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

General Information of Drug (ID: DMPLV9G)

• Drug Name: OBP-801 Drug Info

Indication

Disease Entry	ICD 11	Status	REF
Solid tumour/cancer	2A00-2F9Z	Phase 1	[1]

• Cross-matching ID:
  PubChem CID: 11178958
  CAS Number: CAS 328548-11-4
  TTD Drug ID: DMPLV9G

Molecule-Related Drug Atlas

Drug(s) Targeting Histone deacetylase (HDAC)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Valproate	DMCFE9I	Epilepsy	8A60-8A68	Approved	[5]
Sodium phenylbutyrate	DMXLBCQ	Spinal muscular atrophy	8B61	Approved	[6]
HBI-8000	DMDWYUN	Non-small-cell lung cancer	2C25.Y	Registered	[2]
ITF2357	DMFZBNE	Duchenne dystrophy	8C70	Phase 3	[7]
Pracinostat	DMTD7AB	Acute myeloid leukaemia	2A60	Phase 3	[8]
NVP-LAQ824	DM8JWNA	Mood disorder	6A60-6E23	Phase 3	[9]
SNDX-275	DMH7W9X	Breast cancer	2C60-2C65	Phase 3	[2]
CMS-024-02	DMC4X7L	Solid tumour/cancer	2A00-2F9Z	Phase 3	[10]
Abexinostat	DM91LGU	Follicular lymphoma	2A80	Phase 3	[11]
PDX-101	DM6OC53	Plasma cell myeloma	2A83.1	Phase 2	[12]

Drug(s) Targeting Histone deacetylase 1 (HDAC1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Vorinostat	DMWMPD4	Adult acute monocytic leukemia		Approved	[13]
Romidepsin	DMT5GNL	Cutaneous T-cell lymphoma	2B01	Approved	[14]
Panobinostat	DM58WKG	Chronic graft versus host disease		Approved	[13]
HBI-8000	DMDWYUN	Non-small-cell lung cancer	2C25.Y	Registered	[12]
ITF2357	DMFZBNE	Duchenne dystrophy	8C70	Phase 3	[15]
NVP-LAQ824	DM8JWNA	Mood disorder	6A60-6E23	Phase 3	[16]
SNDX-275	DMH7W9X	Breast cancer	2C60-2C65	Phase 3	[9]
Phenylbutyrate	DMBHPDW	Urea cycle disorder	5C50.A	Phase 2	[17]
MGCD-0103	DM726HX	Non-small-cell lung cancer	2C25.Y	Phase 2	[13]
Resminostat	DMNE1FR	Hepatocellular carcinoma	2C12.02	Phase 2	[18]

Drug(s) Affected By Caspase-3 (CASP3)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Sevoflurane	DMC9O43	Anaesthesia	9A78.6	Approved	[19]
Arsenic trioxide	DM61TA4	Acute lymphoblastic leukaemia	2A85	Approved	[20]
Lovastatin	DM9OZWQ	Arteriosclerosis	BD40	Approved	[21]
Cidofovir	DMA13GD	Cytomegalovirus infection	1D82	Approved	[22]
Docetaxel	DMDI269	Advanced cancer	2A00-2F9Z	Approved	[23]
Etoposide	DMNH3PG	Acute myelogenous leukaemia	2A41	Approved	[24]
Cisplatin	DMRHGI9	Adenocarcinoma	2D40	Approved	[25]
Mannitol	DMSCDY9	Bronchiectasis	CA24	Approved	[26]
Doxorubicin	DMVP5YE	Acute myelogenous leukaemia	2A41	Approved	[27]
Aprepitant	DM053KT	Depression	6A70-6A7Z	Approved	[28]

Drug(s) Affected By BH3-interacting domain death agonist (BID)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Cannabidiol	DM0659E	Dravet syndrome	8A61.11	Approved	[29]
Nitric Oxide	DM1RBYG	Hypertension	BA00-BA04	Approved	[30]
Selenium	DM25CGV	N. A.	N. A.	Approved	[31]
Quercetin	DM3NC4M	Obesity	5B81	Approved	[32]
obeticholic acid	DM3Q1SM	Primary biliary cholangitis	DB96.1	Approved	[33]
Tretinoin	DM49DUI	Acne vulgaris	ED80	Approved	[34]
Arsenic trioxide	DM61TA4	Acute lymphoblastic leukaemia	2A85	Approved	[35]
Aspirin	DM672AH	Acute coronary syndrome	BA41	Approved	[36]
Hydroquinone	DM6AVR4	Melasma	ED60.1	Approved	[37]
Ciclosporin	DMAZJFX	Graft-versus-host disease	4B24	Approved	[38]

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

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Lovastatin	DM9OZWQ	Arteriosclerosis	BD40	Approved	[39]
Cisplatin	DMRHGI9	Adenocarcinoma	2D40	Approved	[40]
Etoposide	DMNH3PG	Acute myelogenous leukaemia	2A41	Approved	[41]
Cannabidiol	DM0659E	Dravet syndrome	8A61.11	Approved	[29]
Gefitinib	DM15F0X	Colon adenocarcinoma		Approved	[42]
Hydrogen peroxide	DM1NG5W	Infectious disease	1A00-CA43.1	Approved	[43]
Nitric Oxide	DM1RBYG	Hypertension	BA00-BA04	Approved	[30]
Selenium	DM25CGV	N. A.	N. A.	Approved	[44]
Ciprofloxacin XR	DM2NLS9	Acute gonococcal cervicitis		Approved	[45]
Methotrexate	DM2TEOL	Anterior urethra cancer		Approved	[46]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Histone deacetylase (HDAC)	TTBH0VX	NOUNIPROTAC	Inhibitor	[2]
Histone deacetylase 1 (HDAC1)	TT6R7JZ	HDAC1_HUMAN	Inhibitor	[3]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
BH3-interacting domain death agonist (BID)	OTOSHSHU	BID_HUMAN	Gene/Protein Processing	[4]
Caspase-3 (CASP3)	OTIJRBE7	CASP3_HUMAN	Gene/Protein Processing	[4]
Caspase-8 (CASP8)	OTA8TVI8	CASP8_HUMAN	Gene/Protein Processing	[4]

References

• [1] ClinicalTrials.gov (NCT02414516) A Dose-Escalation Study of OBP-801 in Patients With Advanced Solid Tumors. U.S. National Institutes of Health.
• [2] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [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: 2658).
• [4] Spiruchostatin A and B, novel histone deacetylase inhibitors, induce apoptosis through reactive oxygen species-mitochondria pathway in human lymphoma U937 cells. Chem Biol Interact. 2014 Sep 25;221:24-34. doi: 10.1016/j.cbi.2014.07.004. Epub 2014 Jul 29.
• [5] Transcription-independent heritability of induced histone modifications in the mouse preimplantation embryo. PLoS One. 2009 Jun 30;4(6):e6086.
• [6] Histone Deacetylase inhibitors: new promise in the treatment of immune and inflammatory diseases. Curr Drug Targets. 2010 Nov;11(11):1430-8.
• [7] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [8] 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: 8365).
• [9] Emerging therapies for multiple myeloma. Expert Opin Emerg Drugs. 2009 Mar;14(1):99-127.
• [10] US patent application no. 2012,0302,505, Cyclodextrin-based polymers for therapeutic delivery.
• [11] Phase 1 study of the oral histone deacetylase inhibitor abexinostat in patients with Hodgkin lymphoma, non-Hodgkin lymphoma, or chronic lymphocytic leukaemia. Invest New Drugs. 2015 Apr;33(2):423-31.
• [12] Interpreting expression profiles of cancers by genome-wide survey of breadth of expression in normal tissues. Genomics 2005 Aug;86(2):127-41.
• [13] Protein methyltransferases as a target class for drug discovery. Nat Rev Drug Discov. 2009 Sep;8(9):724-32.
• [14] Hughes B: 2009 FDA drug approvals. Nat Rev Drug Discov. 2010 Feb;9(2):89-92.
• [15] Emerging drugs for the therapy of primary and post essential thrombocythemia, post polycythemia vera myelofibrosis. Expert Opin Emerg Drugs. 2009 Sep;14(3):471-9.
• [16] NVP-LAQ824 is a potent novel histone deacetylase inhibitor with significant activity against multiple myeloma. Blood. 2003 Oct 1;102(7):2615-22.
• [17] Emerging disease-modifying therapies for the treatment of motor neuron disease/amyotropic lateral sclerosis. Expert Opin Emerg Drugs. 2007 May;12(2):229-52.
• [18] 2011 Pipeline of 4SC AG.
• [19] Different apoptosis ratios and gene expressions in two human cell lines after sevoflurane anaesthesia. Acta Anaesthesiol Scand. 2009 Oct;53(9):1192-9. doi: 10.1111/j.1399-6576.2009.02036.x. Epub 2009 Jun 30.
• [20] [Mechanisms underlying the effect of arsenic trioxide on proliferation inhibition and apoptosis induction in myeloma cell line u266]. Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2007 Oct;15(5):982-5.
• [21] Lovastatin lactone elicits human lung cancer cell apoptosis via a COX-2/PPAR-dependent pathway. Oncotarget. 2016 Mar 1;7(9):10345-62. doi: 10.18632/oncotarget.7213.
• [22] Induction of apoptosis by cidofovir in human papillomavirus (HPV)-positive cells. Oncol Res. 2000;12(9-10):397-408. doi: 10.3727/096504001108747855.
• [23] Comparison of burst of reactive oxygen species and activation of caspase-3 in apoptosis of K562 and HL-60 cells induced by docetaxel. Cancer Lett. 2004 Oct 8;214(1):103-13. doi: 10.1016/j.canlet.2004.03.047.
• [24] Induction of mitochondrial manganese superoxide dismutase confers resistance to apoptosis in acute myeloblastic leukaemia cells exposed to etoposide. Br J Haematol. 2000 Mar;108(3):574-81. doi: 10.1046/j.1365-2141.2000.01852.x.
• [25] Cisplatin-enhanced sensitivity of glioblastoma multiforme U251 cells to adenovirus-delivered TRAIL in vitro. Tumour Biol. 2010 Dec;31(6):613-22. doi: 10.1007/s13277-010-0077-x. Epub 2010 Jul 11.
• [26] Insulin-like growth factor I is the key growth factor in serum that protects neuroblastoma cells from hyperosmotic-induced apoptosis. J Cell Physiol. 2000 Jan;182(1):24-32. doi: 10.1002/(SICI)1097-4652(200001)182:1<24::AID-JCP3>3.0.CO;2-6.
• [27] mRNA expression analysis of a variety of apoptosis-related genes, including the novel gene of the BCL2-family, BCL2L12, in HL-60 leukemia cells after treatment with carboplatin and doxorubicin. Biol Chem. 2004 Nov;385(11):1099-103. doi: 10.1515/BC.2004.143.
• [28] Neurokinin-1 receptor (NK1R) inhibition sensitizes APL cells to anti-tumor effect of arsenic trioxide via restriction of NF-B axis: Shedding new light on resistance to Aprepitant. Int J Biochem Cell Biol. 2018 Oct;103:105-114. doi: 10.1016/j.biocel.2018.08.010. Epub 2018 Aug 23.
• [29] 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.
• [30] 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.
• [31] Death receptor 5 regulation during selenium-mediated apoptosis in human prostate cancer cells. Cancer Biol Ther. 2002 May-Jun;1(3):287-90. doi: 10.4161/cbt.83.
• [32] Quercetin potentiates apoptosis by inhibiting nuclear factor-kappaB signaling in H460 lung cancer cells. Biol Pharm Bull. 2013;36(6):944-51. doi: 10.1248/bpb.b12-01004.
• [33] Pharmacotoxicology of clinically-relevant concentrations of obeticholic acid in an organotypic human hepatocyte system. Toxicol In Vitro. 2017 Mar;39:93-103.
• [34] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [35] Combination of Poly I:C and arsenic trioxide triggers apoptosis synergistically via activation of TLR3 and mitochondrial pathways in hepatocellular carcinoma cells. Cell Biol Int. 2011 Aug;35(8):803-10. doi: 10.1042/CBI20100739.
• [36] Role of mitochondria in aspirin-induced apoptosis in human gastric epithelial cells. Am J Physiol Gastrointest Liver Physiol. 2005 Oct;289(4):G731-8. doi: 10.1152/ajpgi.00150.2005. Epub 2005 Jun 23.
• [37] p38 MAPK/PP2Ac/TTP pathway on the connection of TNF- and caspases activation on hydroquinone-induced apoptosis. Carcinogenesis. 2013 Apr;34(4):818-27. doi: 10.1093/carcin/bgs409. Epub 2013 Jan 3.
• [38] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [39] 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.
• [40] 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.
• [41] 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.
• [42] 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.
• [43] 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.
• [44] 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.
• [45] 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.
• [46] The contribution of methotrexate exposure and host factors on transcriptional variance in human liver. Toxicol Sci. 2007 Jun;97(2):582-94.