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

General Information of Drug (ID: DMSEK5W)

• Drug Name: CVT-313 Drug Info
• Synonyms: AC1OCFD4; NG 26

Indication

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

• Cross-matching ID:
  PubChem CID: 6918386
  CAS Number: CAS 199986-75-9
  TTD Drug ID: DMSEK5W

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	[5]
Ro 31-7453	DM83QCL	Solid tumour/cancer	2A00-2F9Z	Phase 2	[6]
P276-00	DM9DJL2	Mantle cell lymphoma	2A85.5	Phase 2	[5]
P-276	DMMJUHD	Breast cancer	2C60-2C65	Phase 2	[7]
RGB-286638	DMEGOQP	Haematological malignancy	2B33.Y	Phase 1	[8]
AG-024322	DMY4WVK	Solid tumour/cancer	2A00-2F9Z	Phase 1	[5]
PHA-793887	DM2Y4FG	Solid tumour/cancer	2A00-2F9Z	Phase 1	[9]
Oxazolyl methylthiothiazole derivative 1	DMZM6FW	N. A.	N. A.	Patented	[10]
PMID25991433-Compound-A1	DM89LF0	N. A.	N. A.	Patented	[11]
KENPAULLONE	DMAGVXW	Discovery agent	N.A.	Patented	[12]

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	[5]
Ro 31-7453	DM83QCL	Solid tumour/cancer	2A00-2F9Z	Phase 2	[6]
PHA848125	DMS2Q9G	Thymic cancer	2C27	Phase 2	[13]
TG02	DMZFIGQ	Anaplastic astrocytoma	2A00.0	Phase 1/2	[14]
NUV-422	DMQJQNT	Malignant glioma	2A00.0	Phase 1/2	[15]
RGB-286638	DMEGOQP	Haematological malignancy	2B33.Y	Phase 1	[8]
FN-1501	DM7BMD6	Solid tumour/cancer	2A00-2F9Z	Phase 1	[16]
AG-024322	DMY4WVK	Solid tumour/cancer	2A00-2F9Z	Phase 1	[5]
PHA-793887	DM2Y4FG	Solid tumour/cancer	2A00-2F9Z	Phase 1	[9]
SNS-032	DMEITAS	Solid tumour/cancer	2A00-2F9Z	Phase 1	[17]

Drug(s) Affected By Retinoblastoma-associated protein (RB1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Indomethacin	DMSC4A7	Bursitis		Approved	[18]
Fulvestrant	DM0YZC6	Breast cancer	2C60-2C65	Approved	[19]
Gefitinib	DM15F0X	Colon adenocarcinoma		Approved	[20]
Talazoparib	DM1KS78	Breast cancer	2C60-2C65	Approved	[21]
Hydrogen peroxide	DM1NG5W	Infectious disease	1A00-CA43.1	Approved	[22]
Trametinib	DM2JGQ3	Melanoma	2C30	Approved	[23]
Sulindac	DM2QHZU	Acute myelogenous leukaemia	2A41	Approved	[24]
Methotrexate	DM2TEOL	Anterior urethra cancer		Approved	[25]
Simvastatin	DM30SGU	Arteriosclerosis	BD40	Approved	[26]
Quercetin	DM3NC4M	Obesity	5B81	Approved	[27]

Drug(s) Affected By Elastin (ELN)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Penicillamine	DM40EF6	Cystinuria	5C60.2	Approved	[28]
Etretinate	DM2CZFA	Keratosis	ED56	Approved	[29]
Tretinoin	DM49DUI	Acne vulgaris	ED80	Approved	[30]
Calcitriol	DM8ZVJ7	Congenital alopecia	LC30	Approved	[31]
Palbociclib	DMD7L94	Breast cancer	2C60-2C65	Approved	[4]
Dasatinib	DMJV2EK	Blast phase chronic myelogenous leukemia, BCR-ABL1 positive		Approved	[32]
Fluorouracil	DMUM7HZ	Adenocarcinoma	2D40	Approved	[33]
Doxorubicin	DMVP5YE	Acute myelogenous leukaemia	2A41	Approved	[34]
Triclosan	DMZUR4N	Malaria	1F40-1F45	Approved	[35]
Ifosfamide	DMCT3I8	Adult central nervous system germ cell tumor		Approved	[36]

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	[3]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Elastin (ELN)	OTFSO7PG	ELN_HUMAN	Gene/Protein Processing	[4]
Retinoblastoma-associated protein (RB1)	OTQJUJMZ	RB_HUMAN	Post-Translational Modifications	[4]

References

• [1] URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 5948).
• [2] A systematic interaction map of validated kinase inhibitors with Ser/Thr kinases. Proc Natl Acad Sci U S A. 2007 Dec 18;104(51):20523-8.
• [3] URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 1973).
• [4] Retinoblastoma protein modulates the inverse relationship between cellular proliferation and elastogenesis. J Biol Chem. 2011 Oct 21;286(42):36580-91. doi: 10.1074/jbc.M111.269944. Epub 2011 Aug 31.
• [5] Cell cycle kinases as therapeutic targets for cancer. Nat Rev Drug Discov. 2009 Jul;8(7):547-66.
• [6] 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.
• [7] 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.
• [8] 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.
• [9] 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.
• [10] Cyclin-dependent kinase inhibitors for cancer therapy: a patent review (2009 - 2014).Expert Opin Ther Pat. 2015;25(9):953-70.
• [11] c-Jun N-terminal kinase inhibitors: a patent review (2010 - 2014).Expert Opin Ther Pat. 2015;25(8):849-72.
• [12] 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.
• [13] 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.
• [14] Preclinical metabolism and pharmacokinetics of SB1317 (TG02), a potent CDK/JAK2/FLT3 inhibitor. Drug Metab Lett. 2012 Mar;6(1):33-42.
• [15] 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.
• [16] 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.
• [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] Indomethacin inhibits cell growth of medullary thyroid carcinoma by reducing cell cycle progression into S phase. Exp Biol Med (Maywood). 2008 Nov;233(11):1433-40. doi: 10.3181/0804-RM-127. Epub 2008 Sep 12.
• [19] Therapeutically activating RB: reestablishing cell cycle control in endocrine therapy-resistant breast cancer. Endocr Relat Cancer. 2011 Apr 28;18(3):333-45. doi: 10.1530/ERC-10-0262. Print 2011 Jun.
• [20] Effects and mechanisms of betulinic acid on improving EGFR TKI-resistance of lung cancer cells. Environ Toxicol. 2018 Nov;33(11):1153-1159.
• [21] BMN 673 (talazoparib): A potent PARP inhibitor for triple negative breast cancer with different genetic profile. J Biochem Mol Toxicol. 2019 May;33(5):e22286. doi: 10.1002/jbt.22286. Epub 2019 Jan 23.
• [22] Microarray analysis of H2O2-, HNE-, or tBH-treated ARPE-19 cells. Free Radic Biol Med. 2002 Nov 15;33(10):1419-32.
• [23] Combination small molecule MEK and PI3K inhibition enhances uveal melanoma cell death in a mutant GNAQ- and GNA11-dependent manner. Clin Cancer Res. 2012 Aug 15;18(16):4345-55. doi: 10.1158/1078-0432.CCR-11-3227. Epub 2012 Jun 25.
• [24] Sulindac induces specific degradation of the HPV oncoprotein E7 and causes growth arrest and apoptosis in cervical carcinoma cells. Cancer Lett. 2007 Jan 8;245(1-2):103-11. doi: 10.1016/j.canlet.2005.12.034. Epub 2006 Feb 20.
• [25] Melanoma coordinates general and cell-specific mechanisms to promote methotrexate resistance. Exp Cell Res. 2012 Jun 10;318(10):1146-59.
• [26] HMG-CoA reductase inhibitor simvastatin inhibits cell cycle progression at the G1/S checkpoint in immortalized lymphocytes from Alzheimer's disease patients independently of cholesterol-lowering effects. J Pharmacol Exp Ther. 2008 Jan;324(1):352-9. doi: 10.1124/jpet.107.128959. Epub 2007 Oct 10.
• [27] Inhibition of prostate cancer cell colony formation by the flavonoid quercetin correlates with modulation of specific regulatory genes. Clin Diagn Lab Immunol. 2004 Jan;11(1):63-9. doi: 10.1128/cdli.11.1.63-69.2004.
• [28] Collagen and elastin changes in D-penicillamine-induced pseudoxanthoma elasticum-like skin. Br J Dermatol. 1986 Mar;114(3):381-8. doi: 10.1111/j.1365-2133.1986.tb02832.x.
• [29] The effects of a novel synthetic retinoid, seletinoid G, on the expression of extracellular matrix proteins in aged human skin in vivo. Clin Chim Acta. 2005 Dec;362(1-2):161-9. doi: 10.1016/j.cccn.2005.06.016. Epub 2005 Aug 1.
• [30] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [31] Identification of vitamin D3 target genes in human breast cancer tissue. J Steroid Biochem Mol Biol. 2016 Nov;164:90-97.
• [32] Dasatinib reverses cancer-associated fibroblasts (CAFs) from primary lung carcinomas to a phenotype comparable to that of normal fibroblasts. Mol Cancer. 2010 Jun 27;9:168.
• [33] Cell-type-specific responses to chemotherapeutics in breast cancer. Cancer Res. 2004 Jun 15;64(12):4218-26.
• [34] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [35] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [36] ADReCS-Target: target profiles for aiding drug safety research and application. Nucleic Acids Res. 2018 Jan 4;46(D1):D911-D917. doi: 10.1093/nar/gkx899.