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

General Information of Drug (ID: DMNEB6J)

• Drug Name: PMID20855207C25 Drug Info
• Synonyms: GTPL8159; BDBM50329197

Indication

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

• Cross-matching ID:
  PubChem CID: 46868971
  TTD Drug ID: DMNEB6J

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

Drug(s) Targeting Aurora B messenger RNA (AURKB mRNA)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
PHA-739358	DMGYBZI	Prostate cancer	2C82.0	Phase 2	[12]
Indirubin-3'-monoxime	DMLRQH0	Discovery agent	N.A.	Investigative	[13]
SU 6656	DMF1P6W	Discovery agent	N.A.	Investigative	[14]
6-bromoindirubin-3-oxime	DM12WYV	Discovery agent	N.A.	Investigative	[13]
7-fluoroindirubin-3-oxime	DMQD34N	Discovery agent	N.A.	Investigative	[13]
PMID21742770C1	DME3JMH	Discovery agent	N.A.	Investigative	[15]
Indirubin-3-acetoxime	DM3UR1E	Discovery agent	N.A.	Investigative	[13]
CGP-57380	DMFPOUC	Discovery agent	N.A.	Investigative	[14]
Indirubin-3-methoxime	DMZ5ODC	Discovery agent	N.A.	Investigative	[13]
4-(1H-pyrazol-4-yl)-1H-pyrrolo[2,3-b]pyridine	DM9MPHF	Discovery agent	N.A.	Investigative	[16]

Drug(s) Targeting Aurora kinase C (AURKC)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
PHA-739358	DMGYBZI	Prostate cancer	2C82.0	Phase 2	[12]
ABT-348	DMMZOYN	Haematological malignancy	2B33.Y	Phase 2	[17]
HPP-607	DM5VSZR	Solid tumour/cancer	2A00-2F9Z	Phase 1	[18]
AMG 900	DMASGXJ	Solid tumour/cancer	2A00-2F9Z	Phase 1	[19]
SNS-314	DMAC5F2	Solid tumour/cancer	2A00-2F9Z	Phase 1	[20]
GSK1070916	DMXRPT6	Advanced solid tumour	2A00-2F9Z	Phase 1	[21]
GSK1070916A	DMCJUI9	Solid tumour/cancer	2A00-2F9Z	Phase 1	[21]
MK-6592	DMB5NOI	Solid tumour/cancer	2A00-2F9Z	Discontinued in Phase 1	[22]
Indirubin-3'-monoxime	DMLRQH0	Discovery agent	N.A.	Investigative	[13]
SU 6656	DMF1P6W	Discovery agent	N.A.	Investigative	[14]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Aurora B messenger RNA (AURKB mRNA)	TT9RTBL	AURKB_HUMAN	Inhibitor	[1]
Aurora kinase C (AURKC)	TTLYXIT	AURKC_HUMAN	Inhibitor	[1]
Checkpoint kinase-1 (CHK1)	TTTU902	CHK1_HUMAN	Inhibitor	[1]

References

• [1] Discovery of orally bioavailable imidazo[1,2-a]pyrazine-based Aurora kinase inhibitors. Bioorg Med Chem Lett. 2010 Nov 15;20(22):6739-43.
• [2] Characterization and preclinical development of LY2603618: a selective and potent Chk1 inhibitor. Invest New Drugs. 2014 Apr;32(2):213-26.
• [3] 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.
• [4] 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.
• [5] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [6] 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.
• [7] National Cancer Institute Drug Dictionary (drug id 730054).
• [8] Quantitative assessment of BCL-2:BIM complexes as a pharmacodynamic marker for venetoclax (ABT-199).
• [9] Clinical pipeline report, company report or official report of AstraZeneca (2009).
• [10] 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.
• [11] Cyclin-dependent kinase inhibitors for cancer therapy: a patent review (2009 - 2014).Expert Opin Ther Pat. 2015;25(9):953-70.
• [12] Potent and selective Aurora inhibitors identified by the expansion of a novel scaffold for protein kinase inhibition. J Med Chem. 2005 Apr 21;48(8):3080-4.
• [13] An integrated computational approach to the phenomenon of potent and selective inhibition of aurora kinases B and C by a series of 7-substituted in... J Med Chem. 2007 Aug 23;50(17):4027-37.
• [14] The selectivity of protein kinase inhibitors: a further update. Biochem J. 2007 Dec 15;408(3):297-315.
• [15] A Potent and Selective Quinoxalinone-Based STK33 Inhibitor Does Not Show Synthetic Lethality in KRAS-Dependent Cells. ACS Med Chem Lett. 2012 Dec 13;3(12):1034-1038.
• [16] Discovery of a new series of Aurora inhibitors through truncation of GSK1070916. Bioorg Med Chem Lett. 2010 Apr 15;20(8):2552-5.
• [17] Preclinical characterization of ABT-348, a kinase inhibitor targeting the aurora, vascular endothelial growth factor receptor/platelet-derived growth factor receptor, and Src kinase families. J Pharmacol Exp Ther. 2012 Dec;343(3):617-27.
• [18] URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 1936).
• [19] Preclinical evaluation of AMG 900, a novel potent and highly selective pan-aurora kinase inhibitor with activity in taxane-resistant tumor cell lines. Cancer Res. 2010 Dec 1;70(23):9846-54.
• [20] SNS-314, a pan-Aurora kinase inhibitor, shows potent anti-tumor activity and dosing flexibility in vivo. Cancer Chemother Pharmacol. 2010 Mar;65(4):707-17.
• [21] Discovery of GSK1070916, a potent and selective inhibitor of Aurora B/C kinase. J Med Chem. 2010 May 27;53(10):3973-4001.
• [22] Clinical experience with aurora kinase inhibitors: a review. Oncologist. 2009 Aug;14(8):780-93.