Information
INCB057643 INCB057643 is a BET inhibitor that binds to the acetylated lysine recognition motifs found in the BRD of BET proteins, thereby preventing the interaction between the BET proteins and acetylated lysines on histones.
Targets
BET
In vitro
INCB057643 inhibits binding of BRD2/BRD3/BRD4 to an acetylated histone H4 peptide in the low nM range, and is selective against other bromodomain containing proteins. In vitro analyses show that INCB057643 inhibits proliferation of human AML, DLBCL, and multiple myeloma cell lines, with a corresponding decrease in MYC protein levels. Cell cycle analyses indicate that G1 arrest and a concentration-dependent increase in apoptosis are seen within 48 hours of treatment with INCB057643. Production of several cytokines, including IL-6, IL-10 and MIP-1α, was repressed by INCB057643 in human and mouse whole blood stimulated ex vivo with LPS. INCB057643 inhibits proliferation of prostate cancer cell lines. In short-term cell proliferation assays, INCB057643 appears more effective against androgen-dependent (VCaP and LNCaP) than androgen-independent (DU145 and PC3) cells.
In vivo
Oral administration of INCB057643 resulted in significant anti-tumor efficacy in xenograft models of AML, myeloma, and DLBCL. Treatment of mice bearing 22Rv1 tumor xenografts with INCB057643 (3 mg/kg) led to significant inhibition of tumor growth (T/C%:45%) and consistent reduction of tumor weight relative to vehicle-treated mice.
| ALogP | 1.114 |
|---|---|
| hba_count | 5 |
| HBD Count | 1 |
| Rotatable Bond | 2 |
| Canonical Smiles | CC1(C(=O)N(C2=CC(=CC(=C2O1)C3=CN(C(=O)C4=C3C=CN4)C)S(=O)(=O)C)C)C |
|---|---|
| IUPAC Name | 2,2,4-trimethyl-8-(6-methyl-7-oxo-1H-pyrrolo[2,3-c]pyridin-4-yl)-6-methylsulfonyl-1,4-benzoxazin-3-one |
| InChIKey | VZSAMEOETVNDQH-UHFFFAOYSA-N |
| INCHI | 1S/C20H21N3O5S/c1-20(2)19(25)23(4)15-9-11(29(5,26)27)8-13(17(15)28-20)14-10-22(3)18(24)16-12(14)6-7-21-16/h6-10,21H,1-5H3 |
| Isomeric SMILES | CC1(C(=O)N(C2=CC(=CC(=C2O1)C3=CN(C(=O)C4=C3C=CN4)C)S(=O)(=O)C)C)C |
| Molecular Weight | 415.46 |
| Reaxy-Rn | 32166087 |
| Reaxys-RN_link_address | https://www.reaxys.com/reaxys/secured/hopinto.do?context=S&query=IDE.XRN=32166087&ln= |
Comprehensive hazard, handling, storage, and regulatory compliance document.
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View spec sheet →Taxonomy Tree
| Kingdom | Organic compounds |
|---|---|
| Superclass | Organoheterocyclic compounds |
| Class | Benzoxazines |
| Subclass | Benzoxazinones |
| Intermediate Tree Nodes | Not available |
| Direct Parent | Benzoxazinones |
| Alternative Parents | Benzomorpholines Pyrrolopyridines Pyridinones Alkyl aryl ethers Benzenoids Tertiary carboxylic acid amides Sulfones Pyrroles Heteroaromatic compounds Lactams Oxacyclic compounds Azacyclic compounds Organopnictogen compounds Organonitrogen compounds Organic oxides Hydrocarbon derivatives Carbonyl compounds |
| Molecular Framework | Aromatic heteropolycyclic compounds |
| Substituents | Benzoxazinone - Benzomorpholine - Pyrrolopyridine - Pyridinone - Alkyl aryl ether - Benzenoid - Pyridine - Oxazinane - Heteroaromatic compound - Tertiary carboxylic acid amide - Sulfonyl - Sulfone - Pyrrole - Lactam - Carboxamide group - Oxacycle - Azacycle - Ether - Carboxylic acid derivative - Organic nitrogen compound - Organic oxygen compound - Organopnictogen compound - Organic oxide - Hydrocarbon derivative - Organosulfur compound - Organooxygen compound - Organonitrogen compound - Carbonyl group - Aromatic heteropolycyclic compound |
| Description | This compound belongs to the class of organic compounds known as benzoxazinones. These are organic compounds containing a benzene fused to an oxazine ring (a six-member aliphatic ring with four carbon atoms, one oxygen atom, and one nitrogen atom) bearing a ketone group. |
| External Descriptors | Not available |
| DMSO(mg / mL) Max Solubility | 83 |
|---|---|
| DMSO(mM) Max Solubility | 199.778558706013 |
| Water(mg / mL) Max Solubility | ＜1 |
| Molecular Weight | 415.500 g/mol |
| XLogP3 | 0.800 |
| Hydrogen Bond Donor Count | 1 |
| Hydrogen Bond Acceptor Count | 5 |
| Rotatable Bond Count | 2 |
| Exact Mass | 415.12 Da |
| Monoisotopic Mass | 415.12 Da |
| Topological Polar Surface Area | 108.000 Ų |
| Heavy Atom Count | 29 |
| Formal Charge | 0 |
| Complexity | 862.000 |
| Isotope Atom Count | 0 |
| Defined Atom Stereocenter Count | 0 |
| Undefined Atom Stereocenter Count | 0 |
| Defined Bond Stereocenter Count | 0 |
| Undefined Bond Stereocenter Count | 0 |
| The total count of all stereochemical bonds | 0 |
| Covalently-Bonded Unit Count | 1 |
