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

General Information of Drug (ID: DM0S82C)

• Drug Name: (2'Z,3'E)-5-Nitro-5'-hydroxy-indirubin-3'-oxime Drug Info

Indication

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

• Cross-matching ID:
  PubChem CID: 46222244
  TTD Drug ID: DM0S82C

Molecule-Related Drug Atlas

Drug(s) Targeting G1/S-specific cyclin-E1 (CCNE1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
PD-0183812	DMWYP86	Retinoblastoma	2D02.2	Terminated	[2]
4-[(3,5-diamino-1H-pyrazol-4-yl)diazenyl]phenol	DMSKJ1X	Discovery agent	N.A.	Investigative	[3]
3,4-di-(4-methoxyphenyl)-1H-pyrrole-2,5-dione	DMDO175	Discovery agent	N.A.	Investigative	[4]
3,4-diphenyl-1H-pyrrole-2,5-dione	DMPK6YT	Discovery agent	N.A.	Investigative	[4]
3-(4-methoxyphenyl)-4-phenyl-1H-pyrrole-2,5-dione	DMGC7RY	Discovery agent	N.A.	Investigative	[4]
BMS-536924	DMXJB4N	Discovery agent	N.A.	Investigative	[5]
3-(indole-3-yl)-4-phenyl-1H-pyrrole-2,5-dione	DM3EV9N	Discovery agent	N.A.	Investigative	[4]
aloisine A	DM5U1LN	Discovery agent	N.A.	Investigative	[6]
3-((3,5-diamino-1H-pyrazol-4-yl)diazenyl)phenol	DMJZK40	Discovery agent	N.A.	Investigative	[3]
(2'Z,3'E)-5-Chloro-5'-chloro-indirubin-3'-oxime	DMGXRSZ	Discovery agent	N.A.	Investigative	[1]

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	[7]
Ro 31-7453	DM83QCL	Solid tumour/cancer	2A00-2F9Z	Phase 2	[8]
PHA848125	DMS2Q9G	Thymic cancer	2C27	Phase 2	[9]
TG02	DMZFIGQ	Anaplastic astrocytoma	2A00.0	Phase 1/2	[10]
NUV-422	DMQJQNT	Malignant glioma	2A00.0	Phase 1/2	[11]
RGB-286638	DMEGOQP	Haematological malignancy	2B33.Y	Phase 1	[12]
FN-1501	DM7BMD6	Solid tumour/cancer	2A00-2F9Z	Phase 1	[13]
AG-024322	DMY4WVK	Solid tumour/cancer	2A00-2F9Z	Phase 1	[7]
PHA-793887	DM2Y4FG	Solid tumour/cancer	2A00-2F9Z	Phase 1	[14]
SNS-032	DMEITAS	Solid tumour/cancer	2A00-2F9Z	Phase 1	[15]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Cyclin-dependent kinase 2 (CDK2)	TT7HF4W	CDK2_HUMAN	Inhibitor	[1]
G1/S-specific cyclin-E1 (CCNE1)	TTCEJ4F	CCNE1_HUMAN	Inhibitor	[1]

References

• [1] 5,5'-substituted indirubin-3'-oxime derivatives as potent cyclin-dependent kinase inhibitors with anticancer activity. J Med Chem. 2010 May 13;53(9):3696-706.
• [2] Pyrido[2,3-d]pyrimidin-7-one inhibitors of cyclin-dependent kinases. J Med Chem. 2000 Nov 30;43(24):4606-16.
• [3] 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.
• [4] Design, synthesis, and biological evaluation of 3,4-diarylmaleimides as angiogenesis inhibitors. J Med Chem. 2006 Feb 23;49(4):1271-81.
• [5] Discovery of a (1H-benzoimidazol-2-yl)-1H-pyridin-2-one (BMS-536924) inhibitor of insulin-like growth factor I receptor kinase with in vivo antitum... J Med Chem. 2005 Sep 8;48(18):5639-43.
• [6] Aloisines, a new family of CDK/GSK-3 inhibitors. SAR study, crystal structure in complex with CDK2, enzyme selectivity, and cellular effects. J Med Chem. 2003 Jan 16;46(2):222-36.
• [7] Cell cycle kinases as therapeutic targets for cancer. Nat Rev Drug Discov. 2009 Jul;8(7):547-66.
• [8] 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.
• [9] 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.
• [10] Preclinical metabolism and pharmacokinetics of SB1317 (TG02), a potent CDK/JAK2/FLT3 inhibitor. Drug Metab Lett. 2012 Mar;6(1):33-42.
• [11] 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.
• [12] 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.
• [13] 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.
• [14] 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.
• [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.