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

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

Molecular Formula	C32H45N3O4S
Molecular Weight	567.782
Charge	0
Count	MOL RATIO 1 MOL RATIO (average)

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	5 / 5
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description

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	Inhibitor	12.0 nM [IC50]
Insulin-degrading enzyme	Inhibitor	100.0 µM [IC50]
Trypanosoma cruzi	Inhibitor	7.3 µM [IC50]
HepG2	Inhibitor	5.1 µM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
HIV infection	Primary		Approved	VIRACEPT

C_max

Value	Dose	Analyte	Population
4 mg/L	1250 mg 2 times / day multiple, oral	NELFINAVIR MESYLATE plasma	Homo sapiens
3 mg/L	750 mg 3 times / day multiple, oral	NELFINAVIR MESYLATE plasma	Homo sapiens
4.7 mg/L	1250 mg 2 times / day steady-state, oral	NELFINAVIR MESYLATE plasma	Homo sapiens

AUC

Value	Dose	Analyte	Population
52.8 mg × h/L	1250 mg 2 times / day multiple, oral	NELFINAVIR MESYLATE plasma	Homo sapiens
43.6 mg × h/L	750 mg 3 times / day multiple, oral	NELFINAVIR MESYLATE plasma	Homo sapiens
35.3 mg × h/L	1250 mg 2 times / day steady-state, oral	NELFINAVIR MESYLATE plasma	Homo sapiens

T_1/2

Value	Dose	Co-administered	Analyte	Population
1.8 h	100 mg single, oral		NELFINAVIR MESYLATE plasma	Homo sapiens
3.4 h	800 mg single, oral		NELFINAVIR MESYLATE plasma	Homo sapiens

F_unbound

Value	Dose	Co-administered	Analyte	Population
2%	unknown, unknown		NELFINAVIR MESYLATE serum	Homo sapiens

Doses

Show entries

Dose	Population	Adverse events
1250 mg 2 times / day steady, oral MTD	unhealthy, 52 years (range: 25-77 years)	Disc. AE: Hyponatremia, Thrombocytopenia...
1250 mg 2 times / day steady, oral MTD	unhealthy, 59 years (range: 54–75 years)	Disc. AE: Esophagitis, Nausea... Other AEs: Leukopenia, Thrombocytopenia...
650 mg 2 times / day steady, oral	unhealthy, 59 years (range: 54–75 years)	Other AEs: Thrombocytopenia...

Showing 1 to 3 of 3 entries

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AEs

Show entries

AE	Significance	Dose	Population
Dizziness	grade 3, 1 patient Disc. AE	1250 mg 2 times / day steady, oral MTD	unhealthy, 52 years (range: 25-77 years)
Thrombocytopenia	grade 3, 1 patient Disc. AE	1250 mg 2 times / day steady, oral MTD	unhealthy, 52 years (range: 25-77 years)
Elevated liver enzymes	grade 3, 2 patients Disc. AE	1250 mg 2 times / day steady, oral MTD	unhealthy, 52 years (range: 25-77 years)
Hyponatremia	grade 4, 1 patient Disc. AE	1250 mg 2 times / day steady, oral MTD	unhealthy, 52 years (range: 25-77 years)
Dyspnea	grade 3, 1 patient	1250 mg 2 times / day steady, oral MTD	unhealthy, 59 years (range: 54–75 years)

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Sourcing

Sourcing

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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

Showing 1 to 4 of 4 entries

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PubMed

Show entries

Title	Date	PubMed
Non-active site changes elicit broad-based cross-resistance of the HIV-1 protease to inhibitors.	1999 Aug 20	10446127
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
Design and fast synthesis of C-terminal duplicated potent C(2)-symmetric P1/P1'-modified HIV-1 protease inhibitors.	1999 Sep 23	10508432
Inhibitory effect of human immunodeficiency virus protease inhibitors on multidrug resistance transporter P-glycoproteins.	2000 Dec	11145192
In vitro activity of human immunodeficiency virus protease inhibitors against Pneumocystis carinii.	2000 May	10823762

Showing 1 to 5 of 34 entries

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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.