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

General Information of DTT (ID: TTTU902)

• DTT Name: Checkpoint kinase-1 (CHK1) DTT Info
• UniProt ID: CHK1_HUMAN
• Gene Name: CHEK1

Molecule-Related Drug & Molecule List

9 Clinical Trial Drug(s) Transported by This DTP

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
LY2603618	DMCXRZF	Pancreatic cancer	2C10	Phase 2	[1]
LY2606368	DM4XMF7	Ovarian cancer	2C73	Phase 2	[2], [3]
SCH-900776	DM67EMK	Solid tumour/cancer	2A00-2F9Z	Phase 2	[4]
UCN-01	DMUNJZB	Non-small-cell lung cancer	2C25.Y	Phase 2	[5], [6], [7], [8], [9]
LY2880070	DMADEHZ	Solid tumour/cancer	2A00-2F9Z	Phase 1/2	[10]
AZD7762	DM1FW0C	Solid tumour/cancer	2A00-2F9Z	Phase 1	[11]
GDC-0425	DMDZ26X	Lymphoma	2A80-2A86	Phase 1	[12]
MK-8776	DMAS1RB	Hodgkin lymphoma	2B30	Phase 1	[13]
RG7741	DMK6P9J	Lymphoma	2A80-2A86	Phase 1	[14], [15]

1 Patented Agent(s) Transported by This DTP

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Diamidothiazole derivative 1	DM02V5Q	N. A.	N. A.	Patented	[16]

3 Discontinued Drug(s) Transported by This DTP

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
PF-477736	DMDOTW0	Advanced solid tumour	2A00-2F9Z	Discontinued in Phase 1	[17]
RG7602	DMXJAFC	Lymphoma	2A80-2A86	Discontinued in Phase 1	[18]
XL844	DMHTG38	Solid tumour/cancer	2A00-2F9Z	Discontinued in Phase 1	[19]

33 Investigative Drug(s) Transported by This DTP

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
2-(1H-indazol-3-yl)-1H-benzo[d]imidazole	DM0CSH8	Discovery agent	N.A.	Investigative	[20]
2-(cyclohexylamino)benzoic acid	DMPT0MB	Discovery agent	N.A.	Investigative	[20]
3-(1H-Indol-2-yl)-1H-quinolin-2-one	DMS3JCN	Discovery agent	N.A.	Investigative	[21]
4,5,6,7-tetrabromo-1H-benzo[d][1,2,3]triazole	DMN9YOB	Discovery agent	N.A.	Investigative	[22]
4-[(3,5-diamino-1H-pyrazol-4-yl)diazenyl]phenol	DMSKJ1X	Discovery agent	N.A.	Investigative	[23]
6-(3-aminopropyl)benzo[h]isoquinolin-1(2H)-one	DMYA4D2	Discovery agent	N.A.	Investigative	[24]
6-MORPHOLIN-4-YL-9H-PURINE	DMTNZKU	Discovery agent	N.A.	Investigative	[20]
9-chlorobenzo[h]isoquinolin-1(2H)-one	DM6EFN2	Discovery agent	N.A.	Investigative	[24]
9-hydroxypyrrolo[3,4-c]carbazole-1,3(2H,6H)-dione	DMGCX7E	Discovery agent	N.A.	Investigative	[25]
A-432411	DMQHKIA	Discovery agent	N.A.	Investigative	[26]
ARRY-575	DMIRTF5	Solid tumour/cancer	2A00-2F9Z	Investigative	[27]
BIS-IMIDE A	DM0MK6D	Discovery agent	N.A.	Investigative	[28]
Bisindolylmaleimide-I	DMOQJZC	Discovery agent	N.A.	Investigative	[29]
BX-795	DMRIMLJ	Discovery agent	N.A.	Investigative	[30]
BX-912	DMZA45C	Discovery agent	N.A.	Investigative	[30]
CCT244747	DMSDH3A	Discovery agent	N.A.	Investigative	[31]
Chk1-A	DMLCZ3D	Solid tumour/cancer	2A00-2F9Z	Investigative	[27]
CI-1040	DMF3DZX	Discovery agent	N.A.	Investigative	[29]
DEBROMOHYMENIALDISINE	DMDLER8	Discovery agent	N.A.	Investigative	[32]
GRANULATIMIDE	DM65SQK	Discovery agent	N.A.	Investigative	[28]
Isogranulatimide	DMI6NJ1	Discovery agent	N.A.	Investigative	[28]
KN-62	DMLZ89P	Discovery agent	N.A.	Investigative	[29]
N-(5,6-DIPHENYLFURO[2,3-D]PYRIMIDIN-4-YL)GLYCINE	DMEW3L0	Discovery agent	N.A.	Investigative	[20]
NU-6102	DMMOFKD	Discovery agent	N.A.	Investigative	[33]
PMID17935989C25	DML8ZBR	Discovery agent	N.A.	Investigative	[34]
PMID19364658C33	DMSE1C3	Discovery agent	N.A.	Investigative	[35]
PMID20855207C25	DMNEB6J	Discovery agent	N.A.	Investigative	[36]
RO-316233	DMAGLPW	Discovery agent	N.A.	Investigative	[29]
S-024	DMT36AB	Solid tumour/cancer	2A00-2F9Z	Investigative	[27]
S-070	DMANSCK	Solid tumour/cancer	2A00-2F9Z	Investigative	[27]
SB 218078	DMN1G5S	Discovery agent	N.A.	Investigative	[37]
SB218078	DM7LARD	Triple negative breast cancer	2C60-2C65	Investigative	[38]
V158411	DMXLHIO	Triple negative breast cancer	2C60-2C65	Investigative	[39]

References

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• [2] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [3] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [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] 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.
• [6] CHK1 inhibition as a strategy for targeting Fanconi Anemia (FA) DNA repair pathway deficient tumors. Mol Cancer. 2009 Apr 16;8:24.
• [7] UCN-01 inhibits p53 up-regulation and abrogates gamma-radiation-induced G(2)-M checkpoint independently of p53 by targeting both of the checkpoint kinases, Chk2 and Chk1. Cancer Res. 2002 Oct 15;62(20):5743-8.
• [8] The PI3K/Akt pathway as a target in the treatment of hematologic malignancies. Anticancer Agents Med Chem. 2009 Jun;9(5):550-9.
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• [11] Clinical pipeline report, company report or official report of AstraZeneca (2009).
• [12] Quantitative assessment of BCL-2:BIM complexes as a pharmacodynamic marker for venetoclax (ABT-199).
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• [14] National Cancer Institute Drug Dictionary (drug id 730054).
• [15] Structure-based design, discovery and development of checkpoint kinase inhibitors as potential anti-cancer therapies. Expert Opin Drug Discov. 2013 June; 8(6): 621-640.
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• [17] Cell cycle kinases as therapeutic targets for cancer. Nat Rev Drug Discov. 2009 Jul;8(7):547-66.
• [18] National Cancer Institute Drug Dictionary (drug id 701310).
• [19] Interpreting expression profiles of cancers by genome-wide survey of breadth of expression in normal tissues. Genomics 2005 Aug;86(2):127-41.
• [20] The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42.
• [21] Development of 6-substituted indolylquinolinones as potent Chek1 kinase inhibitors. Bioorg Med Chem Lett. 2006 Nov 15;16(22):5907-12.
• [22] Optimization of protein kinase CK2 inhibitors derived from 4,5,6,7-tetrabromobenzimidazole. J Med Chem. 2004 Dec 2;47(25):6239-47.
• [23] 4-arylazo-3,5-diamino-1H-pyrazole CDK inhibitors: SAR study, crystal structure in complex with CDK2, selectivity, and cellular effects. J Med Chem. 2006 Nov 2;49(22):6500-9.
• [24] Synthesis and evaluation of substituted benzoisoquinolinones as potent inhibitors of Chk1 kinase. Bioorg Med Chem Lett. 2007 Nov 15;17(22):6280-5.
• [25] 4-Phenylpyrrolo[3,4-c]carbazole-1,3(2H,6H)-dione inhibitors of the checkpoint kinase Wee1. Structure-activity relationships for chromophore modific... J Med Chem. 2006 Aug 10;49(16):4896-911.
• [26] Synthesis of selenophene derivatives as novel CHK1 inhibitors. Bioorg Med Chem Lett. 2010 Sep 1;20(17):5065-8.
• [27] 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: 1987).
• [28] Synthesis, in vitro antiproliferative activities, and Chk1 inhibitory properties of pyrrolo[3,4-a]carbazole-1,3-diones, pyrrolo[3,4-c]carbazole-1,3... Eur J Med Chem. 2008 Feb;43(2):282-92.
• [29] Specificity and mechanism of action of some commonly used protein kinase inhibitors. Biochem J. 2000 Oct 1;351(Pt 1):95-105.
• [30] Novel small molecule inhibitors of 3-phosphoinositide-dependent kinase-1. J Biol Chem. 2005 May 20;280(20):19867-74.
• [31] Discovery of 3-alkoxyamino-5-(pyridin-2-ylamino)pyrazine-2-carbonitriles as selective, orally bioavailable CHK1 inhibitors. J Med Chem. 2012 Nov 26;55(22):10229-40.
• [32] Potent inhibition of checkpoint kinase activity by a hymenialdisine-derived indoloazepine. Bioorg Med Chem Lett. 2004 Aug 16;14(16):4319-21.
• [33] Triazolo[1,5-a]pyrimidines as novel CDK2 inhibitors: protein structure-guided design and SAR. Bioorg Med Chem Lett. 2006 Mar 1;16(5):1353-7.
• [34] Macrocyclic ureas as potent and selective Chk1 inhibitors: an improved synthesis, kinome profiling, structure-activity relationships, and prelimina... Bioorg Med Chem Lett. 2007 Dec 1;17(23):6593-601.
• [35] Identification and SAR of squarate inhibitors of mitogen activated protein kinase-activated protein kinase 2 (MK-2). Bioorg Med Chem. 2009 May 1;17(9):3342-51.
• [36] Discovery of orally bioavailable imidazo[1,2-a]pyrazine-based Aurora kinase inhibitors. Bioorg Med Chem Lett. 2010 Nov 15;20(22):6739-43.
• [37] An indolocarbazole inhibitor of human checkpoint kinase (Chk1) abrogates cell cycle arrest caused by DNA damage. Cancer Res. 2000 Feb 1;60(3):566-72.
• [38] Chk1 inhibitor synergizes quinacrine mediated apoptosis in breast cancer cells by compromising the base excision repair cascade. Biochem Pharmacol. 2016 Apr 1;105:23-33.
• [39] Cell Density Affects the Detection of Chk1 Target Engagement by the Selective Inhibitor V158411. SLAS Discov. 2018 Feb;23(2):144-153.