing protein 4 13 Target ID: CHEMBL1163125 Sources: https://www.ncbi.nlm.nih.gov/pubmed/21068722 \| https://www.ncbi.nlm.nih.gov/pubmed/24015967	Inhibitor 8297
Bromodomain-containing protein 2 7 Target ID: CHEMBL1293289 Sources: https://www.ncbi.nlm.nih.gov/pubmed/21068722 \| https://www.ncbi.nlm.nih.gov/pubmed/24015967	Inhibitor 8297
Bromodomain-containing protein 3 7 Target ID: CHEMBL1795186 Sources: https://www.ncbi.nlm.nih.gov/pubmed/21068722 \| https://www.ncbi.nlm.nih.gov/pubmed/24015967	Inhibitor 8297

Conditions

Condition	Modality	Highest Phase	Product
NUT midline carcinoma 2 Sources: http://adisinsight.springer.com/drugs/800036177	Primary	Phase II 1132	Unknown Approved Use Unknown
Breast cancer 434 Sources: http://adisinsight.springer.com/drugs/800036177	Primary	Phase II 1132	Unknown Approved Use Unknown
Acute myeloid leukemia 136 Sources: http://adisinsight.springer.com/drugs/800036177	Primary	Phase II 1132	Unknown Approved Use Unknown
Non-Hodgkin's lymphoma 79 Sources: http://adisinsight.springer.com/drugs/800036177	Primary	Phase II 1132	Unknown Approved Use Unknown
Multiple myeloma 159 Sources: http://adisinsight.springer.com/drugs/800036177	Primary	Phase II 1132	Unknown Approved Use Unknown
Unknown 2578

C_max

Value	Dose	Co-administered	Analyte	Population
918.6 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/32328561	100 mg 1 times / day multiple, oral dose: 100 mg route of administration: Oral experiment type: MULTIPLE co-administered:		GSK-525762 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
1080.5 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/32328561	100 mg 1 times / day single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:		GSK-525762 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
3818.5 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/32328561	100 mg 1 times / day multiple, oral dose: 100 mg route of administration: Oral experiment type: MULTIPLE co-administered:		GSK-525762 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
7294.6 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/32328561	100 mg 1 times / day single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:		GSK-525762 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
3.82 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/32328561	100 mg 1 times / day multiple, oral dose: 100 mg route of administration: Oral experiment type: MULTIPLE co-administered:		GSK-525762 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
6.2 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/32328561	100 mg 1 times / day single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:		GSK-525762 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

PubMed

Title	Date	PubMed
Suppression of inflammation by a synthetic histone mimic.	2010 Dec 23	21068722
Liver X receptors as regulators of macrophage inflammatory and metabolic pathways.	2011 Aug	21193033
Discovery and characterization of small molecule inhibitors of the BET family bromodomains.	2011 Jun 9	21568322
Selective inhibition of CD4+ T-cell cytokine production and autoimmunity by BET protein and c-Myc inhibitors.	2012 Sep 4	22912406
Discovery of epigenetic regulator I-BET762: lead optimization to afford a clinical candidate inhibitor of the BET bromodomains.	2013 Oct 10	24015967
The making of I-BET762, a BET bromodomain inhibitor now in clinical development.	2013 Oct 10	24107192
Potent antimyeloma activity of the novel bromodomain inhibitors I-BET151 and I-BET762.	2014 Jan 30	24335499
An epigenomic approach to therapy for tamoxifen-resistant breast cancer.	2014 Jul	24874954
BET inhibitor resistance emerges from leukaemia stem cells.	2015 Sep 24	26367796
CCAT1 is an enhancer-templated RNA that predicts BET sensitivity in colorectal cancer.	2016 Feb	26752646

Patents

Sample Use Guides

In Vivo Use Guide

Unknown

Route of Administration: Unknown

In Vitro Use Guide

Unknown

Substance Class	Chemical Created by `admin` on `Sat Dec 16 14:07:26 GMT 2023` Edited by `admin` on `Sat Dec 16 14:07:26 GMT 2023`
Record UNII	K04D7I4BCH
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

MOLIBRESIB BESYLATE

Official Name

English

GSK525762C

Code

English

2-[(4S)-6-(4-Chlorophenyl)-8-methoxy-1-methyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-4-yl]-N-ethylacetamide monobenzenesulfonate salt

Systematic Name

English

GSK-525762C

Code

English

MOLIBRESIB BESYLATE [USAN]

Common Name

English

4H-(1,2,4)TRIAZOLO(4,3-A)(1,4)BENZODIAZEPINE-4-ACETAMIDE, 6-(4-CHLOROPHENYL)-N-ETHYL-8-METHOXY-1-METHYL-, (4S)-, COMPD. WITH BENZENESULFONATE (1:1)

Systematic Name

English

Code System Code Type Description

CAS

1895049-20-3