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

General Information of Drug (ID: DMBQRA8)

• Drug Name: NVX-207 Drug Info
• Synonyms: Sterol analog (anticancer), Novelix

Indication

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

• Cross-matching ID:
  PubChem CID: 9960374
  TTD Drug ID: DMBQRA8

Molecule-Related Drug Atlas

Drug(s) Targeting Caspase-9 (CASP9)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
isatin sulfonamide 34	DM21Y8J	Cystic fibrosis	CA25	Clinical trial	[3]
Glionitrin A	DM98CSW	Solid tumour/cancer	2A00-2F9Z	Investigative	[4]
Z-LEHD-fmk	DMEFHQI	Discovery agent	N.A.	Investigative	[5]

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

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Sevoflurane	DMC9O43	Anaesthesia	9A78.6	Approved	[6]
Arsenic trioxide	DM61TA4	Acute lymphoblastic leukaemia	2A85	Approved	[7]
Lovastatin	DM9OZWQ	Arteriosclerosis	BD40	Approved	[8]
Cidofovir	DMA13GD	Cytomegalovirus infection	1D82	Approved	[9]
Docetaxel	DMDI269	Advanced cancer	2A00-2F9Z	Approved	[10]
Etoposide	DMNH3PG	Acute myelogenous leukaemia	2A41	Approved	[11]
Cisplatin	DMRHGI9	Adenocarcinoma	2D40	Approved	[12]
Mannitol	DMSCDY9	Bronchiectasis	CA24	Approved	[13]
Doxorubicin	DMVP5YE	Acute myelogenous leukaemia	2A41	Approved	[14]
Aprepitant	DM053KT	Depression	6A70-6A7Z	Approved	[15]

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

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Lovastatin	DM9OZWQ	Arteriosclerosis	BD40	Approved	[16]
Cisplatin	DMRHGI9	Adenocarcinoma	2D40	Approved	[17]
Etoposide	DMNH3PG	Acute myelogenous leukaemia	2A41	Approved	[18]
Cannabidiol	DM0659E	Dravet syndrome	8A61.11	Approved	[19]
Gefitinib	DM15F0X	Colon adenocarcinoma		Approved	[20]
Hydrogen peroxide	DM1NG5W	Infectious disease	1A00-CA43.1	Approved	[21]
Nitric Oxide	DM1RBYG	Hypertension	BA00-BA04	Approved	[22]
Selenium	DM25CGV	N. A.	N. A.	Approved	[23]
Ciprofloxacin XR	DM2NLS9	Acute gonococcal cervicitis		Approved	[24]
Methotrexate	DM2TEOL	Anterior urethra cancer		Approved	[25]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Caspase-9 (CASP9)	TTB6T7O	CASP9_HUMAN	Modulator	[1]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Caspase-3 (CASP3)	OTIJRBE7	CASP3_HUMAN	Gene/Protein Processing	[2]
Caspase-8 (CASP8)	OTA8TVI8	CASP8_HUMAN	Gene/Protein Processing	[2]

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. (Target id: 1625).
• [2] In vitro anticancer activity of Betulinic acid and derivatives thereof on equine melanoma cell lines from grey horses and in vivo safety assessment of the compound NVX-207 in two horses. Chem Biol Interact. 2016 Feb 25;246:20-9. doi: 10.1016/j.cbi.2016.01.002. Epub 2016 Jan 7.
• [3] Potent and selective nonpeptide inhibitors of caspases 3 and 7. J Med Chem. 2001 Jun 7;44(12):2015-26.
• [4] Glionitrin A, a new diketopiperazine disulfide, activates ATM-ATR-Chk1/2 via 53BP1 phosphorylation in DU145 cells and shows antitumor effect in xenograft model. Biol Pharm Bull. 2014;37(3):378-86.
• [5] The expression of Smac and XIAP in rat hippocampus following limbic seizure induced by kainic acid injection into amygdaloid nucleus. Sheng Li Xue Bao. 2004 Apr 25;56(2):172-7.
• [6] 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.
• [7] [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.
• [8] 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.
• [9] Induction of apoptosis by cidofovir in human papillomavirus (HPV)-positive cells. Oncol Res. 2000;12(9-10):397-408. doi: 10.3727/096504001108747855.
• [10] 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.
• [11] 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.
• [12] 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.
• [13] 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.
• [14] 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.
• [15] 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.
• [16] 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.
• [17] 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.
• [18] 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.
• [19] 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.
• [20] 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.
• [21] 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.
• [22] 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.
• [23] 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.
• [24] 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.
• [25] The contribution of methotrexate exposure and host factors on transcriptional variance in human liver. Toxicol Sci. 2007 Jun;97(2):582-94.