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

General Information of Drug (ID: DMS62T0)

• Drug Name: Cdk1/2 inhibitor III Drug Info
• Synonyms: Cdk1/2 Inhibitor III; 443798-55-8; CDK 1/2 INHIBITOR; UNII-LFR1253W75; LFR1253W75; 5-AMINO-3-{[4-(AMINOSULFONYL)PHENYL]AMINO}-N-(2,6-DIFLUOROPHENYL)-1H-1,2,4-TRIAZOLE-1-CARBOTHIOAMIDE; 5-amino-N-(2,6-difluorophenyl)-3-[(4-sulfamoylphenyl)amino]-1H-1,2,4-triazole-1-carbothioamide; 5-Amino-3-((4-(aminosulfonyl)phenyl)amino)-N-(2,6-difluorophenyl)-1H-1,2,4-triazole-1-carbothioamide; 2wu6; AC1NS9OB; CHEMBL261720; GTPL5946; BDBM6878; SCHEMBL1394721; CTK8E9250; DTXSID60416209; MolPort-044-561-528; HMS3229C16; ZINC12355112; DB07664

Indication

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

• Cross-matching ID:
  PubChem CID: 5330812
  CAS Number: CAS 443798-47-8
  TTD Drug ID: DMS62T0

Molecule-Related Drug Atlas

Drug(s) Targeting Cyclin-dependent kinase 1 (CDK1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
R-roscovitine	DMSH108	Non-small-cell lung cancer	2C25.Y	Phase 2	[3]
Ro 31-7453	DM83QCL	Solid tumour/cancer	2A00-2F9Z	Phase 2	[4]
P276-00	DM9DJL2	Mantle cell lymphoma	2A85.5	Phase 2	[3]
P-276	DMMJUHD	Breast cancer	2C60-2C65	Phase 2	[5]
RGB-286638	DMEGOQP	Haematological malignancy	2B33.Y	Phase 1	[6]
AG-024322	DMY4WVK	Solid tumour/cancer	2A00-2F9Z	Phase 1	[3]
PHA-793887	DM2Y4FG	Solid tumour/cancer	2A00-2F9Z	Phase 1	[7]
Oxazolyl methylthiothiazole derivative 1	DMZM6FW	N. A.	N. A.	Patented	[8]
PMID25991433-Compound-A1	DM89LF0	N. A.	N. A.	Patented	[9]
KENPAULLONE	DMAGVXW	Discovery agent	N.A.	Patented	[10]

Drug(s) Targeting Cyclin-dependent kinase 2 (CDK2)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
R-roscovitine	DMSH108	Non-small-cell lung cancer	2C25.Y	Phase 2	[3]
Ro 31-7453	DM83QCL	Solid tumour/cancer	2A00-2F9Z	Phase 2	[4]
PHA848125	DMS2Q9G	Thymic cancer	2C27	Phase 2	[11]
TG02	DMZFIGQ	Anaplastic astrocytoma	2A00.0	Phase 1/2	[12]
NUV-422	DMQJQNT	Malignant glioma	2A00.0	Phase 1/2	[13]
RGB-286638	DMEGOQP	Haematological malignancy	2B33.Y	Phase 1	[6]
FN-1501	DM7BMD6	Solid tumour/cancer	2A00-2F9Z	Phase 1	[14]
AG-024322	DMY4WVK	Solid tumour/cancer	2A00-2F9Z	Phase 1	[3]
PHA-793887	DM2Y4FG	Solid tumour/cancer	2A00-2F9Z	Phase 1	[7]
SNS-032	DMEITAS	Solid tumour/cancer	2A00-2F9Z	Phase 1	[15]

Drug(s) Targeting VEGFR1 messenger RNA (VEGFR1 mRNA)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Romiplostim	DM3U7SZ	Thrombocytopenia	3B64	Approved	[16]
VATALANIB	DMY0UEQ	Solid tumour/cancer	2A00-2F9Z	Phase 2	[17]
MK-2461	DM21WBH	Alzheimer disease	8A20	Phase 1/2	[18]
Sirna-027	DMZTQD8	Exudative age-related macular degeneration	9B78.3Z	Phase 1/2	[19]
PMID22765894C8h	DMH5RFU	Discovery agent	N.A.	Investigative	[20]
2-(1H-indazol-3-yl)-1H-benzo[d]imidazole	DM0CSH8	Discovery agent	N.A.	Investigative	[21]
AAL-993	DM35RFH	Discovery agent	N.A.	Investigative	[17]
PMID17935989C25	DML8ZBR	Discovery agent	N.A.	Investigative	[22]
2-(5-Phenyl-oxazol-2-ylamino)-benzonitrile	DMX6QMT	Discovery agent	N.A.	Investigative	[23]
4-Chloro-N-(3-chloro-benzoyl)-benzenesulfonamide	DMI3OR9	Discovery agent	N.A.	Investigative	[24]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Cyclin-dependent kinase 1 (CDK1)	TTH6V3D	CDK1_HUMAN	Inhibitor	[2]
Cyclin-dependent kinase 2 (CDK2)	TT7HF4W	CDK2_HUMAN	Inhibitor	[2]
VEGFR1 messenger RNA (VEGFR1 mRNA)	TT1VAUK	VGFR1_HUMAN	Inhibitor	[2]

References

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• [2] 1-Acyl-1H-[1,2,4]triazole-3,5-diamine analogues as novel and potent anticancer cyclin-dependent kinase inhibitors: synthesis and evaluation of biological activities. J Med Chem. 2005 Jun 30;48(13):4208-11.
• [3] Cell cycle kinases as therapeutic targets for cancer. Nat Rev Drug Discov. 2009 Jul;8(7):547-66.
• [4] 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.
• [5] P276-00, a novel cyclin-dependent inhibitor induces G1-G2 arrest, shows antitumor activity on cisplatin-resistant cells and significant in vivo efficacy in tumor models. Mol Cancer Ther. 2007 Mar;6(3):926-34.
• [6] Small-molecule multi-targeted kinase inhibitor RGB-286638 triggers P53-dependent and -independent anti-multiple myeloma activity through inhibition of transcriptional CDKs. Leukemia. 2013 Dec;27(12):2366-75.
• [7] A first in man, phase I dose-escalation study of PHA-793887, an inhibitor of multiple cyclin-dependent kinases (CDK2, 1 and 4) reveals unexpected h... Cell Cycle. 2011 Mar 15;10(6):963-70.
• [8] Cyclin-dependent kinase inhibitors for cancer therapy: a patent review (2009 - 2014).Expert Opin Ther Pat. 2015;25(9):953-70.
• [9] c-Jun N-terminal kinase inhibitors: a patent review (2010 - 2014).Expert Opin Ther Pat. 2015;25(8):849-72.
• [10] Discovery of novel CDK1 inhibitors by combining pharmacophore modeling, QSAR analysis and in silico screening followed by in vitro bioassay. Eur J Med Chem. 2010 Sep;45(9):4316-30.
• [11] Identification of N,1,4,4-tetramethyl-8-{[4-(4-methylpiperazin-1-yl)phenyl]amino}-4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline-3-carboxamide (PHA-848125), a potent, orally available cyclin dependent kinase inhibitor. J Med Chem. 2009 Aug 27;52(16):5152-63.
• [12] Preclinical metabolism and pharmacokinetics of SB1317 (TG02), a potent CDK/JAK2/FLT3 inhibitor. Drug Metab Lett. 2012 Mar;6(1):33-42.
• [13] ClinicalTrials.gov (NCT04541225) Phase 1/2 Dose Escalation, Safety, Pharmacokinetics, and Efficacy Study of NUV-422 in Adults With Recurrent or Refractory High-grade Gliomas and Solid Tumors. U.S.National Institutes of Health.
• [14] Discovery of 4-((7H-Pyrrolo[2,3-d]pyrimidin-4-yl)amino)-N-(4-((4-methylpiperazin-1-yl)methyl)phenyl)-1H-pyrazole-3-carboxamide (FN-1501), an FLT3- and CDK-Kinase Inhibitor with Potentially High Efficiency against Acute Myelocytic Leukemia. J Med Chem. 2018 Feb 22;61(4):1499-1518.
• [15] Mechanism of action of SNS-032, a novel cyclin-dependent kinase inhibitor, in chronic lymphocytic leukemia. Blood. 2009 May 7;113(19):4637-45.
• [16] New anilinophthalazines as potent and orally well absorbed inhibitors of the VEGF receptor tyrosine kinases useful as antagonists of tumor-driven a... J Med Chem. 2000 Jun 15;43(12):2310-23.
• [17] Inhibitors of VEGF receptors-1 and -2 based on the 2-((pyridin-4-yl)ethyl)pyridine template. Bioorg Med Chem Lett. 2006 Apr 1;16(7):1913-9.
• [18] MK-2461, a novel multitargeted kinase inhibitor, preferentially inhibits the activated c-Met receptor. Cancer Res. 2010 Feb 15;70(4):1524-33.
• [19] 2011 Pipeline of Sirna Therapeutics.
• [20] The design, synthesis, and biological evaluation of potent receptor tyrosine kinase inhibitors. Bioorg Med Chem Lett. 2012 Aug 1;22(15):4979-85.
• [21] Design and structure-activity relationship of 3-benzimidazol-2-yl-1H-indazoles as inhibitors of receptor tyrosine kinases. Bioorg Med Chem Lett. 2006 Jul 1;16(13):3595-9.
• [22] 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.
• [23] Discovery and evaluation of 2-anilino-5-aryloxazoles as a novel class of VEGFR2 kinase inhibitors. J Med Chem. 2005 Mar 10;48(5):1610-9.
• [24] Acyl sulfonamide anti-proliferatives: benzene substituent structure-activity relationships for a novel class of antitumor agents. J Med Chem. 2004 Oct 21;47(22):5367-80.