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

General Information of Drug (ID: DMJSADP)

• Drug Name: BI 2536 Drug Info
• Synonyms: BI2536, BI 2536

Indication

Disease Entry	ICD 11	Status	REF
Acute myeloid leukaemia	2A60	Phase 2	[1]

• Therapeutic Class: Anticancer Agents
• Cross-matching ID:
  PubChem CID: 11364421
  CAS Number: CAS 755038-02-9
  TTD Drug ID: DMJSADP

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	[4]
Volasertib	DMOFH1M	Acute myeloid leukaemia	2A60	Phase 3	[5]
PCM-075	DMYFRTB	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	[2]
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]
HMN-214	DMH4ANG	Pancreatic cancer	2C10	Discontinued in Phase 1	[2]

Drug(s) Affected By Caspase-8 (CASP8)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Lovastatin	DM9OZWQ	Arteriosclerosis	BD40	Approved	[11]
Cisplatin	DMRHGI9	Adenocarcinoma	2D40	Approved	[12]
Etoposide	DMNH3PG	Acute myelogenous leukaemia	2A41	Approved	[13]
Cannabidiol	DM0659E	Dravet syndrome	8A61.11	Approved	[14]
Gefitinib	DM15F0X	Colon adenocarcinoma		Approved	[15]
Hydrogen peroxide	DM1NG5W	Infectious disease	1A00-CA43.1	Approved	[16]
Nitric Oxide	DM1RBYG	Hypertension	BA00-BA04	Approved	[17]
Selenium	DM25CGV	N. A.	N. A.	Approved	[18]
Ciprofloxacin XR	DM2NLS9	Acute gonococcal cervicitis		Approved	[19]
Methotrexate	DM2TEOL	Anterior urethra cancer		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	[2]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Caspase-8 (CASP8)	OTA8TVI8	CASP8_HUMAN	Gene/Protein Processing	[3]

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: 5666).
• [2] Polo-like kinase (PLK) inhibitors in preclinical and early clinical development in oncology. Oncologist. 2009 Jun;14(6):559-70.
• [3] BRD4 associates with p53 in DNMT3A-mutated leukemia cells and is implicated in apoptosis by the bromodomain inhibitor JQ1. Cancer Med. 2013 Dec;2(6):826-35. doi: 10.1002/cam4.146. Epub 2013 Oct 31.
• [4] 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.
• [5] 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).
• [6] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [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] Statins activate the mitochondrial pathway of apoptosis in human lymphoblasts and myeloma cells. Carcinogenesis. 2005 May;26(5):883-91. doi: 10.1093/carcin/bgi036. Epub 2005 Feb 10.
• [12] Drug-induced caspase 8 upregulation sensitises cisplatin-resistant ovarian carcinoma cells to rhTRAIL-induced apoptosis. Br J Cancer. 2011 Apr 12;104(8):1278-87. doi: 10.1038/bjc.2011.84.
• [13] Essential role of caspase-8 in p53/p73-dependent apoptosis induced by etoposide in head and neck carcinoma cells. Mol Cancer. 2011 Jul 31;10:95. doi: 10.1186/1476-4598-10-95.
• [14] Cannabidiol Modulates the Immunophenotype and Inhibits the Activation of the Inflammasome in Human Gingival Mesenchymal Stem Cells. Front Physiol. 2016 Nov 24;7:559. doi: 10.3389/fphys.2016.00559. eCollection 2016.
• [15] The anti-cancer drug gefitinib accelerates Fas-mediated apoptosis by enhancing caspase-8 activation in cancer cells. J Toxicol Sci. 2019;44(6):435-440. doi: 10.2131/jts.44.435.
• [16] Melatonin enhances hydrogen peroxide-induced apoptosis in human promyelocytic leukaemia HL-60 cells. Mol Cell Biochem. 2011 Jul;353(1-2):167-76. doi: 10.1007/s11010-011-0783-8. Epub 2011 Mar 23.
• [17] Apoptotic signaling pathways induced by nitric oxide in human lymphoblastoid cells expressing wild-type or mutant p53. Cancer Res. 2004 May 1;64(9):3022-9. doi: 10.1158/0008-5472.can-03-1880.
• [18] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [19] Ciprofloxacin induces apoptosis and inhibits proliferation of human colorectal carcinoma cells. Br J Cancer. 2002 Feb 1;86(3):443-8. doi: 10.1038/sj.bjc.6600079.
• [20] The contribution of methotrexate exposure and host factors on transcriptional variance in human liver. Toxicol Sci. 2007 Jun;97(2):582-94.