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Details

Stereochemistry ACHIRAL
Molecular Formula C22H19F2N3O4S
Molecular Weight 459.466
Optical Activity UNSPECIFIED
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of MIVEBRESIB

SMILES

CCS(=O)(=O)NC1=CC=C(OC2=CC=C(F)C=C2F)C(=C1)C3=CN(C)C(=O)C4=C3C=CN4

InChI

InChIKey=RDONXGFGWSSFMY-UHFFFAOYSA-N
InChI=1S/C22H19F2N3O4S/c1-3-32(29,30)26-14-5-7-19(31-20-6-4-13(23)10-18(20)24)16(11-14)17-12-27(2)22(28)21-15(17)8-9-25-21/h4-12,25-26H,3H2,1-2H3

HIDE SMILES / InChI

Molecular Formula C22H19F2N3O4S
Molecular Weight 459.466
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Description

Mivebresib (ABBV-075) is a small molecule Bromodomain and Extra-Terminal motif (BET) inhibitor being studied in a Phase 1 clinical trial in patients with advanced hematologic malignancies and solid tumors. Mivebresib binds to BRD4 with a Ki of 1.5 nM. Comprehensive preclinical characterization of ABBV-075 demonstrated broad activity across cell lines and tumor models, representing a variety of hematologic malignancies and solid tumor indications. In most cancer cell lines derived from solid tumors, ABBV-075 triggers prominent G1 cell-cycle arrest without extensive apoptosis. Consistent with its broad spectrum of activities in vitro, ABBV-075 has comparable or superior efficacies to standard of care agents in flank xenograft mouse models of non-small-cell and small cell lung cancers, pancreatic, breast, prostate, head & neck cancers, multiple myeloma, diffuse large B cell lymphoma and leukemia.

Originator

Approval Year

PubMed

PubMed

TitleDatePubMed
Discovery of N-(4-(2,4-Difluorophenoxy)-3-(6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridin-4-yl)phenyl)ethanesulfonamide (ABBV-075/Mivebresib), a Potent and Orally Available Bromodomain and Extraterminal Domain (BET) Family Bromodomain Inhibitor.
2017 Oct 26

Sample Use Guides

In Vivo Use Guide
The recommended phase 2 dose is 1.5 mg for the daily schedule, 2.5 mg for 4/7 and 3 mg for MWF.
Route of Administration: Oral
In Vitro Use Guide
ABBV-075 binds bromodomains of BRD2/4/T with similar affinities (Ki of 1-2.2 nM) and highly selective for 18 bromodomain proteins tested (Kd > 1 uM; more than 600-fold selectivity vs. BRD4), but exhibits roughly 10-fold weaker potency towards BRD3 (Ki of 12.2 nM) and has moderate activity towards CREBBP (Kd = 87 uM; 54-fold selectivity vs. BRD4).
Substance Class Chemical
Created
by admin
on Tue Oct 22 01:25:45 UTC 2019
Edited
by admin
on Tue Oct 22 01:25:45 UTC 2019
Record UNII
VR86R11J7J
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
MIVEBRESIB
INN   WHO-DD  
USAN   INN  
Official Name English
ETHANESULFONAMIDE, N-(4-(2,4-DIFLUOROPHENOXY)-3-(6,7-DIHYDRO-6-METHYL-7-OXO-1H-PYRROLO(2,3-C)PYRIDIN-4-YL)PHENYL)-
Systematic Name English
MIVEBRESIB [WHO-DD]
Common Name English
ABBV-075
Code English
N-(4-(2,4-DIFLUOROPHENOXY)-3-(6-METHYL-7-OXO-6,7-DIHYDRO- 1H-PYRROLO(2,3-C)PYRIDIN-4-YL)PHENYL)ETHANESULFONAMIDE
Systematic Name English
MIVEBRESIB [INN]
Common Name English
ABBV075
Code English
MIVEBRESIB [USAN]
Common Name English
Classification Tree Code System Code
NCI_THESAURUS C274
Created by admin on Tue Oct 22 01:25:45 UTC 2019 , Edited by admin on Tue Oct 22 01:25:45 UTC 2019
Code System Code Type Description
INN
10341
Created by admin on Tue Oct 22 01:25:45 UTC 2019 , Edited by admin on Tue Oct 22 01:25:45 UTC 2019
PRIMARY
CAS
1445993-26-9
Created by admin on Tue Oct 22 01:25:45 UTC 2019 , Edited by admin on Tue Oct 22 01:25:45 UTC 2019
PRIMARY
PUBCHEM
71600087
Created by admin on Tue Oct 22 01:25:45 UTC 2019 , Edited by admin on Tue Oct 22 01:25:45 UTC 2019
PRIMARY
Related Record Type Details
TARGET -> INHIBITOR
BINDING
Ki
TRANSPORTER -> SUBSTRATE
METABOLIC ENZYME -> SUBSTRATE
MAJOR
TARGET -> INHIBITOR
BINDING
Ki
TARGET -> INHIBITOR
BINDING
Ki
METABOLIC ENZYME -> SUBSTRATE
MAJOR
TRANSPORTER -> SUBSTRATE
Related Record Type Details
ACTIVE MOIETY