Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTSMTDI)

• DTT Name: CDC7-related kinase (CDC7)
• Synonyms: huCdc7; HsCdc7; Cell division cycle 7related protein kinase; Cell division cycle 7-related protein kinase; CDC7related kinase; CDC7L1
• Gene Name: CDC7
• DTT Type: Clinical trial target; [1]
• Related Disease:
  Malignant haematopoietic neoplasm [ICD-11: 2B33]
  Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• BioChemical Class: Kinase
• UniProt ID: CDC7_HUMAN
• TTD ID: T81358
• EC Number: EC 2.7.11.1
• Sequence:
  MEASLGIQMDEPMAFSPQRDRFQAEGSLKKNEQNFKLAGVKKDIEKLYEAVPQLSNVFKI
  EDKIGEGTFSSVYLATAQLQVGPEEKIALKHLIPTSHPIRIAAELQCLTVAGGQDNVMGV
  KYCFRKNDHVVIAMPYLEHESFLDILNSLSFQEVREYMLNLFKALKRIHQFGIVHRDVKP
  SNFLYNRRLKKYALVDFGLAQGTHDTKIELLKFVQSEAQQERCSQNKSHIITGNKIPLSG
  PVPKELDQQSTTKASVKRPYTNAQIQIKQGKDGKEGSVGLSVQRSVFGERNFNIHSSISH
  ESPAVKLMKQSKTVDVLSRKLATKKKAISTKVMNSAVMRKTASSCPASLTCDCYATDKVC
  SICLSRRQQVAPRAGTPGFRAPEVLTKCPNQTTAIDMWSAGVIFLSLLSGRYPFYKASDD
  LTALAQIMTIRGSRETIQAAKTFGKSILCSKEVPAQDLRKLCERLRGMDSSTPKLTSDIQ
  GHASHQPAISEKTDHKASCLVQTPPGQYSGNSFKKGDSNSCEHCFDEYNTNLEGWNEVPD
  EAYDLLDKLLDLNPASRITAEEALLHPFFKDMSL
• Function: Can phosphorylates MCM2 and MCM3. Seems to phosphorylate critical substrates that regulate the G1/S phase transition and/or DNA replication.
• Reactome Pathway:
  Activation of the pre-replicative complex (R-HSA-68962)
  Transcriptional Regulation by E2F6 (R-HSA-8953750)
  Activation of ATR in response to replication stress (R-HSA-176187)

Molecular Interaction Atlas (MIA) of This DTT

2 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
BMS-863233	DM5HUY8	Haematological malignancy	2B33.Y	Phase 1/2	[1], [2]
TAK-931	DM1ALY9	Solid tumour/cancer	2A00-2F9Z	Phase 1	[3]

1 Patented Agent(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
PMID26161698-Compound-44	DM8UPO3	N. A.	N. A.	Patented	[4]

5 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
PHA-767491	DM4H7D5	Discovery agent	N.A.	Investigative	[5]
PMID19115845C89S	DMB9F2L	Discovery agent	N.A.	Investigative	[6]
PMID20873740C18	DMVHR3Z	Discovery agent	N.A.	Investigative	[7]
PMID24793884C74	DMFSJQC	Discovery agent	N.A.	Investigative	[8]
PMID24793884C77	DMZENGX	Discovery agent	N.A.	Investigative	[8]

References

• [1] Discovery of XL413, a potent and selective CDC7 inhibitor. Bioorg Med Chem Lett. 2012 Jun 1;22(11):3727-31.
• [2] The potent Cdc7-Dbf4 (DDK) kinase inhibitor XL413 has limited activity in many cancer cell lines and discovery of potential new DDK inhibitor scaffolds.PLoS One.2014 Nov 20;9(11):e113300.
• [3] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [4] Cyclin-dependent kinase inhibitors for cancer therapy: a patent review (2009 - 2014).Expert Opin Ther Pat. 2015;25(9):953-70.
• [5] Drug design with Cdc7 kinase: a potential novel cancer therapy target. Drug Des Devel Ther. 2009 Feb 6;2:255-64.
• [6] First Cdc7 kinase inhibitors: pyrrolopyridinones as potent and orally active antitumor agents. 2. Lead discovery. J Med Chem. 2009 Jan 22;52(2):293-307.
• [7] Cdc7 kinase inhibitors: 5-heteroaryl-3-carboxamido-2-aryl pyrroles as potential antitumor agents. 1. Lead finding. J Med Chem. 2010 Oct 28;53(20):7296-315.
• [8] Synthesis and structure-activity relationship of trisubstituted thiazoles as Cdc7 kinase inhibitors. Eur J Med Chem. 2014 Jun 10;80:364-82.