U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

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 of MOLIBRESIB

SMILES

CCNC(=O)C[C@@H]1N=C(C2=CC=C(Cl)C=C2)C3=CC(OC)=CC=C3N4C(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
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

Unknown
139594
Targets

Targets

Primary TargetPharmacologyConditionPotency
Inhibitor
8297
 42.4 nM [IC50]
Inhibitor
8297
 32.5 nM [IC50]
Inhibitor
8297
 36.1 nM [IC50]
Inhibitor
8297
Inhibitor
8297
Inhibitor
8297
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Phase II
1132
Unknown

Approved Use

Unknown
Primary
Phase II
1132
Unknown

Approved Use

Unknown
Primary
Phase II
1132
Unknown

Approved Use

Unknown
Primary
Phase II
1132
Unknown

Approved Use

Unknown
Primary
Phase II
1132
Unknown

Approved Use

Unknown
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
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

AUC

ValueDoseCo-administeredAnalytePopulation
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
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
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

PubMed

TitleDatePubMed
Suppression of inflammation by a synthetic histone mimic.
2010 Dec 23
Liver X receptors as regulators of macrophage inflammatory and metabolic pathways.
2011 Aug
Selective inhibition of CD4+ T-cell cytokine production and autoimmunity by BET protein and c-Myc inhibitors.
2012 Sep 4
An epigenomic approach to therapy for tamoxifen-resistant breast cancer.
2014 Jul
BET inhibitor resistance emerges from leukaemia stem cells.
2015 Sep 24
CCAT1 is an enhancer-templated RNA that predicts BET sensitivity in colorectal cancer.
2016 Feb
Patents

Patents

EP-3050885-A1
2
US-9102677-B2
2
WO2015049629A1
2
WO2016014859A1
2
WO2016196065A1
2

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 01:27:20 GMT 2023
Edited
by admin
on Sat Dec 16 01:27:20 GMT 2023
Record UNII
5QIO6SRZ2R
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
MOLIBRESIB
INN  
USAN   INN  
Official Name English
GSK525762
Code English
I-BET 762
Code English
GSK525762A
Code English
molibresib [INN]
Common Name English
GSK-525762A
Code 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
Created by admin on Sat Dec 16 01:27:20 GMT 2023 , Edited by admin on Sat Dec 16 01:27:20 GMT 2023
Code System Code Type Description
EPA CompTox
DTXSID60677590
Created by admin on Sat Dec 16 01:27:20 GMT 2023 , Edited by admin on Sat Dec 16 01:27:20 GMT 2023
PRIMARY
USAN
FG-34
Created by admin on Sat Dec 16 01:27:21 GMT 2023 , Edited by admin on Sat Dec 16 01:27:21 GMT 2023
PRIMARY
PUBCHEM
46943432
Created by admin on Sat Dec 16 01:27:20 GMT 2023 , Edited by admin on Sat Dec 16 01:27:20 GMT 2023
PRIMARY
INN
10533
Created by admin on Sat Dec 16 01:27:20 GMT 2023 , Edited by admin on Sat Dec 16 01:27:20 GMT 2023
PRIMARY
FDA UNII
5QIO6SRZ2R
Created by admin on Sat Dec 16 01:27:20 GMT 2023 , Edited by admin on Sat Dec 16 01:27:20 GMT 2023
PRIMARY
SMS_ID
100000175234
Created by admin on Sat Dec 16 01:27:20 GMT 2023 , Edited by admin on Sat Dec 16 01:27:20 GMT 2023
PRIMARY
NCI_THESAURUS
C101538
Created by admin on Sat Dec 16 01:27:20 GMT 2023 , Edited by admin on Sat Dec 16 01:27:20 GMT 2023
PRIMARY
CAS
1260907-17-2
Created by admin on Sat Dec 16 01:27:20 GMT 2023 , Edited by admin on Sat Dec 16 01:27:20 GMT 2023
PRIMARY
Related Record Type Details
BROMODOMAIN-CONTAINING PROTEIN 2
TARGET -> INHIBITOR
Kd
Structure of MOLIBRESIB BESYLATE
SALT/SOLVATE -> PARENT
BROMODOMAIN-CONTAINING PROTEIN 4
TARGET -> INHIBITOR
BROMODOMAIN-CONTAINING PROTEIN 3
TARGET -> INHIBITOR
Kd
Related Record Type Details
Structure of MOLIBRESIB
ACTIVE MOIETY
NIH
NCATS
PRIVACY ACT
ACCESSIBILITY
DISCLAIMER
HHS VULNERABILITY DISCLOSURE
For language access assistance, contact the NCATS Public Information Officer
National Center for Advancing Translational Sciences (NCATS),
6701 Democracy Boulevard, Bethesda MD 20892-4874 • 301-594-8966