Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTAMQ62)

• DTT Name: Cyclin A2 (CCNA2)
• Synonyms: Cyclin-A2; Cyclin-A; Cyclin A; CCNA
• Gene Name: CCNA2
• DTT Type: Literature-reported target; [1]
• UniProt ID: CCNA2_HUMAN
• TTD ID: T58470
• Sequence:
  MLGNSAPGPATREAGSALLALQQTALQEDQENINPEKAAPVQQPRTRAALAVLKSGNPRG
  LAQQQRPKTRRVAPLKDLPVNDEHVTVPPWKANSKQPAFTIHVDEAEKEAQKKPAESQKI
  EREDALAFNSAISLPGPRKPLVPLDYPMDGSFESPHTMDMSIILEDEKPVSVNEVPDYHE
  DIHTYLREMEVKCKPKVGYMKKQPDITNSMRAILVDWLVEVGEEYKLQNETLHLAVNYID
  RFLSSMSVLRGKLQLVGTAAMLLASKFEEIYPPEVAEFVYITDDTYTKKQVLRMEHLVLK
  VLTFDLAAPTVNQFLTQYFLHQQPANCKVESLAMFLGELSLIDADPYLKYLPSVIAGAAF
  HLALYTVTGQSWPESLIRKTGYTLESLKPCLMDLHQTYLKAPQHAQQSIREKYKNSKYHG
  VSLLNPPETLNL
• Function: Functions through the formation of specific serine/threonine protein kinase holoenzyme complexes with the cyclin-dependent protein kinases CDK1 or CDK2. The cyclin subunit confers the substrate specificity of these complexes and differentially interacts with and activates CDK1 and CDK2 throughout the cell cycle. Cyclin which controls both the G1/S and the G2/M transition phases of the cell cycle.
• KEGG Pathway:
  DNA replication (hsa03030)
  Base excision repair (hsa03410)
  Nucleotide excision repair (hsa03420)
  Mismatch repair (hsa03430)
  Cell cycle (hsa04110)
  Hepatitis B (hsa05161)
  HTLV-I infection (hsa05166)
• Reactome Pathway:
  G0 and Early G1 (R-HSA-1538133)
  Cdc20 (R-HSA-174184)
  Regulation of APC/C activators between G1/S and early anaphase (R-HSA-176408)
  SCF(Skp2)-mediated degradation of p27/p21 (R-HSA-187577)
  Senescence-Associated Secretory Phenotype (SASP) (R-HSA-2559582)
  Mismatch repair (MMR) directed by MSH2 (R-HSA-5358565)
  Mismatch repair (MMR) directed by MSH2 (R-HSA-5358606)
  HDR through Homologous Recombination (HRR) (R-HSA-5685942)
  Processing of DNA double-strand break ends (R-HSA-5693607)
  Dual Incision in GG-NER (R-HSA-5696400)
  Dual incision in TC-NER (R-HSA-6782135)
  Gap-filling DNA repair synthesis and ligation in TC-NER (R-HSA-6782210)
  G2 Phase (R-HSA-68911)
  Orc1 removal from chromatin (R-HSA-68949)
  G1/S-Specific Transcription (R-HSA-69205)
  Cyclin A/B1 associated events during G2/M transition (R-HSA-69273)
  Cyclin A (R-HSA-69656)
  E2F mediated regulation of DNA replication (R-HSA-113510)

Molecular Interaction Atlas (MIA) of This DTT

1 Discontinued Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
PD-0183812	DMWYP86	Retinoblastoma	2D02.2	Terminated	[1]

22 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
2,5-dichloro-N-p-tolylthiophene-3-sulfonamide	DMU5J8Y	Discovery agent	N.A.	Investigative	[2]
3-((3,5-diamino-1H-pyrazol-4-yl)diazenyl)phenol	DMJZK40	Discovery agent	N.A.	Investigative	[3]
4-(phenyldiazenyl)-1H-pyrazole-3,5-diamine	DM54MOP	Discovery agent	N.A.	Investigative	[3]
4-[(3,5-diamino-1H-pyrazol-4-yl)diazenyl]phenol	DMSKJ1X	Discovery agent	N.A.	Investigative	[3]
6-(3-Amino-benzyloxy)-9H-purin-2-ylamine	DMJ92W0	Discovery agent	N.A.	Investigative	[4]
6-(3-Methyl-benzyloxy)-9H-purin-2-ylamine	DMSW3KN	Discovery agent	N.A.	Investigative	[4]
6-(Cyclohex-3-enylmethoxy)-9H-purin-2-ylamine	DMAYWIN	Discovery agent	N.A.	Investigative	[4]
6-Cyclohexylmethoxy-pyrimidine-2,4,5-triamine	DM9IHYS	Discovery agent	N.A.	Investigative	[5]
6-O-Cyclohexylmethyl Guanine	DMDIW08	Discovery agent	N.A.	Investigative	[6]
aloisine A	DM5U1LN	Discovery agent	N.A.	Investigative	[7]
GW-8510	DML4UMT	Discovery agent	N.A.	Investigative	[8]
MERIOLIN 1	DMJT93H	Discovery agent	N.A.	Investigative	[9]
MERIOLIN 2	DM413XJ	Discovery agent	N.A.	Investigative	[9]
MERIOLIN 3	DMVE95S	Discovery agent	N.A.	Investigative	[9]
MERIOLIN 4	DMIJMZQ	Discovery agent	N.A.	Investigative	[9]
MERIOLIN 5	DMGVLR0	Discovery agent	N.A.	Investigative	[9]
MERIOLIN 6	DMW5AXC	Discovery agent	N.A.	Investigative	[9]
MERIOLIN 7	DM8D3NY	Discovery agent	N.A.	Investigative	[9]
MERIOLIN 8	DM0E95B	Discovery agent	N.A.	Investigative	[9]
NU-6027	DMELYAX	Discovery agent	N.A.	Investigative	[5]
Purvalanol A	DMNQ7TM	Discovery agent	N.A.	Investigative	[10]
RESCOVITINE	DM2IBND	Discovery agent	N.A.	Investigative	[11]

References

• [1] Pyrido[2,3-d]pyrimidin-7-one inhibitors of cyclin-dependent kinases. J Med Chem. 2000 Nov 30;43(24):4606-16.
• [2] Activity of substituted thiophene sulfonamides against malarial and mammalian cyclin dependent protein kinases, Bioorg. Med. Chem. Lett. 20(13):3863-3867 (2010).
• [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] Probing the ATP ribose-binding domain of cyclin-dependent kinases 1 and 2 with O(6)-substituted guanine derivatives. J Med Chem. 2002 Aug 1;45(16):3381-93.
• [5] 4-Alkoxy-2,6-diaminopyrimidine derivatives: inhibitors of cyclin dependent kinases 1 and 2. Bioorg Med Chem Lett. 2003 Jan 20;13(2):217-22.
• [6] N2-substituted O6-cyclohexylmethylguanine derivatives: potent inhibitors of cyclin-dependent kinases 1 and 2. J Med Chem. 2004 Jul 15;47(15):3710-22.
• [7] 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.
• [8] Discovery and in vitro evaluation of potent TrkA kinase inhibitors: oxindole and aza-oxindoles. Bioorg Med Chem Lett. 2004 Feb 23;14(4):953-7.
• [9] Meriolins (3-(pyrimidin-4-yl)-7-azaindoles): synthesis, kinase inhibitory activity, cellular effects, and structure of a CDK2/cyclin A/meriolin com... J Med Chem. 2008 Feb 28;51(4):737-51.
• [10] The selectivity of protein kinase inhibitors: a further update. Biochem J. 2007 Dec 15;408(3):297-315.
• [11] Design, synthesis, and biological evaluation of novel pyrimidine derivatives as CDK2 inhibitors. Eur J Med Chem. 2010 Mar;45(3):1158-66.