NELFINAVIR

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C32H45N3O4S
Molecular Weight	567.782
Optical Activity	UNSPECIFIED
Defined Stereocenters	5 / 5
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

[H][C@@]12CCCC[C@]1([H])CN(C[C@@H](O)[C@H](CSC3=CC=CC=C3)NC(=O)C4=C(C)C(O)=CC=C4)[C@@H](C2)C(=O)NC(C)(C)C

InChI

InChIKey=QAGYKUNXZHXKMR-HKWSIXNMSA-N

InChI=1S/C32H45N3O4S/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/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)/t22-,23+,26-,27-,29+/m0/s1

HIDE SMILES / InChI

Description
Sources: http://www.drugbank.ca/drugs/DB00220
Curator's Comment: Description was created based on several sources, including http://www.accessdata.fda.gov/drugsatfda_docs/label/2011/020778s035,020779s056,021503s017lbl.pdf

Nelfinavir is a protease inhibitor with activity against Human Immunodeficiency Virus Type 1 (HIV-1). Protease inhibitors block the part of HIV called protease. HIV-1 protease is an enzyme required for the proteolytic cleavage of the viral polyprotein precursors into the individual functional proteins found in infectious HIV-1. Nelfinavir binds to the protease active site and inhibits the activity of the enzyme. This inhibition prevents cleavage of the viral polyproteins resulting in the formation of immature non-infectious viral particles. Protease inhibitors are almost always used in combination with at least two other anti-HIV drugs. Nelfinavir inhibits the HIV viral proteinase enzyme which prevents cleavage of the gag-pol polyprotein, resulting in noninfectious, immature viral particles. Nelfinavir is used in combination with other antiviral drugs in the treatment of HIV in both adults and children. Nelfinavir is marketed under the brand name Viracept.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Human immunodeficiency virus 1 33 Target ID: CHEMBL378 Sources: https://www.ncbi.nlm.nih.gov/pubmed/21256008	Inhibitor 8297	12.0 nM [IC50]
Insulin-degrading enzyme 2 Target ID: CHEMBL1293287 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17026490	Inhibitor 8297	100.0 µM [IC50]
Trypanosoma cruzi 12 Target ID: CHEMBL368 Sources: https://www.ncbi.nlm.nih.gov/pubmed/25464510	Inhibitor 8297	7.3 µM [IC50]
HepG2 16 Target ID: CHEMBL395 Sources: https://www.ncbi.nlm.nih.gov/pubmed/22759761	Inhibitor 8297	5.1 µM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
HIV infection 21 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2011/020778s035,020779s056,021503s017lbl.pdf	Primary		Approved 8429	VIRACEPT Approved Use VIRACEPT in combination with other antiretroviral agents is indicated for the treatment of HIV infection. Launch Date 1997

C_max

Value	Dose	Analyte	Population
4.7 mg/L DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/020778s041,020779s062,021503s024lbl.pdf	1250 mg 2 times / day steady-state, oral dose: 1250 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	NELFINAVIR MESYLATE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
3 mg/L DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/020778s041,020779s062,021503s024lbl.pdf	750 mg 3 times / day multiple, oral dose: 750 mg route of administration: Oral experiment type: MULTIPLE co-administered:	NELFINAVIR MESYLATE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
4 mg/L DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/020778s041,020779s062,021503s024lbl.pdf	1250 mg 2 times / day multiple, oral dose: 1250 mg route of administration: Oral experiment type: MULTIPLE co-administered:	NELFINAVIR MESYLATE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

AUC

Value	Dose	Analyte	Population
35.3 mg × h/L DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/020778s041,020779s062,021503s024lbl.pdf	1250 mg 2 times / day steady-state, oral dose: 1250 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	NELFINAVIR MESYLATE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
43.6 mg × h/L DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/020778s041,020779s062,021503s024lbl.pdf	750 mg 3 times / day multiple, oral dose: 750 mg route of administration: Oral experiment type: MULTIPLE co-administered:	NELFINAVIR MESYLATE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
52.8 mg × h/L DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/020778s041,020779s062,021503s024lbl.pdf	1250 mg 2 times / day multiple, oral dose: 1250 mg route of administration: Oral experiment type: MULTIPLE co-administered:	NELFINAVIR MESYLATE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
1.8 h REVIEW https://pubmed.ncbi.nlm.nih.gov/10200859	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:		NELFINAVIR MESYLATE plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FED
3.4 h REVIEW https://pubmed.ncbi.nlm.nih.gov/10200859	800 mg single, oral dose: 800 mg route of administration: Oral experiment type: SINGLE co-administered:		NELFINAVIR MESYLATE plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FED

F_unbound

Value	Dose	Co-administered	Analyte	Population
2% DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/020778s041,020779s062,021503s024lbl.pdf	unknown, unknown		NELFINAVIR MESYLATE serum	Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN

Doses

Dose	Population	Adverse events
1250 mg 2 times / day steady, oral MTD Dose: 1250 mg, 2 times / day Route: oral Route: steady Dose: 1250 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/24596143	unhealthy, 52 years (range: 25-77 years) n = 15 Health Status: unhealthy Condition: Adenoid Cystic Carcinoma Age Group: 52 years (range: 25-77 years) Sex: M+F Population Size: 15 Sources: https://pubmed.ncbi.nlm.nih.gov/24596143	Disc. AE: Hyponatremia, Thrombocytopenia... AEs leading to discontinuation/dose reduction: Hyponatremia (grade 4, 1 patient) Thrombocytopenia (grade 3, 1 patient) Dizziness (grade 3, 1 patient) Elevated liver enzymes (grade 3, 2 patients) Sources: https://pubmed.ncbi.nlm.nih.gov/24596143
1250 mg 2 times / day steady, oral MTD Dose: 1250 mg, 2 times / day Route: oral Route: steady Dose: 1250 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/22425919	unhealthy, 59 years (range: 54–75 years) n = 8 Health Status: unhealthy Condition: Unresectable Stage IIIA/IIIB Non-small Cell Lung Cancer Age Group: 59 years (range: 54–75 years) Sex: M+F Population Size: 8 Sources: https://pubmed.ncbi.nlm.nih.gov/22425919	Disc. AE: Esophagitis, Nausea... Other AEs: Leukopenia, Thrombocytopenia... AEs leading to discontinuation/dose reduction: Esophagitis (grade 3, 1 patient) Nausea (grade 3, 1 patient) Fatigue (grade 3, 1 patient) Other AEs: Leukopenia (grade 3, 2 patients) Thrombocytopenia (grade 3, 2 patients) Dyspnea (grade 3, 1 patient) Sources: https://pubmed.ncbi.nlm.nih.gov/22425919
650 mg 2 times / day steady, oral Dose: 650 mg, 2 times / day Route: oral Route: steady Dose: 650 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/22425919	unhealthy, 59 years (range: 54–75 years) n = 5 Health Status: unhealthy Condition: Unresectable Stage IIIA/IIIB Non-small Cell Lung Cancer Age Group: 59 years (range: 54–75 years) Sex: M+F Population Size: 5 Sources: https://pubmed.ncbi.nlm.nih.gov/22425919	Other AEs: Thrombocytopenia... Other AEs: Thrombocytopenia (grade 4, 1 patient) Sources: https://pubmed.ncbi.nlm.nih.gov/22425919

AEs

AE	Significance	Dose	Population
Dizziness	grade 3, 1 patient Disc. AE	1250 mg 2 times / day steady, oral MTD Dose: 1250 mg, 2 times / day Route: oral Route: steady Dose: 1250 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/24596143	unhealthy, 52 years (range: 25-77 years) n = 15 Health Status: unhealthy Condition: Adenoid Cystic Carcinoma Age Group: 52 years (range: 25-77 years) Sex: M+F Population Size: 15 Sources: https://pubmed.ncbi.nlm.nih.gov/24596143
Thrombocytopenia	grade 3, 1 patient Disc. AE	1250 mg 2 times / day steady, oral MTD Dose: 1250 mg, 2 times / day Route: oral Route: steady Dose: 1250 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/24596143	unhealthy, 52 years (range: 25-77 years) n = 15 Health Status: unhealthy Condition: Adenoid Cystic Carcinoma Age Group: 52 years (range: 25-77 years) Sex: M+F Population Size: 15 Sources: https://pubmed.ncbi.nlm.nih.gov/24596143
Elevated liver enzymes	grade 3, 2 patients Disc. AE	1250 mg 2 times / day steady, oral MTD Dose: 1250 mg, 2 times / day Route: oral Route: steady Dose: 1250 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/24596143	unhealthy, 52 years (range: 25-77 years) n = 15 Health Status: unhealthy Condition: Adenoid Cystic Carcinoma Age Group: 52 years (range: 25-77 years) Sex: M+F Population Size: 15 Sources: https://pubmed.ncbi.nlm.nih.gov/24596143
Hyponatremia	grade 4, 1 patient Disc. AE	1250 mg 2 times / day steady, oral MTD Dose: 1250 mg, 2 times / day Route: oral Route: steady Dose: 1250 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/24596143	unhealthy, 52 years (range: 25-77 years) n = 15 Health Status: unhealthy Condition: Adenoid Cystic Carcinoma Age Group: 52 years (range: 25-77 years) Sex: M+F Population Size: 15 Sources: https://pubmed.ncbi.nlm.nih.gov/24596143
Dyspnea	grade 3, 1 patient	1250 mg 2 times / day steady, oral MTD Dose: 1250 mg, 2 times / day Route: oral Route: steady Dose: 1250 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/22425919	unhealthy, 59 years (range: 54–75 years) n = 8 Health Status: unhealthy Condition: Unresectable Stage IIIA/IIIB Non-small Cell Lung Cancer Age Group: 59 years (range: 54–75 years) Sex: M+F Population Size: 8 Sources: https://pubmed.ncbi.nlm.nih.gov/22425919
Esophagitis	grade 3, 1 patient Disc. AE	1250 mg 2 times / day steady, oral MTD Dose: 1250 mg, 2 times / day Route: oral Route: steady Dose: 1250 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/22425919	unhealthy, 59 years (range: 54–75 years) n = 8 Health Status: unhealthy Condition: Unresectable Stage IIIA/IIIB Non-small Cell Lung Cancer Age Group: 59 years (range: 54–75 years) Sex: M+F Population Size: 8 Sources: https://pubmed.ncbi.nlm.nih.gov/22425919
Fatigue	grade 3, 1 patient Disc. AE	1250 mg 2 times / day steady, oral MTD Dose: 1250 mg, 2 times / day Route: oral Route: steady Dose: 1250 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/22425919	unhealthy, 59 years (range: 54–75 years) n = 8 Health Status: unhealthy Condition: Unresectable Stage IIIA/IIIB Non-small Cell Lung Cancer Age Group: 59 years (range: 54–75 years) Sex: M+F Population Size: 8 Sources: https://pubmed.ncbi.nlm.nih.gov/22425919
Nausea	grade 3, 1 patient Disc. AE	1250 mg 2 times / day steady, oral MTD Dose: 1250 mg, 2 times / day Route: oral Route: steady Dose: 1250 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/22425919	unhealthy, 59 years (range: 54–75 years) n = 8 Health Status: unhealthy Condition: Unresectable Stage IIIA/IIIB Non-small Cell Lung Cancer Age Group: 59 years (range: 54–75 years) Sex: M+F Population Size: 8 Sources: https://pubmed.ncbi.nlm.nih.gov/22425919
Leukopenia	grade 3, 2 patients	1250 mg 2 times / day steady, oral MTD Dose: 1250 mg, 2 times / day Route: oral Route: steady Dose: 1250 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/22425919	unhealthy, 59 years (range: 54–75 years) n = 8 Health Status: unhealthy Condition: Unresectable Stage IIIA/IIIB Non-small Cell Lung Cancer Age Group: 59 years (range: 54–75 years) Sex: M+F Population Size: 8 Sources: https://pubmed.ncbi.nlm.nih.gov/22425919
Thrombocytopenia	grade 3, 2 patients	1250 mg 2 times / day steady, oral MTD Dose: 1250 mg, 2 times / day Route: oral Route: steady Dose: 1250 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/22425919	unhealthy, 59 years (range: 54–75 years) n = 8 Health Status: unhealthy Condition: Unresectable Stage IIIA/IIIB Non-small Cell Lung Cancer Age Group: 59 years (range: 54–75 years) Sex: M+F Population Size: 8 Sources: https://pubmed.ncbi.nlm.nih.gov/22425919
Thrombocytopenia	grade 4, 1 patient	650 mg 2 times / day steady, oral Dose: 650 mg, 2 times / day Route: oral Route: steady Dose: 650 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/22425919	unhealthy, 59 years (range: 54–75 years) n = 5 Health Status: unhealthy Condition: Unresectable Stage IIIA/IIIB Non-small Cell Lung Cancer Age Group: 59 years (range: 54–75 years) Sex: M+F Population Size: 5 Sources: https://pubmed.ncbi.nlm.nih.gov/22425919

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:7496	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:7496
ChemicalBook	CB8213806	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB8213806
MolPort	MolPort-000-883-833	https://www.molport.com/shop/molecule-link/MolPort-000-883-833
ZINC	ZINC000003833846	http://zinc15.docking.org/substances/ZINC000003833846

PubMed

Title	Date	PubMed
International Congress on Chemotherapy.	1995 Sep	11362904
Symptomatic junctional bradycardia after treatment with nelfinavir.	1999 Aug	10476763
Non-active site changes elicit broad-based cross-resistance of the HIV-1 protease to inhibitors.	1999 Aug 20	10446127
Unexplained thrombosis in HIV-infected patients receiving protease inhibitors: report of seven cases.	1999 Dec	10625032
A generalized seizure following initiation of nelfinavir in a patient with human immunodeficiency virus type 1 infection, suspected due to interaction between nelfinavir and phenytoin.	1999 Mar	10337948
Inhibition of human immunodeficiency virus type 1 replication in acutely and chronically infected cells by EM2487, a novel substance produced by a Streptomyces species.	1999 Oct	10508005
Design and fast synthesis of C-terminal duplicated potent C(2)-symmetric P1/P1'-modified HIV-1 protease inhibitors.	1999 Sep 23	10508432
Structural and kinetic analyses of the protease from an amprenavir-resistant human immunodeficiency virus type 1 mutant rendered resistant to saquinavir and resensitized to amprenavir.	2000 Aug	10906218
BMS-232632, a highly potent human immunodeficiency virus protease inhibitor that can be used in combination with other available antiretroviral agents.	2000 Aug	10898681
Inhibitory effect of human immunodeficiency virus protease inhibitors on multidrug resistance transporter P-glycoproteins.	2000 Dec	11145192
A randomized, comparative study of lamivudine plus stavudine, with indinavir or nelfinavir, in treatment-experienced HIV-infected patients.	2000 Jan 28	10708286
A mutation in human immunodeficiency virus type 1 protease, N88S, that causes in vitro hypersensitivity to amprenavir.	2000 May	10756056
Inhibition of HIV-1 protease by a boron-modified polypeptide.	2000 Oct 1	10974201
An open-label randomized trial to evaluate different therapeutic strategies of combination therapy in HIV-1 infection: design, rationale, and methods of the initio trial.	2001 Apr	11306154
Circulating metabolites of the human immunodeficiency virus protease inhibitor nelfinavir in humans: structural identification, levels in plasma, and antiviral activities.	2001 Apr	11257019
Resolution of chronic parvovirus b19-induced anemia, by use of highly active antiretroviral therapy, in a patient with acquired immunodeficiency syndrome.	2001 Apr 1	11264051
High prevalence of genotypic and phenotypic HIV-1 drug-resistant strains among patients receiving antiretroviral therapy in Abidjan, Côte d'Ivoire.	2001 Apr 15	11391173
A phase II trial of dual protease inhibitor therapy: amprenavir in combination with indinavir, nelfinavir, or saquinavir.	2001 Apr 15	11391165
Lipid abnormalities in a healthcare worker receiving HIV prophylaxis.	2001 Aug	11487394
Antiviral drugs: current state of the art.	2001 Aug	11418355
Comparison of virologic, immunologic, and clinical response to five different initial protease inhibitor-containing and nevirapine-containing regimens.	2001 Aug 1	11468423
Antiretroviral therapy for previously treated patients.	2001 Aug 9	11496858
[Resistance to protease inhibitors].	2001 Feb	11428058
Ritonavir, efavirenz, and nelfinavir inhibit CYP2B6 activity in vitro: potential drug interactions with bupropion.	2001 Feb	11159797
An argument for routine therapeutic drug monitoring of HIV-1 protease inhibitors during pregnancy.	2001 Feb 16	11273224
Patterns of resistance mutations to antiretroviral drugs in extensively treated HIV-1-infected patients with failure of highly active antiretroviral therapy.	2001 Jan 1	11176267
New developments in anti-HIV chemotherapy.	2001 Jan-Feb	11347962
Capillary electrophoretic separation of protease inhibitors used in human immunodeficiency virus therapy.	2001 Jul 13	11486877
The HIV protease inhibitor nelfinavir induces insulin resistance and increases basal lipolysis in 3T3-L1 adipocytes.	2001 Jun	11375344
Severe lactic acidosis and thiamine administration in an HIV-infected patient on HAART.	2001 Jun	11368826
The effect of nevirapine in combination with nelfinavir in heavily pretreated HIV-1-infected patients: a prospective, open-label, controlled, randomized study.	2001 Jun 1	11404533
Design and synthesis of a conformationally restricted trans peptide isostere based on the bioactive conformations of saquinavir and nelfinavir.	2001 Jun 1	11374993
Simultaneous determination of the HIV-protease inhibitors indinavir, amprenavir, ritonavir, saquinavir and nelfinavir in human plasma by reversed-phase high-performance liquid chromatography.	2001 Jun 15	11417878
Structure-activity studies of FIV and HIV protease inhibitors containing allophenylnorstatine.	2001 May	11377177
Secreted aspartic proteases of Candida albicans, Candida tropicalis, Candida parapsilosis and Candida lusitaniae. Inhibition with peptidomimetic inhibitors.	2001 May	11322888
Induction of P-glycoprotein and cytochrome P450 3A by HIV protease inhibitors.	2001 May	11302944
P1/P1' modified HIV protease inhibitors as tools in two new sensitive surface plasmon resonance biosensor screening assays.	2001 May	11297905
Tolerability of postexposure prophylaxis with zidovudine, lamivudine, and nelfinavir for human immunodeficiency virus infection.	2001 May 15	11317252
Low incidence of genotypic and phenotypic resistance in paediatric HIV-infected patients on long-term first-line antiretroviral triple therapy.	2001 May 25	11399999
Mismatched double-stranded RNA (polyI-polyC(12)U) is synergistic with multiple anti-HIV drugs and is active against drug-sensitive and drug-resistant HIV-1 in vitro.	2001 Sep	11448730

Patents

Sample Use Guides

In Vivo Use Guide

The recommended dose is 1250 mg (five 250 mg tablets or two 625 mg tablets) twice daily or 750 mg (three 250 mg tablets) three times daily. VIRACEPT should be taken with a meal. Patients unable to swallow the 250 or 625 mg tablets may dissolve the tablets in a small amount of water. Once dissolved, patients should mix the cloudy liquid well, and consume it immediately.

Route of Administration: Oral

In Vitro Use Guide

Nelfinavir inhibited intracellular proteasome activity in situ at drug concentrations <40 uM in human primary myeloma cells.

Name

Type

Language

NELFINAVIR

Official Name

English

NELFINAVIR [EMA EPAR]

Common Name

English

nelfinavir [INN]

Common Name

English

Nelfinavir [WHO-DD]

Common Name

English

NELFINAVIR [MI]

Common Name

English

NSC-747167

Code

English

NELFINAVIR [VANDF]

Common Name

English

Classification Tree Code System Code

FDA ORPHAN DRUG

554316