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

General Information of Drug (ID: DMELYAX)

• Drug Name: NU-6027 Drug Info

Indication

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

• Cross-matching ID:
  PubChem CID: 398148
  CAS Number: CAS 220036-08-8
  TTD Drug ID: DMELYAX

Molecule-Related Drug Atlas

Drug(s) Targeting Cyclin A2 (CCNA2)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
PD-0183812	DMWYP86	Retinoblastoma	2D02.2	Terminated	[3]
4-[(3,5-diamino-1H-pyrazol-4-yl)diazenyl]phenol	DMSKJ1X	Discovery agent	N.A.	Investigative	[4]
aloisine A	DM5U1LN	Discovery agent	N.A.	Investigative	[5]
3-((3,5-diamino-1H-pyrazol-4-yl)diazenyl)phenol	DMJZK40	Discovery agent	N.A.	Investigative	[4]
MERIOLIN 8	DM0E95B	Discovery agent	N.A.	Investigative	[6]
2,5-dichloro-N-p-tolylthiophene-3-sulfonamide	DMU5J8Y	Discovery agent	N.A.	Investigative	[7]
Purvalanol A	DMNQ7TM	Discovery agent	N.A.	Investigative	[8]
MERIOLIN 1	DMJT93H	Discovery agent	N.A.	Investigative	[6]
MERIOLIN 4	DMIJMZQ	Discovery agent	N.A.	Investigative	[6]
MERIOLIN 6	DMW5AXC	Discovery agent	N.A.	Investigative	[6]

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	[9]
Ro 31-7453	DM83QCL	Solid tumour/cancer	2A00-2F9Z	Phase 2	[10]
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	[14]
FN-1501	DM7BMD6	Solid tumour/cancer	2A00-2F9Z	Phase 1	[15]
AG-024322	DMY4WVK	Solid tumour/cancer	2A00-2F9Z	Phase 1	[9]
PHA-793887	DM2Y4FG	Solid tumour/cancer	2A00-2F9Z	Phase 1	[16]
SNS-032	DMEITAS	Solid tumour/cancer	2A00-2F9Z	Phase 1	[17]

Drug(s) Affected By Serine/threonine-protein kinase ATR (ATR)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Quercetin	DM3NC4M	Obesity	5B81	Approved	[18]
Acetic Acid, Glacial	DM4SJ5Y	infection in the ear canal	AA0Y	Approved	[19]
Nefazodone	DM4ZS8M	Major depressive disorder	6A70.3	Approved	[20]
Arsenic trioxide	DM61TA4	Acute lymphoblastic leukaemia	2A85	Approved	[21]
Aspirin	DM672AH	Acute coronary syndrome	BA41	Approved	[22]
Acocantherin	DM7JT24	Atrial fibrillation	BC81.3	Approved	[23]
Valproate	DMCFE9I	Epilepsy	8A60-8A68	Approved	[24]
Motexafin gadolinium	DMEJKRF	Brain cancer	2A00	Approved	[19]
Cupric Sulfate	DMP0NFQ	Fungal infection	1F29-1F2F	Approved	[25]
Decitabine	DMQL8XJ	Acute myelogenous leukaemia	2A41	Approved	[26]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Cyclin A2 (CCNA2)	TTAMQ62	CCNA2_HUMAN	Inhibitor	[1]
Cyclin-dependent kinase 2 (CDK2)	TT7HF4W	CDK2_HUMAN	Inhibitor	[1]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Serine/threonine-protein kinase ATR (ATR)	OTH0OP1J	ATR_HUMAN	Gene/Protein Processing	[2]

References

• [1] 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.
• [2] Identification and evaluation of a potent novel ATR inhibitor, NU6027, in breast and ovarian cancer cell lines. Br J Cancer. 2011 Jul 26;105(3):372-81. doi: 10.1038/bjc.2011.243. Epub 2011 Jul 5.
• [3] Pyrido[2,3-d]pyrimidin-7-one inhibitors of cyclin-dependent kinases. J Med Chem. 2000 Nov 30;43(24):4606-16.
• [4] 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.
• [5] 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.
• [6] 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.
• [7] Activity of substituted thiophene sulfonamides against malarial and mammalian cyclin dependent protein kinases, Bioorg. Med. Chem. Lett. 20(13):3863-3867 (2010).
• [8] The selectivity of protein kinase inhibitors: a further update. Biochem J. 2007 Dec 15;408(3):297-315.
• [9] Cell cycle kinases as therapeutic targets for cancer. Nat Rev Drug Discov. 2009 Jul;8(7):547-66.
• [10] 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.
• [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] 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.
• [15] 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.
• [16] 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.
• [17] Mechanism of action of SNS-032, a novel cyclin-dependent kinase inhibitor, in chronic lymphocytic leukemia. Blood. 2009 May 7;113(19):4637-45.
• [18] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [19] Motexafin gadolinium and zinc induce oxidative stress responses and apoptosis in B-cell lymphoma lines. Cancer Res. 2005 Dec 15;65(24):11676-88.
• [20] Involvement of mitochondrial dysfunction in nefazodone-induced hepatotoxicity. Food Chem Toxicol. 2016 Aug;94:148-58. doi: 10.1016/j.fct.2016.06.001. Epub 2016 Jun 8.
• [21] Targeting of EGFR increase?anti-cancer effects of arsenic trioxide: Promising treatment for glioblastoma multiform. Eur J Pharmacol. 2018 Feb 5;820:274-285. doi: 10.1016/j.ejphar.2017.12.041. Epub 2017 Dec 20.
• [22] Aspirin and alterations in DNA repair proteins in the SW480 colorectal cancer cell line. Oncol Rep. 2010 Jul;24(1):37-46. doi: 10.3892/or_00000826.
• [23] Ouabain induces apoptotic cell death in human prostate DU 145 cancer cells through DNA damage and TRAIL pathways. Environ Toxicol. 2019 Dec;34(12):1329-1339. doi: 10.1002/tox.22834. Epub 2019 Aug 21.
• [24] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [25] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [26] An ATM- and Rad3-related (ATR) signaling pathway and a phosphorylation-acetylation cascade are involved in activation of p53/p21Waf1/Cip1 in response to 5-aza-2'-deoxycytidine treatment. J Biol Chem. 2008 Feb 1;283(5):2564-74. doi: 10.1074/jbc.M702454200. Epub 2007 Oct 31.