Details of the Drug

General Information of Drug (ID: DMFX6G8)

• Drug Name: Nelfinavir mesylate
• Synonyms: Nelfin; Nelfinavir (Mesylate); Nelfinavir Mesylate [USAN]; Nelfinavir Methanesulfonate; Nelfinavir mesilate; Nelfinavir mesylate; Nelfinavir mesylate hydrate; Nelfinavir; NELFINAVIR MESYLATE AG1343; Nelfinavir [INN:BAN]; (3S-(2(2S*,3S*),3alpha,4abeta,8abeta))-N-(1,1-Dimethylethyl)decahydro-2-(2-hydroxy-3-((3-hydroxy-2-methylbenzoyl)amino)-4-(phenylthio)butyl)-3-isoquinolinecarboxamide; 159989-64-7; 1UN; 2-[2-HYDROXY-3-(3-HYDROXY-2-METHYL-BENZOYLAMINO)-4-PHENYL SULFANYL-BUTYL]-DECAHYDRO-ISOQUINOLINE-3-CARBOXYLIC ACID TERT-BUTYLAMIDE; C32H45N3O4S; CHEBI:7496; HO3OGH5D7I; NLF; UNII-HO3OGH5D7I; 98D603VP8V; C32H45N3O4S.CH4O3S; CHEBI:7497; CHEMBL1205; DSSTox_CID_10777; DSSTox_GSID_33736; DSSTox_RID_79093; HSDB 7159; MFCD00931436; Nelfinavir methanesulfonate hydrate; UNII-98D603VP8V
• Affected Organisms: Human Immunodeficiency Virus
• ATC Code:
  J05AE04: Nelfinavir mesylate
  J05AE: Protease inhibitors
  J05A: DIRECT ACTING ANTIVIRALS
  J05: ANTIVIRALS FOR SYSTEMIC USE
  J: ANTIINFECTIVES FOR SYSTEMIC USE
• #Ro5 Violations (Lipinski): 1:
  Molecular Weight; 663.9
  Logarithm of the Partition Coefficient; Not Available
  Rotatable Bond Count; 10
  Hydrogen Bond Donor Count; 5
  Hydrogen Bond Acceptor Count; 9
• Chemical Identifiers:
  Formula: C33H49N3O7S2
  IUPAC Name: (3S,4aS,8aS)-N-tert-butyl-2-[(2R,3R)-2-hydroxy-3-[(3-hydroxy-2-methylbenzoyl)amino]-4-phenylsulfanylbutyl]-3,4,4a,5,6,7,8,8a-octahydro-1H-isoquinoline-3-carboxamide;methanesulfonic acid
  Canonical SMILES: CC1=C(C=CC=C1O)C(=O)NC(CSC2=CC=CC=C2)C(CN3CC4CCCCC4CC3C(=O)NC(C)(C)C)O.CS(=O)(=O)O
  InChI: NQHXCOAXSHGTIA-SKXNDZRYSA-N
  InChIKey: 1S/C32H45N3O4S.CH4O3S/c1-21-25(15-10-16-28(21)36)30(38)33-26(20-40-24-13-6-5-7-14-24)29(37)19-35-18-23-12-9-8-11-22(23)17-27(35)31(39)34-32(2,3)4;1-5(2,3)4/h5-7,10,13-16,22-23,26-27,29,36-37H,8-9,11-12,17-20H2,1-4H3,(H,33,38)(H,34,39);1H3,(H,2,3,4)/t22-,23+,26-,27-,29+;/m0./s1
• Cross-matching ID:
  PubChem CID: 64142
  ChEBI ID: CHEBI:7497
  CAS Number: 159989-65-8
  UNII: HO3OGH5D7I
  DrugBank ID: DB00220
  INTEDE ID: DR1138

Molecular Interaction Atlas of This Drug

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Substrate	[1]
Mephenytoin 4-hydroxylase (CYP2C19)	DEGTFWK	CP2CJ_HUMAN	Substrate	[2]
Cytochrome P450 3A5 (CYP3A5)	DEIBDNY	CP3A5_HUMAN	Substrate	[3]
Cytochrome P450 3A7 (CYP3A7)	DERD86B	CP3A7_HUMAN	Substrate	[3]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Adiponectin (ADIPOQ)	OTNX23LE	ADIPO_HUMAN	Gene/Protein Processing	[4]
Albumin (ALB)	OTVMM513	ALBU_HUMAN	Protein Interaction/Cellular Processes	[5]
ATP-binding cassette sub-family C member 2 (ABCC2)	OTJSIGV5	MRP2_HUMAN	Regulation of Drug Effects	[6]
ATP-dependent translocase ABCB1 (ABCB1)	OTEJROBO	MDR1_HUMAN	Drug Response	[6]
Bile salt export pump (ABCB11)	OTRU7THO	ABCBB_HUMAN	Gene/Protein Processing	[7]
Broad substrate specificity ATP-binding cassette transporter ABCG2 (ABCG2)	OTW8V2V1	ABCG2_HUMAN	Gene/Protein Processing	[6]
C-C motif chemokine 2 (CCL2)	OTAD2HEL	CCL2_HUMAN	Gene/Protein Processing	[4]
C-C motif chemokine 3 (CCL3)	OTW2H3ND	CCL3_HUMAN	Gene/Protein Processing	[4]
Caspase-3 (CASP3)	OTIJRBE7	CASP3_HUMAN	Gene/Protein Processing	[8]
Caspase-7 (CASP7)	OTAPJ040	CASP7_HUMAN	Gene/Protein Processing	[8]

References

• [1] Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675.
• [2] Impact of CYP2C19 polymorphism on the pharmacokinetics of nelfinavir in patients with pancreatic cancer. Br J Clin Pharmacol. 2015 Aug;80(2):267-75.
• [3] Differential inhibition of cytochrome P450 3A4, 3A5 and 3A7 by five human immunodeficiency virus (HIV) protease inhibitors in vitro. Basic Clin Pharmacol Toxicol. 2006 Jan;98(1):79-85.
• [4] Some HIV antiretrovirals increase oxidative stress and alter chemokine, cytokine or adiponectin production in human adipocytes and macrophages. Antivir Ther. 2007;12(4):489-500.
• [5] Binding of anti-HIV drugs to human serum albumin. IUBMB Life. 2004 Oct;56(10):609-14. doi: 10.1080/15216540400016286.
• [6] Influence of ABCB1, ABCC1, ABCC2, and ABCG2 haplotypes on the cellular exposure of nelfinavir in vivo. Pharmacogenet Genomics. 2005 Sep;15(9):599-608. doi: 10.1097/01.fpc.0000172241.42546.d3.
• [7] Interference with bile salt export pump function is a susceptibility factor for human liver injury in drug development. Toxicol Sci. 2010 Dec; 118(2):485-500.
• [8] The mitochondria-independent cytotoxic effect of nelfinavir on leukemia cells can be enhanced by sorafenib-mediated mcl-1 downregulation and mitochondrial membrane destabilization. Mol Cancer. 2010 Jan 27;9:19. doi: 10.1186/1476-4598-9-19.