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Details

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

SHOW SMILES / InChI
Structure of MIVEBRESIB

SMILES

CCS(=O)(=O)NC1=CC(=C(OC2=C(F)C=C(F)C=C2)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
MOL RATIO 1 MOL RATIO (average)
Stereochemistry ACHIRAL
Additional Stereochemistry No
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

Targets

Primary TargetPharmacologyConditionPotency
12.2 nM [Kd]

PubMed

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
Record UNII
VR86R11J7J
Record Status Validated (UNII)
Record Version