Therapeutic Targets Database
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TTD Target ID: TTDC00005

Target Information
NameSerine/threonine-protein kinase Chk1    
Type of targetClinical trial target    
SynonymsChk1    
DiseaseSolid tumors
[ICD9: 140-199, 210-229   ICD10: C00-C75, C7A, C7B, D10-D36, D3A]
[1]
Drug(s)7-hydroxystaurosporinePhase IIRCC, melanoma and lymphoma; SCLC [2]
LY2603618Phase IIAncreatic cancer and non-small cell lung cancer
LY2603618Phase IINSCLC (see also pancreatic)
LY2603618Phase IIPancreatic Cancer
LY2606368Phase IICancer
UCN-01Phase IINon-Small Cell Lung Carcinoma[3][4][5][6][7]
7-hydroxystaurosporinePhase ILeukaemia and MDS; solid tumours; lymphoma and solid tumours[2]
AZD7762Phase ISolid tumours; Advanced Solid Malignancies[8]
Chk1 inhibitorPhase ICancer
GDC-0425Phase ILymphoma
GDC-0425Phase ISolid Tumors
GDC-0425Phase ISolid tumors or lymphoma
GDC-0575Phase ILymphoma
GDC-0575Phase ISolid tumors or lymphoma
PF-477736Phase IAdvanced solid tumours in combination with gemcitabine[2]
RG7602Phase ISolid tumors or lymphoma
RG7741Phase ISolid tumors or lymphoma
XL844Suspended in Phase IAdvanced solid tumours or lymphoma[1]
EC NumberEC 2.7.11.1
PathwayCell cycle
p53 signaling pathway
UniProt IDO14757
PDB Structure1IA8; 1NVQ; 1NVR; 1NVS; 1ZLT; 1ZYS; 2AYP; 2BR1; 2BRB; 2BRG; 2BRH; 2BRM; 2BRN; 2BRO; 2C3J; 2C3K; 2C3L; 2CGU; 2CGV; 2CGW; 2CGX; 2E9N; 2E9O; 2E9P; 2E9U; 2E9V; 2GDO; 2GHG; 2HOG; 2HXL; 2HXQ; 2HY0; 2QHM; 2QHN; 2R0U; 2WMQ; 2WMR; 2WMS; 2WMT; 2WMU; 2WMV; 2WMW; 2WMX; 2X8D; 2X8E; 2X8I; 2XEY; 2XEZ; 2XF0; 2YDI; 2YDJ; 2YDK; 2YER; 2YEX; 2YM3; 2YM4; 2YM5; 2YM6; 2YM7; 2YM8; 2YWP; 3F9N; 3JVR; 3JVS; 3NLB; 3OT3; 3OT8; 3PA3; 3PA4; 3PA5; 3TKH; 3TKI; 3U9N; 4FSM; 4FSN; 4FSQ; 4FSR; 4FST; 4FSU; 4FSW; 4FSY; 4FSZ; 4FT0; 4FT3; 4FT5; 4FT7; 4FT9; 4FTA; 4FTC; 4FTI; 4FTJ; 4FTK; 4FTL; 4FTM; 4FTN; 4FTO; 4FTQ; 4FTR; 4FTT; 4FTU; 4GH2; 4HYH; 4HYI; 4JIK.    
SequenceMAVPFVEDWDLVQTLGEGAYGEVQLAVNRVTEEAVAVKIVDMKRAVDCPENIKKEICINK MLNHENVVKFYGHRREGNIQYLFLEYCSGGELFDRIEPDIGMPEPDAQRFFHQLMAGVVY LHGIGITHRDIKPENLLLDERDNLKISDFGLATVFRYNNRERLLNKMCGTLPYVAPELLK RREFHAEPVDVWSCGIVLTAMLAGELPWDQPSDSCQEYSDWKEKKTYLNPWKKIDSAPLA LLHKILVENPSARITIPDIKKDRWYNKPLKKGAKRPRVTSGGVSESPSGFSKHIQSNLDF SPVNSASSEENVKYSSSQPEPRTGLSLWDTSPSYIDKLVQGISFSQPTCPDHMLLNSQLL GTPGSSQNPWQRLVKRMTRFFTKLDADKSYQCLKETCEKLGYQWKKSCMNQVTISTTDRR NNKLIFKVNLLEMDDKILVDFRLSKGDGLEFKRHFLKIKGKLIDIVSSQKVWLPAT
Target ValidationClick to Find Target Validation Information.    
Inhibitor2- (cyclohexylamino)benzoic acid[9]
3- (1H-BENZIMIDAZOL-2-YL)-1H-INDAZOLE[9]
3- (1H-indol-2-yl)quinolin-2[10]
4,5,6,7-tetrabromobenzotriazole[11]
4-[ (3,5-diamino-1H-pyrazol-4-yl)diazenyl]phenol[12]
6- (3-aminopropyl)benzo[h]isoquinolin-1[13]
6-MORPHOLIN-4-YL-9H-PURINE[9]
7-hydroxystaurosporine[2]
9-chlorobenzo[h]isoquinolin-1 (2H)-one[13]
9-hydroxypyrrolo[3,4-c]carbazole-1,3 (2H,6H)-dione[14]
A-432411[15]
AZD7762[8]
BIS-IMIDE A[16]
CI-1040,   PD-18435,   PD-184352[17]
DEBROMOHYMENIALDISINE[18]
GF-109203[17]
GRANULATIMIDE[16]
ISOGRANULATIMIDE[16]
KN-62[17]
LY-294002[17]
N- (5,6-DIPHENYLFURO[2,3-D]PYRIMIDIN-4-YL)GLYCINE[9]
NU-6102[19]
PD-98059[17]
PF-477736[2]
RO-316233[17]
SB-202190[17]
SB-203580[17]
U-0126[17]
UCN-01[3][4][5][6][7]
XL844[1]
Multitarget7-hydroxystaurosporine[2]
XL844[1]
Cross References 3D Structure
Related Literature
On-Line Medical Dictionary
Ref 1Pharmacological abrogation of S-phase checkpoint enhances the anti-tumor activity of gemcitabine in vivo. Cell Cycle. 2007 Jan 1;6(1):104-10. Epub 2007 Jan 7. To Reference
Ref 2Nat Rev Drug Discov. 2009 Jul;8(7):547-66.Cell cycle kinases as therapeutic targets for cancer. To Reference
Ref 3Characterization of an inhibitory dynamic pharmacophore for the ERCC1-XPA interaction using a combined molecular dynamics and virtual screening approach. J Mol Graph Model. 2009 May 3. [Epub ahead of print] To Reference
Ref 4CHK1 inhibition as a strategy for targeting Fanconi Anemia (FA) DNA repair pathway deficient tumors. Mol Cancer. 2009 Apr 16;8:24. To Reference
Ref 5UCN-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. To Reference
Ref 6The PI3K/Akt pathway as a target in the treatment of hematologic malignancies. Anticancer Agents Med Chem. 2009 Jun;9(5):550-9. To Reference
Ref 7Cyclin-dependent kinase inhibitors as potential targeted anticancer agents. Invest New Drugs. 2009 Mar 5. To Reference
Ref 8AstraZeneca. Product Development Pipeline. January 29 2009. To Reference
Ref 9Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. To Reference
Ref 10Bioorg Med Chem Lett. 2006 Nov 15;16(22):5907-12. Epub 2006 Sep 20.Development of 6-substituted indolylquinolinones as potent Chek1 kinase inhibitors. To Reference
Ref 11J Med Chem. 2004 Dec 2;47(25):6239-47.Optimization of protein kinase CK2 inhibitors derived from 4,5,6,7-tetrabromobenzimidazole. To Reference
Ref 12J Med Chem. 2006 Nov 2;49(22):6500-9.4-arylazo-3,5-diamino-1H-pyrazole CDK inhibitors: SAR study, crystal structure in complex with CDK2, selectivity, and cellular effects. To Reference
Ref 13Bioorg Med Chem Lett. 2007 Nov 15;17(22):6280-5. Epub 2007 Sep 7.Synthesis and evaluation of substituted benzoisoquinolinones as potent inhibitors of Chk1 kinase. To Reference
Ref 14J Med Chem. 2006 Aug 10;49(16):4896-911.4-Phenylpyrrolo[3,4-c]carbazole-1,3(2H,6H)-dione inhibitors of the checkpoint kinase Wee1. Structure-activity relationships for chromophore modification and phenyl ring substitution. To Reference
Ref 15Bioorg Med Chem Lett. 2010 Sep 1;20(17):5065-8. Epub 2010 Jul 13.Synthesis of selenophene derivatives as novel CHK1 inhibitors. To Reference
Ref 16Eur J Med Chem. 2008 Feb;43(2):282-92. Epub 2007 Apr 7.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-diones, and 2-aminopyridazino[3,4-a]pyrrolo[3,4-c]carbazole-1,3,4,7-tetraone. To Reference
Ref 17Biochem J. 2000 Oct 1;351(Pt 1):95-105.Specificity and mechanism of action of some commonly used protein kinase inhibitors. To Reference
Ref 18Bioorg Med Chem Lett. 2004 Aug 16;14(16):4319-21.Potent inhibition of checkpoint kinase activity by a hymenialdisine-derived indoloazepine. To Reference
Ref 19Bioorg Med Chem Lett. 2006 Mar 1;16(5):1353-7. Epub 2005 Dec 1.Triazolo[1,5-a]pyrimidines as novel CDK2 inhibitors: protein structure-guided design and SAR. To Reference



 

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