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

General Information of Drug (ID: DM42UK5)

• Drug Name: Ro5203280 Drug Info
• Synonyms: Ro3280; Ro 3280; PharmaGSID_48511; 4-((9-Cyclopentyl-7,7-difluoro-5-methyl-6-oxo-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b][1,4]diazepin-2-yl)amino)-3-methoxy-N-(1-methylpiperidin-4-yl)benzamide; DJNZZLZKAXGMMC-UHFFFAOYSA-N; 79C; DSSTox_RID_82762; DSSTox_CID_28485; DSSTox_GSID_48511; SCHEMBL1559146; GTPL9403; DTXSID4048511; AOB5394

Indication

Disease Entry	ICD 11	Status	REF
Nasopharyngeal carcinoma	2B6B	Investigative	[1]

• Cross-matching ID:
  PubChem CID: 25015677
  CAS Number: CAS 1062243-51-9
  TTD Drug ID: DM42UK5

Molecule-Related Drug Atlas

Drug(s) Targeting Polo-like kinase 1 (PLK1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Rigosertib	DMOSTXF	Myelodysplastic syndrome	2A37	Phase 3	[3]
Volasertib	DMOFH1M	Acute myeloid leukaemia	2A60	Phase 3	[4]
PCM-075	DMYFRTB	Acute myeloid leukaemia	2A60	Phase 2	[5]
BI 2536	DMJSADP	Acute myeloid leukaemia	2A60	Phase 2	[6]
MK-1496	DME1ZAH	Solid tumour/cancer	2A00-2F9Z	Phase 1	[7]
GSK461364	DM0P729	Non-hodgkin lymphoma	2B33.5	Phase 1	[6]
TAK-960	DMN4OGH	Solid tumour/cancer	2A00-2F9Z	Phase 1	[8]
CYC140	DMC6PKJ	Acute myeloid leukaemia	2A60	Phase 1	[9]
Dihydropyrido pyrazinone compound 3	DM3PEUN	N. A.	N. A.	Patented	[10]
Dihydropyrido pyrazinone compound 2	DMOTG2Y	N. A.	N. A.	Patented	[10]

Drug(s) Affected By Neurogenic locus notch homolog protein 1 (NOTCH1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Hydrogen peroxide	DM1NG5W	Infectious disease	1A00-CA43.1	Approved	[11]
Tretinoin	DM49DUI	Acne vulgaris	ED80	Approved	[12]
Arsenic trioxide	DM61TA4	Acute lymphoblastic leukaemia	2A85	Approved	[13]
Propranolol	DM79NTF	Angina pectoris	BA40	Approved	[14]
Testosterone	DM7HUNW	Hot flushes	GA30	Approved	[15]
Valproate	DMCFE9I	Epilepsy	8A60-8A68	Approved	[16]
Enzalutamide	DMGL19D	Prostate cancer	2C82.0	Approved	[17]
Niclosamide	DMJAGXQ	Cestodes infection	1F70-1F76	Approved	[18]
Temozolomide	DMKECZD	Adenocarcinoma	2D40	Approved	[19]
Mebendazole	DMO14SG	Ascariasis	1F62	Approved	[20]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Polo-like kinase 1 (PLK1)	TTIYVQP	PLK1_HUMAN	Inhibitor	[1]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Neurogenic locus notch homolog protein 1 (NOTCH1)	OTI1WADQ	NOTC1_HUMAN	Gene/Protein Processing	[2]

References

• [1] Polo-like kinase inhibitor Ro5203280 has potent antitumor activity in nasopharyngeal carcinoma.Mol Cancer Ther. 2013 Aug;12(8):1393-401.
• [2] PLK1 targets NOTCH1 during DNA damage and mitotic progression. J Biol Chem. 2019 Nov 22;294(47):17941-17950. doi: 10.1074/jbc.RA119.009881. Epub 2019 Oct 9.
• [3] Phase I study of oral rigosertib (ON 01910.Na), a dual inhibitor of the PI3K and Plk1 pathways, in adult patients with advanced solid malignancies. Clin Cancer Res. 2014 Mar 15;20(6):1656-65.
• [4] 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: 2168).
• [5] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [6] Polo-like kinase (PLK) inhibitors in preclinical and early clinical development in oncology. Oncologist. 2009 Jun;14(6):559-70.
• [7] J Clin Oncol 29: 2011 (suppl; abstr 3012).
• [8] TAK-960, a novel, orally available, selective inhibitor of polo-like kinase 1, shows broad-spectrum preclinical antitumor activity in multiple dosing regimens. Mol Cancer Ther. 2012 Mar;11(3):700-9.
• [9] Clinical pipeline report, company report or official report of Cyclacel Pharmaceuticals.
• [10] BET inhibitors in cancer therapeutics: a patent review.Expert Opin Ther Pat. 2016;26(4):505-22.
• [11] Quercetin attenuates cell apoptosis of oxidant-stressed SK-N-MC cells while suppressing up-regulation of the defensive element, HIF-1alpha. Neuroscience. 2014 Sep 26;277:780-93.
• [12] Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
• [13] Arsenic trioxide inhibits cell growth and induces apoptosis through inactivation of notch signaling pathway in breast cancer. Int J Mol Sci. 2012;13(8):9627-9641. doi: 10.3390/ijms13089627. Epub 2012 Aug 2.
• [14] Propranolol inhibits proliferation and invasion of hemangioma-derived endothelial cells by suppressing the DLL4/Notch1/Akt pathway. Chem Biol Interact. 2018 Oct 1;294:28-33. doi: 10.1016/j.cbi.2018.08.018. Epub 2018 Aug 18.
• [15] The exosome-like vesicles derived from androgen exposed-prostate stromal cells promote epithelial cells proliferation and epithelial-mesenchymal transition. Toxicol Appl Pharmacol. 2021 Jan 15;411:115384. doi: 10.1016/j.taap.2020.115384. Epub 2020 Dec 25.
• [16] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [17] NOTCH signaling is activated in and contributes to resistance in enzalutamide-resistant prostate cancer cells. J Biol Chem. 2019 May 24;294(21):8543-8554. doi: 10.1074/jbc.RA118.006983. Epub 2019 Apr 2.
• [18] The autonomous notch signal pathway is activated by baicalin and baicalein but is suppressed by niclosamide in K562 cells. J Cell Biochem. 2009 Mar 1;106(4):682-92. doi: 10.1002/jcb.22065.
• [19] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [20] Mebendazole is a potent inhibitor to chemoresistant T cell acute lymphoblastic leukemia cells. Toxicol Appl Pharmacol. 2020 Jun 1;396:115001. doi: 10.1016/j.taap.2020.115001. Epub 2020 Apr 8.