Details of the Drug

General Information of Drug (ID: DMG65CV)

Drug Name

INCB057643

Synonyms

INCB-057643; 1820889-23-3; UNII-87TZD0JEBS; 87TZD0JEBS; 2,2,4-trimethyl-8-(6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridin-4-yl)-6-(methylsulfonyl)-2H-benzo[b][1,4]oxazin-3(4H)-one; 2,2,4-Trimethyl-8-(6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo(2,3-C)pyridin-4-yl)-6-(methylsulfonyl)-2H-benzo(b)(1,4)oxazin-3(4H)-one; CHEMBL4594412; SCHEMBL17200525; US9957268, Example 75; BDBM391587; BCP29506; EX-A1908; NSC807398; s8714; NSC-807398; BS-16298; HY-111485; AK00799038; CS-0042192; INCB057643; INCB 057643; CC1(OC2=C(N(C1=O)C)C=C(C=C2C=2C1=C(C(N(C2)C)=O)NC=C1)S(=O)(=O)C)C; 2,2,4-trimethyl-8-(6-methyl-7- oxo-6,7-dihydro-1H- pyrrolo[2,3-c]pyridin-4-yl)-6- (methylsulfonyl)-2H-1,4- benzoxazin-3(4H)-one; 2H-1,4-Benzoxazin-3(4H)-one, 8-(6,7-dihydro-6-methyl-7-oxo-1H-pyrrolo(2,3-C)pyridin-4-yl)-2,2,4-trimethyl-6-(methylsulfonyl)-

Indication

Disease Entry	ICD 11	Status	REF
Solid tumour/cancer	2A00-2F9Z	Phase 1/2	[1]
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Drug Type

Small molecular drug

Structure

3D MOL

2D MOL

#Ro5 Violations (Lipinski): 0

Molecular Weight (mw)

415.5

Logarithm of the Partition Coefficient (xlogp)

0.8

Rotatable Bond Count (rotbonds)

Hydrogen Bond Donor Count (hbonddonor)

Hydrogen Bond Acceptor Count (hbondacc)

Chemical Identifiers

Formula: C20H21N3O5S
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
Canonical SMILES: CC1(C(=O)N(C2=CC(=CC(=C2O1)C3=CN(C(=O)C4=C3C=CN4)C)S(=O)(=O)C)C)C
InChI: 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
InChIKey: VZSAMEOETVNDQH-UHFFFAOYSA-N

Cross-matching ID

PubChem CID: 118467751
CAS Number: 1820889-23-3
TTD ID: D7FJQ3

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Bromodomain and extraterminal domain protein (BET)	TTE4BSY	NOUNIPROTAC	Inhibitor	[2]

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Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Induced myeloid leukemia cell differentiation protein Mcl-1 (MCL1)	OT2YYI1A	MCL1_HUMAN	Gene/Protein Processing	[3]
Insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1)	OT9G360P	IF2B1_HUMAN	Gene/Protein Processing	[4]
Myc proto-oncogene protein (MYC)	OTPV5LUK	MYC_HUMAN	Gene/Protein Processing	[3]
N-myc proto-oncogene protein (MYCN)	OTWD33K1	MYCN_HUMAN	Gene/Protein Processing	[4]
Phorbol-12-myristate-13-acetate-induced protein 1 (PMAIP1)	OTXEE550	APR_HUMAN	Gene/Protein Processing	[3]
Serine-protein kinase ATM (ATM)	OTQVOHLT	ATM_HUMAN	Post-Translational Modifications	[3]
Wee1-like protein kinase	OTOHEU0N	WEE1_HUMAN	Post-Translational Modifications	[3]

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Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This Drug

References

1	ClinicalTrials.gov (NCT02711137) Open-Label Safety and Tolerability Study of INCB057643 in Subjects With Advanced Malignancies. U.S. National Institutes of Health.
2	Development of 2 Bromodomain and Extraterminal Inhibitors With Distinct Pharmacokinetic and Pharmacodynamic Profiles for the Treatment of Advanced Malignancies. Clin Cancer Res. 2020 Mar 15;26(6):1247-1257.
3	The synergy of the XPO1 inhibitors combined with the BET inhibitor INCB057643 in high-grade B-cell lymphoma via downregulation of MYC expression. Sci Rep. 2023 Oct 29;13(1):18554. doi: 10.1038/s41598-023-45721-z.
4	IGF2BP1 induces neuroblastoma via a druggable feedforward loop with MYCN promoting 17q oncogene expression. Mol Cancer. 2023 May 29;22(1):88. doi: 10.1186/s12943-023-01792-0.