Details of the Drug-Related molecule(s) Interaction Atlas

General Information of Drug (ID: DMG65CV)

Drug Name

INCB057643 Drug Info

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]

Cross-matching ID

PubChem CID: 118467751
ChEBI ID: CHEMBL4594412
CAS Number: CAS 1820889-23-3
TTD Drug ID: DMG65CV

Molecule-Related Drug Atlas

Molecule Type:

DTT

DOT

Drug Status:

Clinical Trial Drug(s)

Approved Drug(s)

Download the Complete Related Drug List

Drug(s) Targeting Bromodomain and extraterminal domain protein (BET)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
CPI-0610	DMPXOYJ	Myelofibrosis	2A20.2	Phase 3	[5]
ZEN-3694	DM6VQTF	Prostate cancer	2C82.0	Phase 2	[6]
OTX-015	DMI8RG1	Acute myeloid leukaemia	2A60	Phase 1/2	[5]
BMS-986158	DM6LDI4	Solid tumour/cancer	2A00-2F9Z	Phase 1/2	[5]
INCB054329	DM7TZL0	Refractory hematologic malignancy	2A85.5	Phase 1/2	[7]
ODM-207	DMOKVJD	Solid tumour/cancer	2A00-2F9Z	Phase 1/2	[8]
(+)-JQ1	DM1CZSJ	Testicular cancer	2C80	Phase 1	[9]
GSK525762	DMPAWBN	Haematological malignancy	2B33.Y	Phase 1	[5]
PLX51107	DMXLHVW	Haematological malignancy	2B33.Y	Phase 1	[5]
BI 894999	DM7W5N2	Solid tumour/cancer	2A00-2F9Z	Phase 1	[5]
------------------------------------------------------------------------------------


⏷ Show the Full List of 10 Drug(s)

Drug(s) Affected By Myc proto-oncogene protein (MYC)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Estradiol	DMUNTE3	Acne vulgaris	ED80	Approved	[10]
Sertraline	DM0FB1J	Coronary heart disease	BA80.Z	Approved	[11]
Fulvestrant	DM0YZC6	Breast cancer	2C60-2C65	Approved	[12]
Gefitinib	DM15F0X	Colon adenocarcinoma		Approved	[13]
Hydrogen peroxide	DM1NG5W	Infectious disease	1A00-CA43.1	Approved	[14]
Selenium	DM25CGV	N. A.	N. A.	Approved	[15]
Ribavirin	DMEYLH9	Hepatitis C virus infection	1E51.1	Approved	[16]
Trametinib	DM2JGQ3	Melanoma	2C30	Approved	[17]
Sulindac	DM2QHZU	Acute myelogenous leukaemia	2A41	Approved	[18]
Methotrexate	DM2TEOL	Anterior urethra cancer		Approved	[19]
------------------------------------------------------------------------------------


⏷ Show the Full List of 10 Drug(s)

Drug(s) Affected By Serine-protein kinase ATM (ATM)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Cannabidiol	DM0659E	Dravet syndrome	8A61.11	Approved	[20]
Paromomycin	DM1AGXN	Amoebiasis	1A36	Approved	[21]
Hydrogen peroxide	DM1NG5W	Infectious disease	1A00-CA43.1	Approved	[22]
Etretinate	DM2CZFA	Keratosis	ED56	Approved	[23]
Quercetin	DM3NC4M	Obesity	5B81	Approved	[24]
Tretinoin	DM49DUI	Acne vulgaris	ED80	Approved	[25]
Remdesivir	DMBFZ6L	Coronavirus Disease 2019 (COVID-19)	1D6Y	Approved	[26]
Acetic Acid, Glacial	DM4SJ5Y	infection in the ear canal	AA0Y	Approved	[27]
Rifampicin	DM5DSFZ	Non-insulin dependent diabetes	5A11	Approved	[28]
Arsenic trioxide	DM61TA4	Acute lymphoblastic leukaemia	2A85	Approved	[29]
------------------------------------------------------------------------------------


⏷ Show the Full List of 10 Drug(s)

Drug(s) Affected By Phorbol-12-myristate-13-acetate-induced protein 1 (PMAIP1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Cannabidiol	DM0659E	Dravet syndrome	8A61.11	Approved	[30]
Hydrogen peroxide	DM1NG5W	Infectious disease	1A00-CA43.1	Approved	[31]
Nitric Oxide	DM1RBYG	Hypertension	BA00-BA04	Approved	[32]
Methotrexate	DM2TEOL	Anterior urethra cancer		Approved	[33]
Simvastatin	DM30SGU	Arteriosclerosis	BD40	Approved	[34]
Quercetin	DM3NC4M	Obesity	5B81	Approved	[35]
Troglitazone	DM3VFPD	Diabetic complication	5A2Y	Approved	[36]
Penicillamine	DM40EF6	Cystinuria	5C60.2	Approved	[37]
Tretinoin	DM49DUI	Acne vulgaris	ED80	Approved	[38]
Acetic Acid, Glacial	DM4SJ5Y	infection in the ear canal	AA0Y	Approved	[27]
------------------------------------------------------------------------------------


⏷ Show the Full List of 10 Drug(s)

Drug(s) Affected By Insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Fulvestrant	DM0YZC6	Breast cancer	2C60-2C65	Approved	[39]
Marinol	DM70IK5	Anorexia nervosa cachexia	6B80	Approved	[40]
Valproate	DMCFE9I	Epilepsy	8A60-8A68	Approved	[41]
Ivermectin	DMDBX5F	Intestinal strongyloidiasis due to nematode parasite	1F6B	Approved	[42]
Cupric Sulfate	DMP0NFQ	Fungal infection	1F29-1F2F	Approved	[43]
Cisplatin	DMRHGI9	Adenocarcinoma	2D40	Approved	[44]
Arsenic	DMTL2Y1	N. A.	N. A.	Approved	[45]
Acetaminophen	DMUIE76	Allergic rhinitis	CA08.0	Approved	[46]
Doxorubicin	DMVP5YE	Acute myelogenous leukaemia	2A41	Approved	[47]
Urethane	DM7NSI0	N. A.	N. A.	Phase 4	[48]
------------------------------------------------------------------------------------


⏷ Show the Full List of 10 Drug(s)

Molecular Interaction Atlas of This Drug

Molecular Interaction Atlas

Download the Complete Interaction Atlas for Visualization in Cytoscape

Drug Therapeutic Target (DTT)

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

------------------------------------------------------------------------------------

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1)	OT9G360P	IF2B1_HUMAN	Gene/Protein Processing	[3]
Myc proto-oncogene protein (MYC)	OTPV5LUK	MYC_HUMAN	Gene/Protein Processing	[4]
Phorbol-12-myristate-13-acetate-induced protein 1 (PMAIP1)	OTXEE550	APR_HUMAN	Gene/Protein Processing	[4]
Serine-protein kinase ATM (ATM)	OTQVOHLT	ATM_HUMAN	Post-Translational Modifications	[4]
Wee1-like protein kinase	OTOHEU0N	WEE1_HUMAN	Post-Translational Modifications	[4]

------------------------------------------------------------------------------------

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	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.
4	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.
5	Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
6	Clinical pipeline report, company report or official report of Zenith Epigenetics.
7	The Novel Bromodomain and Extraterminal Domain Inhibitor INCB054329 Induces Vulnerabilities in Myeloma Cells That Inform Rational Combination Strategies. Clin Cancer Res. 2019 Jan 1;25(1):300-311.
8	First-in-human Phase 1 open label study of the BET inhibitor ODM-207 in patients with selected solid tumours. Br J Cancer. 2020 Dec;123(12):1730-1736.
9	Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
10	Acetaminophen-induced proliferation of estrogen-responsive breast cancer cells is associated with increases in c-myc RNA expression and NF-kappaB activity. Toxicol Sci. 2002 Apr;66(2):233-43. doi: 10.1093/toxsci/66.2.233.
11	Sertraline induces endoplasmic reticulum stress in hepatic cells. Toxicology. 2014 Aug 1;322:78-88. doi: 10.1016/j.tox.2014.05.007. Epub 2014 May 24.
12	Estrogen regulation in human breast cancer cells of new downstream gene targets involved in estrogen metabolism, cell proliferation and cell transformation. J Mol Endocrinol. 2004 Apr;32(2):397-414.
13	ZD1839 induces p15INK4b and causes G1 arrest by inhibiting the mitogen-activated protein kinase/extracellular signal-regulated kinase pathway. Mol Cancer Ther. 2007 May;6(5):1579-87. doi: 10.1158/1535-7163.MCT-06-0814.
14	Arsenic suppresses gene expression in promyelocytic leukemia cells partly through Sp1 oxidation. Blood. 2005 Jul 1;106(1):304-10.
15	Selenite and selenomethionine promote HL-60 cell cycle progression. J Nutr. 2002 Apr;132(4):674-9. doi: 10.1093/jn/132.4.674.
16	Ribavirin augments doxorubicin's efficacy in human hepatocellular carcinoma through inhibiting doxorubicin-induced eIF4E activation. J Biochem Mol Toxicol. 2018 Jan;32(1). doi: 10.1002/jbt.22007. Epub 2017 Nov 7.
17	Combination small molecule MEK and PI3K inhibition enhances uveal melanoma cell death in a mutant GNAQ- and GNA11-dependent manner. Clin Cancer Res. 2012 Aug 15;18(16):4345-55. doi: 10.1158/1078-0432.CCR-11-3227. Epub 2012 Jun 25.
18	Novel detection and differential utilization of a c-myc transcriptional block in colon cancer chemoprevention. Cancer Res. 2002 Nov 1;62(21):6006-10.
19	The contribution of methotrexate exposure and host factors on transcriptional variance in human liver. Toxicol Sci. 2007 Jun;97(2):582-94.
20	Cannabidiol Induces Cell Cycle Arrest and Cell Apoptosis in Human Gastric Cancer SGC-7901 Cells. Biomolecules. 2019 Jul 25;9(8):302. doi: 10.3390/biom9080302.
21	Correction of ATM gene function by aminoglycoside-induced read-through of premature termination codons. Proc Natl Acad Sci U S A. 2004 Nov 2;101(44):15676-81. doi: 10.1073/pnas.0405155101. Epub 2004 Oct 21.
22	Pro-oxidant induced DNA damage in human lymphoblastoid cells: homeostatic mechanisms of genotoxic tolerance. Toxicol Sci. 2012 Aug;128(2):387-97. doi: 10.1093/toxsci/kfs152. Epub 2012 Apr 26.
23	Bexarotene activates the p53/p73 pathway in human cutaneous T-cell lymphoma. Br J Dermatol. 2009 Mar;160(3):519-26. doi: 10.1111/j.1365-2133.2008.08931.x. Epub 2008 Nov 25.
24	Multifaceted preventive effects of single agent quercetin on a human prostate adenocarcinoma cell line (PC-3): implications for nutritional transcriptomics and multi-target therapy. Med Oncol. 2011 Dec;28(4):1395-404. doi: 10.1007/s12032-010-9603-3. Epub 2010 Jul 2.
25	Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
26	An in vitro study on anti-carcinogenic effect of remdesivir in human ovarian cancer cells via generation of reactive oxygen species. Hum Exp Toxicol. 2022 Jan-Dec;41:9603271221089257. doi: 10.1177/09603271221089257.
27	Motexafin gadolinium and zinc induce oxidative stress responses and apoptosis in B-cell lymphoma lines. Cancer Res. 2005 Dec 15;65(24):11676-88.
28	Integrated analysis of rifampicin-induced microRNA and gene expression changes in human hepatocytes. Drug Metab Pharmacokinet. 2014;29(4):333-40.
29	Arsenic trioxide induces apoptosis in NB-4, an acute promyelocytic leukemia cell line, through up-regulation of p73 via suppression of nuclear factor kappa B-mediated inhibition of p73 transcription and prevention of NF-kappaB-mediated induction of XIAP, cIAP2, BCL-XL and survivin. Med Oncol. 2010 Sep;27(3):833-42. doi: 10.1007/s12032-009-9294-9. Epub 2009 Sep 10.
30	Inhibiting Heat Shock Proteins Can Potentiate the Cytotoxic Effect of Cannabidiol in Human Glioma Cells. Anticancer Res. 2015 Nov;35(11):5827-37.
31	Time series analysis of oxidative stress response patterns in HepG2: a toxicogenomics approach. Toxicology. 2013 Apr 5;306:24-34.
32	Apoptotic signaling pathways induced by nitric oxide in human lymphoblastoid cells expressing wild-type or mutant p53. Cancer Res. 2004 May 1;64(9):3022-9. doi: 10.1158/0008-5472.can-03-1880.
33	Methotrexate induces apoptosis through p53/p21-dependent pathway and increases E-cadherin expression through downregulation of HDAC/EZH2. Biochem Pharmacol. 2011 Feb 15;81(4):510-7. doi: 10.1016/j.bcp.2010.11.014. Epub 2010 Nov 27.
34	Statin-triggered cell death in primary human lung mesenchymal cells involves p53-PUMA and release of Smac and Omi but not cytochrome c. Biochim Biophys Acta. 2010 Apr;1803(4):452-67. doi: 10.1016/j.bbamcr.2009.12.005. Epub 2010 Jan 4.
35	Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
36	Adipogenic Effects and Gene Expression Profiling of Firemaster? 550 Components in Human Primary Preadipocytes. Environ Health Perspect. 2017 Sep 14;125(9):097013. doi: 10.1289/EHP1318.
37	D-Penicillamine targets metastatic melanoma cells with induction of the unfolded protein response (UPR) and Noxa (PMAIP1)-dependent mitochondrial apoptosis. Apoptosis. 2012 Oct;17(10):1079-94.
38	Comparison of the gene expression profiles of monocytic versus granulocytic lineages of HL-60 leukemia cell differentiation by DNA microarray analysis. Life Sci. 2003 Aug 15;73(13):1705-19. doi: 10.1016/s0024-3205(03)00515-0.
39	DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
40	THC exposure of human iPSC neurons impacts genes associated with neuropsychiatric disorders. Transl Psychiatry. 2018 Apr 25;8(1):89. doi: 10.1038/s41398-018-0137-3.
41	Stem cell transcriptome responses and corresponding biomarkers that indicate the transition from adaptive responses to cytotoxicity. Chem Res Toxicol. 2017 Apr 17;30(4):905-922.
42	Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
43	Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
44	Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
45	Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
46	Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
47	METTL14 promotes doxorubicin-induced cardiomyocyte ferroptosis by regulating the KCNQ1OT1-miR-7-5p-TFRC axis. Cell Biol Toxicol. 2023 Jun;39(3):1015-1035. doi: 10.1007/s10565-021-09660-7. Epub 2021 Oct 14.
48	Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.