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 8228	12.0 nM [IC50]
Insulin-degrading enzyme 2 Target ID: CHEMBL1293287 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17026490	Inhibitor 8228	100.0 µM [IC50]
Trypanosoma cruzi 11 Target ID: CHEMBL368 Sources: https://www.ncbi.nlm.nih.gov/pubmed/25464510	Inhibitor 8228	7.3 µM [IC50]
HepG2 16 Target ID: CHEMBL395 Sources: https://www.ncbi.nlm.nih.gov/pubmed/22759761	Inhibitor 8228	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 8360	VIRACEPT Approved Use VIRACEPT in combination with other antiretroviral agents is indicated for the treatment of HIV infection. Launch Date 8.5821122E11

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
Viracept and irregular heartbeat warning.	1999 Oct	11366874
Small molecule inhibitor of HIV-1 nuclear import suppresses HIV-1 replication in human lymphoid tissue ex vivo: a potential addition to current anti-HIV drug repertoire.	2000 Aug	10996396
Inhibition of HIV-1 protease by a boron-modified polypeptide.	2000 Oct 1	10974201
Anti-toxoplasma activities of antiretroviral drugs and interactions with pyrimethamine and sulfadiazine in vitro.	2000 Sep	10952623
In vitro resistance profile of the human immunodeficiency virus type 1 protease inhibitor BMS-232632.	2000 Sep	10952574
Identification of MK-944a: a second clinical candidate from the hydroxylaminepentanamide isostere series of HIV protease inhibitors.	2000 Sep 7	10978186
Saquinavir soft gelatin capsule: a comparative safety review.	2001	11347724
The emerging roles of non-nucleoside reverse transcriptase inhibitors in antiretroviral therapy.	2001	11217868
Analysis of HIV-1 mutation patterns in patients failing antiretroviral therapy.	2001	11170234
Virologic outcome and predictors of virologic failure of highly active antiretroviral therapy containing protease inhibitors.	2001 Apr	11359661
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
Differences in the intracellular accumulation of HIV protease inhibitors in vitro and the effect of active transport.	2001 Apr 13	11371681
Determination of serum levels of thirteen human immunodeficiency virus-suppressing drugs by high-performance liquid chromatography.	2001 Apr 13	11355843
Determination of interaction kinetic constants for HIV-1 protease inhibitors using optical biosensor technology.	2001 Apr 15	11401294
Antiviral drugs: current state of the art.	2001 Aug	11418355
Antiapoptotic mechanism of HIV protease inhibitors: preventing mitochondrial transmembrane potential loss.	2001 Aug 15	11493454
Antiretroviral therapy for previously treated patients.	2001 Aug 9	11496858
Nelfinavir, efavirenz, or both after the failure of nucleoside treatment of HIV infection.	2001 Aug 9	11496850
[Resistance to protease inhibitors].	2001 Feb	11428058
Sensitive and rapid method for the simultaneous quantification of the HIV-protease inhibitors indinavir, nelfinavir, ritonavir, and saquinavir in human plasma by reversed-phase liquid chromatography.	2001 Feb	11206045
Failure of postexposure prophylaxis after sexual exposure to HIV.	2001 Feb 16	11273232
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
The use of and response to second-line protease inhibitor regimens: results from the EuroSIDA study.	2001 Jan 26	11216928
The ADAM study continued: maintenance therapy after 50 weeks of induction therapy.	2001 Jan 5	11192858
Eruptive cheilitis: a new adverse effect in reactive HIV-positive patients subjected to high activity antiretroviral therapy (HAART). Presentation of six clinical cases.	2001 Jan-Feb	11488127
New developments in anti-HIV chemotherapy.	2001 Jan-Feb	11347962
CMVR diagnoses and progression of CD4 cell counts and HIV viral load measurements in HIV patients on HAART.	2001 Jul	11423459
Capillary electrophoretic separation of protease inhibitors used in human immunodeficiency virus therapy.	2001 Jul 13	11486877
AVANTI 3: a randomized, double-blind trial to compare the efficacy and safety of lamivudine plus zidovudine versus lamivudine plus zidovudine plus nelfinavir in HIV-1-infected antiretroviral-naive patients.	2001 Jun	11491417
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
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
The binding energetics of first- and second-generation HIV-1 protease inhibitors: implications for drug design.	2001 Jun 15	11396919
Predictors of virological response in HIV-infected patients to salvage antiretroviral therapy that includes nelfinavir.	2001 Mar	11417761
Phase III trials for new PI.	2001 Mar	11313031
The safety and antiviral effect of protease inhibitors in children.	2001 Mar	11253853
Lack of removal of nelfinavir during a haemodialysis session in an HIV-1 infected patient with hepatic and renal insufficiency.	2001 Mar	11239052
Feasibility of postexposure prophylaxis (PEP) against human immunodeficiency virus infection after sexual or injection drug use exposure: the San Francisco PEP Study.	2001 Mar 1	11181146
Severe bleeding complications in HIV-positive haemophiliac patients treated with protease inhibitors.	2001 Mar 26	11309224
Sequencing of protease inhibitor therapy: insights from an analysis of HIV phenotypic resistance in patients failing protease inhibitors.	2001 Mar 30	11316998
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
Low incidence of genotypic and phenotypic resistance in paediatric HIV-infected patients on long-term first-line antiretroviral triple therapy.	2001 May 25	11399999
Editorial comment on Analysis of variation in plasma concentrations of nelfinavir and its active metabolite M8 in HIV-positive patients.	2001 May 25	11399989
Sexual dysfunction associated with protease inhibitor containing highly active antiretroviral treatment.	2001 May 25	11399984
Analysis of variation in plasma concentrations of nelfinavir and its active metabolite M8 in HIV-positive patients.	2001 May 25	11399981
Novel low molecular weight spirodiketopiperazine derivatives potently inhibit R5 HIV-1 infection through their antagonistic effects on CCR5.	2001 Sep 14	11454872

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