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

General Information of Drug (ID: DMS3JCN)

• Drug Name: 3-(1H-Indol-2-yl)-1H-quinolin-2-one Drug Info
• Synonyms: 3-(1H-indol-2-yl)quinolin-2(1H)-one

Indication

Disease Entry	ICD 11	Status	REF
Discovery agent	N.A.	Investigative	[1]

• Cross-matching ID:
  PubChem CID: 5329371
  TTD Drug ID: DMS3JCN

Molecule-Related Drug Atlas

Drug(s) Targeting Checkpoint kinase-1 (CHK1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
LY2603618	DMCXRZF	Pancreatic cancer	2C10	Phase 2	[3]
UCN-01	DMUNJZB	Non-small-cell lung cancer	2C25.Y	Phase 2	[4]
SCH-900776	DM67EMK	Solid tumour/cancer	2A00-2F9Z	Phase 2	[5]
LY2606368	DM4XMF7	Ovarian cancer	2C73	Phase 2	[6]
LY2880070	DMADEHZ	Solid tumour/cancer	2A00-2F9Z	Phase 1/2	[7]
RG7741	DMK6P9J	Lymphoma	2A80-2A86	Phase 1	[8]
GDC-0425	DMDZ26X	Lymphoma	2A80-2A86	Phase 1	[9]
AZD7762	DM1FW0C	Solid tumour/cancer	2A00-2F9Z	Phase 1	[10]
MK-8776	DMAS1RB	Hodgkin lymphoma	2B30	Phase 1	[11]
Diamidothiazole derivative 1	DM02V5Q	N. A.	N. A.	Patented	[12]

Drug(s) Targeting Vascular endothelial growth factor receptor 2 (KDR)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Sorafenib	DMS8IFC	Hepatocellular carcinoma	2C12.02	Approved	[13]
Romiplostim	DM3U7SZ	Thrombocytopenia	3B64	Approved	[14]
Regorafenib	DMHSY1I	Metastatic colorectal cancer	2B91	Approved	[15]
Sunitinib	DMCBJSR	Gastrointestinal cancer	2C11	Approved	[16]
Axitinib	DMGVH6N	Renal cell carcinoma	2C90	Approved	[17]
Vandetanib	DMRICNP	Solid tumour/cancer	2A00-2F9Z	Approved	[18]
Pazopanib HCl	DM6U9CQ	Renal cell carcinoma	2C90	Approved	[19]
Cabozantinib	DMIYDT4	Thyroid cancer	2D10	Approved	[20]
Tivozanib	DMUKC5L	Renal cell carcinoma	2C90	Approved	[21]
Lenvatinib	DMB1IU4	Thyroid cancer	2D10	Approved	[22]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Checkpoint kinase-1 (CHK1)	TTTU902	CHK1_HUMAN	Inhibitor	[2]
Vascular endothelial growth factor receptor 2 (KDR)	TTUTJGQ	VGFR2_HUMAN	Inhibitor	[1]

References

• [1] Optimization of the indolyl quinolinone class of KDR (VEGFR-2) kinase inhibitors: effects of 5-amido- and 5-sulphonamido-indolyl groups on pharmaco... Bioorg Med Chem Lett. 2004 Jan 19;14(2):351-5.
• [2] Development of 6-substituted indolylquinolinones as potent Chek1 kinase inhibitors. Bioorg Med Chem Lett. 2006 Nov 15;16(22):5907-12.
• [3] Characterization and preclinical development of LY2603618: a selective and potent Chk1 inhibitor. Invest New Drugs. 2014 Apr;32(2):213-26.
• [4] Characterization of an inhibitory dynamic pharmacophore for the ERCC1-XPA interaction using a combined molecular dynamics and virtual screening app... J Mol Graph Model. 2009 Sep;28(2):113-30.
• [5] Targeting the replication checkpoint using SCH 900776, a potent and functionally selective CHK1 inhibitor identified via high content screening. Mol Cancer Ther. 2011 Apr;10(4):591-602.
• [6] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [7] A phase Ib study of oral Chk1 inhibitor LY2880070 in combination with gemcitabine in patients with advanced or metastatic cancer. Journal of Clinical Oncology 38, no. 15_suppl (May 20, 2020) 3581-3581.
• [8] National Cancer Institute Drug Dictionary (drug id 730054).
• [9] Quantitative assessment of BCL-2:BIM complexes as a pharmacodynamic marker for venetoclax (ABT-199).
• [10] Clinical pipeline report, company report or official report of AstraZeneca (2009).
• [11] Chk1 Inhibitor MK-8776 Restores the Sensitivity of Chemotherapeutics in P-glycoprotein Overexpressing Cancer Cells. Int J Mol Sci. 2019 Aug 22;20(17):4095.
• [12] Cyclin-dependent kinase inhibitors for cancer therapy: a patent review (2009 - 2014).Expert Opin Ther Pat. 2015;25(9):953-70.
• [13] Preclinical overview of sorafenib, a multikinase inhibitor that targets both Raf and VEGF and PDGF receptor tyrosine kinase signaling.Mol Cancer Ther.2008 Oct;7(10):3129-40.
• [14] Anthranilic acid amides: a novel class of antiangiogenic VEGF receptor kinase inhibitors. J Med Chem. 2002 Dec 19;45(26):5687-93.
• [15] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [16] 2006 drug approvals: finding the niche. Nat Rev Drug Discov. 2007 Feb;6(2):99-101.
• [17] Nat Rev Drug Discov. 2013 Feb;12(2):87-90.
• [18] A comparison of physicochemical property profiles of marketed oral drugs and orally bioavailable anti-cancer protein kinase inhibitors in clinical development. Curr Top Med Chem. 2007;7(14):1408-22.
• [19] Hughes B: 2009 FDA drug approvals. Nat Rev Drug Discov. 2010 Feb;9(2):89-92.
• [20] Clinical pipeline report, company report or official report of Exelixis (2011).
• [21] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services
• [22] Emerging drugs for ovarian cancer. Expert Opin Emerg Drugs. 2008 Sep;13(3):523-36.