MOLIBRESIB

Investigational

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C22H22ClN5O2
Molecular Weight	423.895
Optical Activity	UNSPECIFIED
Defined Stereocenters	1 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CCNC(=O)C[C@@H]1N=C(C2=CC=C(Cl)C=C2)C3=C(C=CC(OC)=C3)N4C(C)=NN=C14

InChI

InChIKey=AAAQFGUYHFJNHI-SFHVURJKSA-N

InChI=1S/C22H22ClN5O2/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/h5-11,18H,4,12H2,1-3H3,(H,24,29)/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

Description
Sources: http://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	Condition	Potency
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 8504
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 8504
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 8504

Conditions

Condition	Modality	Highest Phase	Product
NUT midline carcinoma 2 Sources: http://adisinsight.springer.com/drugs/800036177	Primary	Phase II 1147	Unknown Approved Use Unknown
Breast cancer 432 Sources: http://adisinsight.springer.com/drugs/800036177	Primary	Phase II 1147	Unknown Approved Use Unknown
Acute myeloid leukemia 141 Sources: http://adisinsight.springer.com/drugs/800036177	Primary	Phase II 1147	Unknown Approved Use Unknown
Non-Hodgkin's lymphoma 81 Sources: http://adisinsight.springer.com/drugs/800036177	Primary	Phase II 1147	Unknown Approved Use Unknown
Multiple myeloma 159 Sources: http://adisinsight.springer.com/drugs/800036177	Primary	Phase II 1147	Unknown Approved Use Unknown

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
CCAT1 is an enhancer-templated RNA that predicts BET sensitivity in colorectal cancer.	2016-02	26752646
BET inhibitor resistance emerges from leukaemia stem cells.	2015-09-24	26367796
An epigenomic approach to therapy for tamoxifen-resistant breast cancer.	2014-07	24874954
Potent antimyeloma activity of the novel bromodomain inhibitors I-BET151 and I-BET762.	2014-01-30	24335499
Discovery of epigenetic regulator I-BET762: lead optimization to afford a clinical candidate inhibitor of the BET bromodomains.	2013-10-10	24015967
The making of I-BET762, a BET bromodomain inhibitor now in clinical development.	2013-10-10	24107192
Selective inhibition of CD4+ T-cell cytokine production and autoimmunity by BET protein and c-Myc inhibitors.	2012-09-04	22912406
Liver X receptors as regulators of macrophage inflammatory and metabolic pathways.	2011-08	21193033
Discovery and characterization of small molecule inhibitors of the BET family bromodomains.	2011-06-09	21568322
Suppression of inflammation by a synthetic histone mimic.	2010-12-23	21068722

Patents

Sample Use Guides

In Vivo Use Guide

GSK 525762, at the 60-100 mg QD doses, resulted in partial responses in two patients at 15 and 23 weeks, respectively, and stable disease in four patients, according to data from 11 treated patients with NUT midline carcinoma, in a phase I/II study

Route of Administration: Oral

In Vitro Use Guide

125-500 nM I-BET-762 (GSK 525762) treatment differentially alters CD4+ T-cell cytokine production

Substance Class	Chemical Created by `admin` on `Mon Mar 31 20:51:07 GMT 2025` Edited by `admin` on `Mon Mar 31 20:51:07 GMT 2025`
Record UNII	5QIO6SRZ2R
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

GSK-525762A

Preferred Name

English

MOLIBRESIB

Official Name

English

GSK525762

Code

English

I-BET 762

Code

English

GSK525762A

Code

English

molibresib [INN]

Common Name

English

GSK-525762

Code

English

MOLIBRESIB [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)-

Systematic Name

English

BET INHIBITOR GSK525762

Common Name

English

Molibresib [WHO-DD]

Common Name

English

2-((4S)-6-(4-CHLOROPHENYL)-8-METHOXY-1-METHYL-4HBENZO(F)(1,2,4)TRIAZOLO(4,3-A)(1,4)DIAZEPIN-4-YL)-N-ETHYLACETAMIDE

Systematic Name

English

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

Systematic Name

English

Classification Tree Code System Code

NCI_THESAURUS

C128462