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

General Information of Drug (ID: DM6B9HP)

• Drug Name: Apomine Drug Info
• Synonyms: Apomine; SR-45023A; UNII-JQ95208805; JQ95208805; SR-9223i; SR 45023A; APB-231-A2; SKF 99085; F-99085; 126411-13-0; SCHEMBL1648488; AC1L423G; DB12276; 4-[2,2-bis[di(propan-2-yloxy)phosphoryl]ethyl]-2,6-ditert-butylphenol; tetraisopropyl 2-(3,5-di-tert-butyl-4-hydroxyphenyl)ethyl-1,1-biphosphonate; Phosphonic acid, (2-(3,5-bis(1,1-dimethylethyl)-4-hydroxyphenyl)ethylidene)bis-, tetrakis(1-methylethyl); SK&F-99085; 2-(3,5-Di-tert-butyl-4-hydroxyphenyl)ethylidene-1,1-diphosphonic acid tetraisopropyl ester; SR-45023A (Apomine)

Indication

Disease Entry	ICD 11	Status	REF
Osteopetrosis	LD24.10	Phase 2	[1]

• Cross-matching ID:
  PubChem CID: 176405
  CAS Number: CAS 126411-13-0
  TTD Drug ID: DM6B9HP

Molecule-Related Drug Atlas

Drug(s) Targeting Farnesoid X-activated receptor (FXR)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Chenodiol	DMQ8JIK	Cholelithiasis	DC11	Approved	[4]
Guggulsterone	DMP7LK1	Osteoarthritis	FA00-FA05	Approved	[5]
obeticholic acid	DM3Q1SM	Primary biliary cholangitis	DB96.1	Approved	[6]
GS-9674	DM936V7	Primary sclerosing cholangitis	DB96.2	Phase 3	[7]
LJN452	DM3XRUH	Primary biliary cholangitis	DB96.1	Phase 2	[8]
EYP001	DM5PBLM	Non-alcoholic steatohepatitis	DB92.1	Phase 2	[9]
EDP-305	DMGJYZ8	Non-alcoholic steatohepatitis	DB92.1	Phase 2	[10]
LMB763	DMQOXNL	Diabetic nephropathy	GB61.Z	Phase 2	[11]
MET409	DM89QXT	Non-alcoholic steatohepatitis	DB92.1	Phase 2	[12]
Turofexorate isopropyl	DM36ONA	Hyperlipidaemia	5C80	Phase 1	[13]

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

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Sevoflurane	DMC9O43	Anaesthesia	9A78.6	Approved	[14]
Arsenic trioxide	DM61TA4	Acute lymphoblastic leukaemia	2A85	Approved	[15]
Lovastatin	DM9OZWQ	Arteriosclerosis	BD40	Approved	[16]
Cidofovir	DMA13GD	Cytomegalovirus infection	1D82	Approved	[17]
Docetaxel	DMDI269	Advanced cancer	2A00-2F9Z	Approved	[18]
Etoposide	DMNH3PG	Acute myelogenous leukaemia	2A41	Approved	[19]
Cisplatin	DMRHGI9	Adenocarcinoma	2D40	Approved	[20]
Mannitol	DMSCDY9	Bronchiectasis	CA24	Approved	[21]
Doxorubicin	DMVP5YE	Acute myelogenous leukaemia	2A41	Approved	[22]
Aprepitant	DM053KT	Depression	6A70-6A7Z	Approved	[23]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Farnesoid X-activated receptor (FXR)	TTS4UGC	NR1H4_HUMAN	Agonist	[2]

Drug Off-Target (DOT)

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

References

• [1] A phase II open-label trial of apomine (SR-45023A) in patients with refractory melanoma. Invest New Drugs. 2006 Jan;24(1):89-94.
• [2] The nuclear receptors FXR and LXRalpha: potential targets for the development of drugs affecting lipid metabolism and neoplastic diseases. Curr Pharm Des. 2001 Mar;7(4):231-59.
• [3] The mevalonate/isoprenoid pathway inhibitor apomine (SR-45023A) is antiproliferative and induces apoptosis similar to farnesol. Biochem Biophys Res Commun. 2000 Apr 2;270(1):240-6. doi: 10.1006/bbrc.2000.2421.
• [4] Lithocholic acid decreases expression of bile salt export pump through farnesoid X receptor antagonist activity. J Biol Chem. 2002 Aug 30;277(35):31441-7.
• [5] Effect of guggulsterone and cembranoids of Commiphora mukul on pancreatic phospholipase A(2): role in hypocholesterolemia. J Nat Prod. 2009 Jan;72(1):24-8.
• [6] 2016 FDA drug approvals. Nat Rev Drug Discov. 2017 Feb 2;16(2):73-76.
• [7] The Nonsteroidal Farnesoid X Receptor Agonist Cilofexor (GS-9674) Improves Markers of Cholestasis and Liver Injury in Patients With Primary Sclerosing Cholangitis. Hepatology. 2019 Sep;70(3):788-801.
• [8] FXR modulators for enterohepatic and metabolic diseases.Expert Opin Ther Pat. 2018 Nov;28(11):765-782.
• [9] Clinical pipeline report, company report or official report of ENYO Pharma.
• [10] A novel non-bile acid FXR agonist EDP-305 potently suppresses liver injury and fibrosis without worsening of ductular reaction. Liver Int. 2020 Jul;40(7):1655-1669.
• [11] Nidufexor (LMB763), a Novel FXR Modulator for the Treatment of Nonalcoholic Steatohepatitis. J Med Chem. 2020 Apr 23;63(8):3868-3880.
• [12] Clinical pipeline report, company report or official report of Metacrine.
• [13] A synthetic farnesoid X receptor (FXR) agonist promotes cholesterol lowering in models of dyslipidemia. Am J Physiol Gastrointest Liver Physiol. 2009 Mar;296(3):G543-52.
• [14] 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.
• [15] [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.
• [16] 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.
• [17] Induction of apoptosis by cidofovir in human papillomavirus (HPV)-positive cells. Oncol Res. 2000;12(9-10):397-408. doi: 10.3727/096504001108747855.
• [18] 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.
• [19] 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.
• [20] 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.
• [21] 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.
• [22] 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.
• [23] 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.