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
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
Molecular Formula | C22H19F2N3O4S |
Molecular Weight | 459.466 |
Charge | 0 |
Count |
|
Stereochemistry | ACHIRAL |
Additional Stereochemistry | No |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 0 |
Optical Activity | NONE |
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.
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
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Target ID: O60885 Gene ID: 23476.0 Gene Symbol: BRD4 Target Organism: Homo sapiens (Human) |
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Target ID: P25440|||Q63HQ9 Gene ID: 6046.0 Gene Symbol: BRD2 Target Organism: Homo sapiens (Human) |
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Target ID: Q15059 Gene ID: 8019.0 Gene Symbol: BRD3 Target Organism: Homo sapiens (Human) |
12.2 nM [Kd] |
PubMed
Title | Date | PubMed |
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Preclinical Characterization of BET Family Bromodomain Inhibitor ABBV-075 Suggests Combination Therapeutic Strategies. | 2017 Jun 1 |
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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
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
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
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admin
on
Edited
Sat Dec 16 16:22:26 GMT 2023
by
admin
on
Sat Dec 16 16:22:26 GMT 2023
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Record UNII |
VR86R11J7J
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Record Status |
Validated (UNII)
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C274
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Related Record | Type | Details | ||
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TARGET -> INHIBITOR |
BINDING
Ki
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METABOLIC ENZYME -> SUBSTRATE |
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TARGET -> INHIBITOR |
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Ki
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TARGET -> INHIBITOR |
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Ki
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ACTIVE MOIETY |