Nelfinavir is a potent HIV-1 protease inhibitor. It is used in combination with other antiviral drugs in the treatment of HIV in both adults and children. Nelfinavir inhibits the HIV viral proteinase enzyme which prevents cleavage of the gag-pol polyprotein, resulting in noninfectious, immature viral particles.

Structure

Similar Structures

Synonyms

Nelfinavir

External IDs

AG1343

Product Ingredients

Ingredient	UNII	CAS	InChI Key
Nelfinavir mesylate	98D603VP8V	159989-65-8	NQHXCOAXSHGTIA-SKXNDZRYSA-N

Product Images

Prescription Products

Name	Dosage	Strength	Route	Labeller	Marketing Start	Marketing End
Viracept	Tablet, film coated	625 mg/1	Oral	Agouron Pharmaceuticals	2003-04-30	Not applicable
Viracept	Tablet, film coated	250 mg/1	Oral	Agouron Pharmaceuticals	1997-03-14	Not applicable
Viracept	Tablet, film coated	250 mg/1	Oral	Physicians Total Care, Inc.	1997-03-14	2002-06-30
Viracept	Tablet	625 mg	Oral	Pfizer	2004-08-11	Not applicable
Viracept	Tablet, film coated	625 mg/1	Oral	Remedy Repack	2013-03-27	2014-03-27
Viracept	Tablet, film coated	250 mg/1	Oral	PD-Rx Pharmaceuticals, Inc.	1997-03-14	Not applicable
Viracept	Tablet, film coated	250 mg/1	Oral	H.J. Harkins Company	1997-03-14	Not applicable
Viracept	Powder	50 mg/1g	Oral	AGOURON PHARMACEUTICALS, INC.	2007-08-28	2007-08-28
Viracept	Tablet, film coated	625 mg/1	Oral	State of Florida DOH Central Pharmacy	2009-07-01	Not applicable
Viracept -250mg	Tablet	250 mg	Oral	Pfizer	1998-09-21	Not applicable

Categories

UNII

HO3OGH5D7I

CAS number

159989-64-7

Weight

Average: 567.782
Monoisotopic: 567.313077633

Chemical Formula

C₃₂H₄₅N₃O₄S

InChI Key

QAGYKUNXZHXKMR-HKWSIXNMSA-N

InChI

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

IUPAC Name

(3S,4aS,8aS)-N-tert-butyl-2-[(2R,3R)-2-hydroxy-3-[(3-hydroxy-2-methylphenyl)formamido]-4-(phenylsulfanyl)butyl]-decahydroisoquinoline-3-carboxamide

SMILES

[H][C@@]12CCCC[C@]1([H])CN(C[C@@H](O)[C@H](CSC1=CC=CC=C1)NC(=O)C1=C(C)C(O)=CC=C1)[C@@H](C2)C(=O)NC(C)(C)C

Pharmacology

Indication

Used in combination with other antiviral drugs in the treatment of HIV in both adults and children.

Associated Conditions

Infection, Human Immunodeficiency Virus I

Pharmacodynamics

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.

Mechanism of action

Nelfinavir inhibits the HIV viral proteinase enzyme which prevents cleavage of the gag-pol polyprotein, resulting in noninfectious, immature viral particles.

Target	Actions	Organism
AHIV-1 protease	inhibitor	Human Immunodeficiency Virus

Absorption

Well absorbed following oral administration.

Volume of distribution

2 to 7 L/kg

Protein binding

>98%

Metabolism

Primarily hepatic via cytochrome P450 (CYP450) enzymes. CYP3A and CYP2C19 appear to be the predominant enzymes that metabolize nelfinavir in humans. One major and several minor metabolites are found in plasma; the major oxidative metabolite has in vitro antiviral activity comparable to that of the parent drug.

Route of elimination

The terminal half-life in plasma was typically 3.5 to 5 hours. The majority (87%) of an oral 750 mg dose containing 14C-nelfinavir was recovered in the feces; fecal radioactivity consisted of numerous oxidative metabolites (78%) and unchanged nelfinavir (22%). Only 1–2% of the dose was recovered in urine, of which unchanged nelfinavir was the major component.

Half life

3.5 - 5 hours

Clearance

Not Available

Toxicity

Oral LD₅₀ is over 5g/kg in rats. Side effects include thirst and hunger, unexplained weight loss, increased urination, fatigue, and dry, itchy skin.

Affected organisms

Human Immunodeficiency Virus

Pathways

Not Available

Pharmacogenomic Effects/ADRs

Not Available

Interactions

Drug Interactions

Drug	Interaction
(R)-warfarin	The metabolism of (R)-warfarin can be decreased when combined with Nelfinavir.
(S)-Warfarin	The metabolism of (S)-Warfarin can be decreased when combined with Nelfinavir.
2,4-thiazolidinedione	The therapeutic efficacy of 2,4-thiazolidinedione can be decreased when used in combination with Nelfinavir.
3,5-diiodothyropropionic acid	The metabolism of 3,5-diiodothyropropionic acid can be decreased when combined with Nelfinavir.
4-hydroxycoumarin	The metabolism of 4-hydroxycoumarin can be decreased when combined with Nelfinavir.
4-Methoxyamphetamine	The metabolism of 4-Methoxyamphetamine can be decreased when combined with Nelfinavir.
5-androstenedione	The metabolism of 5-androstenedione can be decreased when combined with Nelfinavir.
6-Deoxyerythronolide B	The metabolism of Nelfinavir can be decreased when combined with 6-Deoxyerythronolide B.
6-O-benzylguanine	The metabolism of 6-O-benzylguanine can be decreased when combined with Nelfinavir.
7-ethyl-10-hydroxycamptothecin	The metabolism of 7-ethyl-10-hydroxycamptothecin can be decreased when combined with Nelfinavir.

Food Interactions

Food significantly increases absorption (2 to 3 times).
Take with food.

References

Synthesis Reference

US5461154

General References

Kaldor SW, Kalish VJ, Davies JF 2nd, Shetty BV, Fritz JE, Appelt K, Burgess JA, Campanale KM, Chirgadze NY, Clawson DK, Dressman BA, Hatch SD, Khalil DA, Kosa MB, Lubbehusen PP, Muesing MA, Patick AK, Reich SH, Su KS, Tatlock JH: Viracept (nelfinavir mesylate, AG1343): a potent, orally bioavailable inhibitor of HIV-1 protease. J Med Chem. 1997 Nov 21;40(24):3979-85. [PubMed:9397180]

External Links

Human Metabolome Database: HMDB0014365
KEGG Drug: D08259
KEGG Compound: C07257
PubChem Compound: 64143
PubChem Substance: 46507719
ChemSpider: 57718
BindingDB: 518
ChEBI: 7496
ChEMBL: CHEMBL584
Therapeutic Targets Database: DAP000705
PharmGKB: PA450606
HET: 1UN
RxList: RxList Drug Page
Drugs.com: Drugs.com Drug Page
PDRhealth: PDRhealth Drug Page
Wikipedia: Nelfinavir

ATC Codes

J05AE04 — Nelfinavir

AHFS Codes

08:18.08.08 — HIV Protease Inhibitors

PDB Entries

1ohr / 2pym / 2pyn / 2q63 / 2q64 / 2qak / 2r5q / 3ekx / 3el0 / 3el5

FDA label

Download (294 KB)

MSDS

Download (56.6 KB)

Clinical Trials

Clinical Trials

Phase	Status	Purpose	Conditions	Count
0	Terminated	Treatment	Castleman's Disease / EBV / Kaposi s Sarcoma (KS) / Lymphoma, Hodgkins / Malignant Neoplasm of Nasopharynx / Malignant Neoplasm of Stomach / Non-Hodgkin's Lymphoma (NHL)	1
1	Active Not Recruiting	Treatment	Adenocarcinoma of the Pancreas / Stage III Pancreatic Cancer	1
1	Active Not Recruiting	Treatment	Brain and Central Nervous System Tumors	1
1	Active Not Recruiting	Treatment	Cancer of the Ovary / Carcinoid tumour of the gastrointestinal tract / Colorectal Cancers / Head and Neck Carcinoma / Islet Cell Tumor / Lung Cancers / Metastatic Cancers / Neuroendocrine Carcinoma of the Skin / Pheochromocytomas / Sarcomas / Unspecified Adult Solid Tumor, Protocol Specific	1
1	Active Not Recruiting	Treatment	Lung Cancer Non-Small Cell Cancer (NSCLC)	1
1	Completed	Treatment	Cervical Cancers	1
1	Completed	Treatment	Glioblastomas	1
1	Completed	Treatment	Gliomas	1
1	Completed	Treatment	HIV Seronegativity / Human Immunodeficiency Virus (HIV) Infections / Lipodystrophies	1
1	Completed	Treatment	Healthy Volunteers	1
1	Completed	Treatment	Human Immunodeficiency Virus (HIV) Infections	12
1	Completed	Treatment	Human Immunodeficiency Virus (HIV) Infections / Pregnancy	1
1	Completed	Treatment	Human Immunodeficiency Virus (HIV) Infections / Tuberculosis Infection	1
1	Completed	Treatment	Immune Response	1
1	Completed	Treatment	Leukemias / Malignant Lymphomas / Mature T-cell and Nk-cell Neoplasms / Multiple Myeloma and Plasma Cell Neoplasm	1
1	Completed	Treatment	Malignancies / Renal Cell Adenocarcinoma	1
1	Completed	Treatment	Sepsis	1
1	Completed	Treatment	Tumors, Solid	1
1	Not Yet Recruiting	Treatment	Recurrent Plasma Cell Myeloma / Refractory Plasma Cell Myeloma	1
1	Recruiting	Treatment	Uterine Cervix Cancer	1
1	Terminated	Prevention	Cardiopulmonary Bypass	1
1	Terminated	Treatment	Neoplasms, Pancreatic	1
1	Withdrawn	Treatment	Malignant Lymphomas / Neoplasms	1
1, 2	Active Not Recruiting	Treatment	Lung Cancers	1
1, 2	Active Not Recruiting	Treatment	Multiple Myeloma (MM)	1
1, 2	Completed	Treatment	Carcinoma, Colorectal / Colorectal Cancers / Colorectal Tumors / Neoplasms, Colorectal	1
1, 2	Recruiting	Treatment	Pancreatic Neoplasms (Locally Advanced Non-metastatic)	1
1, 2	Terminated	Treatment	Adult Liposarcoma / Recurrent Adult Soft Tissue Sarcoma / Stage III Adult Soft Tissue Sarcoma / Stage IV Adult Soft Tissue Sarcoma	1
1, 2	Withdrawn	Treatment	Lung Cancers	1
2	Active Not Recruiting	Treatment	Adenocarcinoma of the Pancreas / Resectable Pancreatic Cancers / Resectable Pancreatic Carcinoma / Stage I Pancreatic Cancer / Stage IA Pancreatic Cancer / Stage IB Pancreatic Cancer / Stage II Pancreatic Cancer / Stage IIA Pancreatic Cancer / Stage IIB Pancreatic Cancer / Stage III Pancreatic Cancer	1
2	Active Not Recruiting	Treatment	Oligometastases	1
2	Completed	Treatment	Carcinoma, Adenoid Cystic / Neoplasms, Head and Neck	1
2	Completed	Treatment	Cytomegalovirus Retinitis / Human Immunodeficiency Virus (HIV) Infections	1
2	Completed	Treatment	Human Immunodeficiency Virus (HIV) Infections	16
2	Completed	Treatment	Human Immunodeficiency Virus (HIV) Infections / Infection, Mycobacterium Avium-Intracellulare	1
2	Completed	Treatment	Human Immunodeficiency Virus (HIV) Infections / Kaposi s Sarcoma (KS)	1
2	Completed	Treatment	Plasma Cell Myeloma	1
2	Completed	Treatment	Sarcomas	1
2	Completed	Treatment	Systemic Lupus Erythematosus (SLE)	1
2	Recruiting	Diagnostic	Stage III, IVa, or IVb Squamous Cell Carcinoma of the Oral Cavity, Oropharynx, Larynx, or Hypopharynx	1
2	Recruiting	Treatment	Cervical Dysplasia	1
2	Recruiting	Treatment	Metastatic Renal Cell Cancer / Recurrent Melanoma / Recurrent Non-Small Cell Lung Carcinoma / Renal Cell Carcinoma Recurrent / Stage IV Cutaneous Melanoma AJCC v6 and v7 / Stage IV Non-Small Cell Lung Cancer / Stage IV Non-Small Cell Lung Cancer AJCC v7 / Stage IV Renal Cell Cancer / Stage IV Renal Cell Cancer AJCC V7 / Stage IV Skin Melanoma	1
2	Recruiting	Treatment	Recurrent Kaposi's Sarcoma / Skin Kaposi Sarcoma	1
2	Suspended	Treatment	Human Immunodeficiency Virus (HIV) Infections	2
2	Terminated	Treatment	Lung Cancer Non-Small Cell Cancer (NSCLC)	1
2	Unknown Status	Treatment	Human Immunodeficiency Virus (HIV) Infections	1
2	Withdrawn	Treatment	Human Immunodeficiency Virus (HIV) Infections	1
2, 3	Completed	Treatment	Human Immunodeficiency Virus (HIV) Infections	1
3	Completed	Prevention	Disease Transmission, Vertical / Human Immunodeficiency Virus (HIV) Infections / Vertical Human Immunodeficiency Virus Transmission	1
3	Completed	Treatment	AIDS-Associated Nephropathy / Human Immunodeficiency Virus (HIV) Infections	1
3	Completed	Treatment	Human Immunodeficiency Virus (HIV) Infections	9
3	Completed	Treatment	Human Immunodeficiency Virus (HIV) Infections / Pregnancy	1
3	Not Yet Recruiting	Treatment	Carcinoma Cervix, Stage III	1
3	Terminated	Prevention	Severe or persistent diarrhea	1
3	Terminated	Treatment	Human Immunodeficiency Virus (HIV) Infections	1
3	Unknown Status	Treatment	Human Immunodeficiency Virus (HIV) Infections	3
4	Completed	Diagnostic	Cardiovascular Disease (CVD) / HIV-Associated Lipodystrophy Syndrome	1
4	Completed	Diagnostic	Human Immunodeficiency Virus (HIV) Infections / Lipodystrophies	1
4	Completed	Treatment	Healthy Volunteers	2
4	Completed	Treatment	Human Immunodeficiency Virus (HIV) Infections	2
4	Completed	Treatment	Human Immunodeficiency Virus (HIV) Infections / Tuberculosis Infection	1
4	Unknown Status	Treatment	Human Immunodeficiency Virus (HIV) Infections	1
Not Available	Completed	Treatment	Human Immunodeficiency Virus (HIV) Infections	21
Not Available	Completed	Treatment	Human Immunodeficiency Virus (HIV) Infections / Infection, Mycobacterium Avium-Intracellulare	1
Not Available	Terminated	Treatment	Human Immunodeficiency Virus (HIV) Infections	1

Pharmacoeconomics

Manufacturers

Agouron pharmaceuticals inc

Packagers

Agouron Pharmaceuticals Inc.
A-S Medication Solutions LLC
Cardinal Health
Dept Health Central Pharmacy
Dispensing Solutions
Goedecke GmbH
H.J. Harkins Co. Inc.
Kaiser Foundation Hospital
Lake Erie Medical and Surgical Supply
Patheon Inc.
PD-Rx Pharmaceuticals Inc.
Pfizer Inc.
Physicians Total Care Inc.
Quality Care
Remedy Repack
St Mary's Medical Park Pharmacy
Watson Pharmaceuticals

Dosage forms

Form	Route	Strength
Powder	Oral	50 mg/1g
Tablet	Oral	625 mg
Tablet, film coated	Oral	250 mg/1
Tablet, film coated	Oral	625 mg/1
Tablet	Oral	250 mg
Powder	Oral	50 mg

Prices

Unit description	Cost	Unit
Viracept 625 mg tablet	11.24USD	tablet
Viracept 250 mg tablet	3.46USD	tablet
Viracept 50 mg/gm Powder	0.54USD	gm

DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.

Patents

Patent Number	Pediatric Extension	Approved	Expires (estimated)
US5484926	No	1996-01-16	2014-04-07
CA2173328	No	1999-08-31	2014-10-07

Properties

State

Solid

Experimental Properties

Property	Value	Source
melting point (°C)	349.84 °C	Not Available
water solubility	Slightly soluble	Not Available
logP	6	Not Available

Predicted Properties

Property	Value	Source
Water Solubility	0.00191 mg/mL	ALOGPS
logP	4.61	ALOGPS
logP	4.72	ChemAxon
logS	-5.5	ALOGPS
pKa (Strongest Acidic)	9.32	ChemAxon
pKa (Strongest Basic)	8.18	ChemAxon
Physiological Charge	1	ChemAxon
Hydrogen Acceptor Count	5	ChemAxon
Hydrogen Donor Count	4	ChemAxon
Polar Surface Area	101.9 Å²	ChemAxon
Rotatable Bond Count	10	ChemAxon
Refractivity	162.67 m³·mol^-1	ChemAxon
Polarizability	63.8 Å³	ChemAxon
Number of Rings	4	ChemAxon
Bioavailability	1	ChemAxon
Rule of Five	No	ChemAxon
Ghose Filter	No	ChemAxon
Veber's Rule	No	ChemAxon
MDDR-like Rule	Yes	ChemAxon

Predicted ADMET features

Property	Value	Probability
Human Intestinal Absorption	+	0.7472
Blood Brain Barrier	-	0.9659
Caco-2 permeable	-	0.7148
P-glycoprotein substrate	Substrate	0.9332
P-glycoprotein inhibitor I	Inhibitor	0.8121
P-glycoprotein inhibitor II	Inhibitor	0.7572
Renal organic cation transporter	Non-inhibitor	0.8178
CYP450 2C9 substrate	Non-substrate	0.7482
CYP450 2D6 substrate	Substrate	0.8918
CYP450 3A4 substrate	Substrate	0.7408
CYP450 1A2 substrate	Non-inhibitor	0.9085
CYP450 2C9 inhibitor	Non-inhibitor	0.7994
CYP450 2D6 inhibitor	Non-inhibitor	0.8071
CYP450 2C19 inhibitor	Non-inhibitor	0.6335
CYP450 3A4 inhibitor	Inhibitor	0.5465
CYP450 inhibitory promiscuity	Low CYP Inhibitory Promiscuity	0.8977
Ames test	Non AMES toxic	0.8008
Carcinogenicity	Non-carcinogens	0.8547
Biodegradation	Not ready biodegradable	1.0
Rat acute toxicity	2.4704 LD50, mol/kg	Not applicable
hERG inhibition (predictor I)	Weak inhibitor	0.9786
hERG inhibition (predictor II)	Inhibitor	0.785

ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)

Not Available

Spectra

Spectrum	Spectrum Type	Splash Key
Predicted GC-MS Spectrum - GC-MS	Predicted GC-MS	Not Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)	Predicted LC-MS/MS	Not Available

Taxonomy

Description: This compound belongs to the class of organic compounds known as alpha amino acid amides. These are amide derivatives of alpha amino acids.
Kingdom: Organic compounds
Super Class: Organic acids and derivatives
Class: Carboxylic acids and derivatives
Sub Class: Amino acids, peptides, and analogues
Direct Parent: Alpha amino acid amides
Alternative Parents: o-Toluamides / Piperidinecarboxamides / Benzamides / Thiophenol ethers / Ortho cresols / Benzoyl derivatives / 1-hydroxy-2-unsubstituted benzenoids / 1-hydroxy-4-unsubstituted benzenoids / Alkylarylthioethers / Trialkylamines
show 9 more
Substituents: Alpha-amino acid amide / Piperidinecarboxamide / 2-piperidinecarboxamide / Toluamide / Benzamide / O-toluamide / Benzoic acid or derivatives / Thiophenol ether / O-cresol / Benzoyl
show 31 more
Molecular Framework: Aromatic heteropolycyclic compounds
External Descriptors: tertiary amino compound, secondary alcohol, aryl sulfide, phenols, benzamides, organic heterobicyclic compound (CHEBI:7496)

Targets

Details1. HIV-1 protease

Kind: Protein
Organism: Human Immunodeficiency Virus
Pharmacological action: Yes
Actions: Inhibitor

General Function: Aspartic-type endopeptidase activity
Specific Function: Not Available
Gene Name: HIV-1 protease
Uniprot ID: O90777
Uniprot Name: HIV-1 protease
Molecular Weight: 10724.61 Da

References

Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284]
Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423]
Garriga C, Perez-Elias MJ, Delgado R, Ruiz L, Najera R, Pumarola T, Alonso-Socas Mdel M, Garcia-Bujalance S, Menendez-Arias L: Mutational patterns and correlated amino acid substitutions in the HIV-1 protease after virological failure to nelfinavir- and lopinavir/ritonavir-based treatments. J Med Virol. 2007 Nov;79(11):1617-28. [PubMed:17854027]
Wittayanarakul K, Hannongbua S, Feig M: Accurate prediction of protonation state as a prerequisite for reliable MM-PB(GB)SA binding free energy calculations of HIV-1 protease inhibitors. J Comput Chem. 2008 Apr 15;29(5):673-85. [PubMed:17849388]
Dandache S, Sevigny G, Yelle J, Stranix BR, Parkin N, Schapiro JM, Wainberg MA, Wu JJ: In vitro antiviral activity and cross-resistance profile of PL-100, a novel protease inhibitor of human immunodeficiency virus type 1. Antimicrob Agents Chemother. 2007 Nov;51(11):4036-43. Epub 2007 Jul 16. [PubMed:17638694]
Perez MA, Fernandes PA, Ramos MJ: Drug design: new inhibitors for HIV-1 protease based on Nelfinavir as lead. J Mol Graph Model. 2007 Oct;26(3):634-42. Epub 2007 Mar 24. [PubMed:17459746]
Velazquez-Campoy A, Kiso Y, Freire E: The binding energetics of first- and second-generation HIV-1 protease inhibitors: implications for drug design. Arch Biochem Biophys. 2001 Jun 15;390(2):169-75. [PubMed:11396919]
Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]

Enzymes

Details1. Cytochrome P450 2B6

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Inhibitor

General Function: Steroid hydroxylase activity
Specific Function: Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name: CYP2B6
Uniprot ID: P20813
Uniprot Name: Cytochrome P450 2B6
Molecular Weight: 56277.81 Da

References

Hesse LM, von Moltke LL, Shader RI, Greenblatt DJ: Ritonavir, efavirenz, and nelfinavir inhibit CYP2B6 activity in vitro: potential drug interactions with bupropion. Drug Metab Dispos. 2001 Feb;29(2):100-2. [PubMed:11159797]
Tanabe M, Hashimoto M, Ono H: Imidazoline I(1) receptor-mediated reduction of muscle rigidity in the reserpine-treated murine model of Parkinson's disease. Eur J Pharmacol. 2008 Jul 28;589(1-3):102-5. doi: 10.1016/j.ejphar.2008.06.013. Epub 2008 Jun 7. [PubMed:18602099]
Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
Rendic S: Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448. [PubMed:11996015]
Walsky RL, Astuccio AV, Obach RS: Evaluation of 227 drugs for in vitro inhibition of cytochrome P450 2B6. J Clin Pharmacol. 2006 Dec;46(12):1426-38. [PubMed:17101742]

Details2. Cytochrome P450 2C19

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Substrate
Inhibitor

General Function: Steroid hydroxylase activity
Specific Function: Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and im...
Gene Name: CYP2C19
Uniprot ID: P33261
Uniprot Name: Cytochrome P450 2C19
Molecular Weight: 55930.545 Da

References

Zhou SF, Zhou ZW, Yang LP, Cai JP: 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. Epub 2009 Sep 1. [PubMed:19515014]
Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
Drug Interactions: Cytochrome P450 Drug Interaction Table [Link]

Details3. Cytochrome P450 3A4

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Substrate
Inhibitor

General Function: Vitamin d3 25-hydroxylase activity
Specific Function: Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name: CYP3A4
Uniprot ID: P08684
Uniprot Name: Cytochrome P450 3A4
Molecular Weight: 57342.67 Da

References

Zhou SF, Zhou ZW, Yang LP, Cai JP: 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. Epub 2009 Sep 1. [PubMed:19515014]
Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
Drug Interactions: Cytochrome P450 Drug Interaction Table [Link]
Flockhart Table - Indiana University [Link]

Details4. Cytochrome P450 3A7

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Substrate
Inhibitor

General Function: Oxygen binding
Specific Function: Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name: CYP3A7
Uniprot ID: P24462
Uniprot Name: Cytochrome P450 3A7
Molecular Weight: 57525.03 Da

References

Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
Drug Interactions: Cytochrome P450 Drug Interaction Table [Link]
Flockhart Table - Indiana University [Link]

Details5. Cytochrome P450 3A5

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Inhibitor

General Function: Oxygen binding
Specific Function: Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name: CYP3A5
Uniprot ID: P20815
Uniprot Name: Cytochrome P450 3A5
Molecular Weight: 57108.065 Da

References

Zhou SF, Zhou ZW, Yang LP, Cai JP: 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. Epub 2009 Sep 1. [PubMed:19515014]
Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
Drug Interactions: Cytochrome P450 Drug Interaction Table [Link]
Flockhart Table - Indiana University [Link]

Details6. Cytochrome P450 2D6

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Inhibitor

General Function: Steroid hydroxylase activity
Specific Function: Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic...
Gene Name: CYP2D6
Uniprot ID: P10635
Uniprot Name: Cytochrome P450 2D6
Molecular Weight: 55768.94 Da

References

Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
von Moltke LL, Greenblatt DJ, Duan SX, Daily JP, Harmatz JS, Shader RI: Inhibition of desipramine hydroxylation (Cytochrome P450-2D6) in vitro by quinidine and by viral protease inhibitors: relation to drug interactions in vivo. J Pharm Sci. 1998 Oct;87(10):1184-9. doi: 10.1021/js980197h. [PubMed:9758674]
Lillibridge JH, Liang BH, Kerr BM, Webber S, Quart B, Shetty BV, Lee CA: Characterization of the selectivity and mechanism of human cytochrome P450 inhibition by the human immunodeficiency virus-protease inhibitor nelfinavir mesylate. Drug Metab Dispos. 1998 Jul;26(7):609-16. [PubMed:9660842]

Details7. UDP-glucuronosyltransferase 1-1

Kind: Protein
Organism: Humans
Pharmacological action: No
Actions: Inducer

General Function: Steroid binding
Specific Function: UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This isoform glucuronidates bilirubin IX-alpha to form both the...
Gene Name: UGT1A1
Uniprot ID: P22309
Uniprot Name: UDP-glucuronosyltransferase 1-1
Molecular Weight: 59590.91 Da

References

Interactions [Link]

Details8. Cytochrome P450 2C9

Kind: Protein
Organism: Humans
Pharmacological action: No
Actions: Inhibitor

General Function: Steroid hydroxylase activity
Specific Function: Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name: CYP2C9
Uniprot ID: P11712
Uniprot Name: Cytochrome P450 2C9
Molecular Weight: 55627.365 Da

References

Kirby BJ, Collier AC, Kharasch ED, Dixit V, Desai P, Whittington D, Thummel KE, Unadkat JD: Complex drug interactions of HIV protease inhibitors 2: in vivo induction and in vitro to in vivo correlation of induction of cytochrome P450 1A2, 2B6, and 2C9 by ritonavir or nelfinavir. Drug Metab Dispos. 2011 Dec;39(12):2329-37. doi: 10.1124/dmd.111.038646. Epub 2011 Sep 19. [PubMed:21930825]
Liedtke MD, Rathbun RC: Warfarin-antiretroviral interactions. Ann Pharmacother. 2009 Feb;43(2):322-8. doi: 10.1345/aph.1L497. Epub 2009 Feb 5. [PubMed:19196837]

Carriers

Details1. Serum albumin

Kind: Protein
Organism: Humans
Pharmacological action: Unknown

General Function: Toxic substance binding
Specific Function: Serum albumin, the main protein of plasma, has a good binding capacity for water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs. Its main function is the regulation of the colloid...
Gene Name: ALB
Uniprot ID: P02768
Uniprot Name: Serum albumin
Molecular Weight: 69365.94 Da

References

Bocedi A, Notaril S, Narciso P, Bolli A, Fasano M, Ascenzi P: Binding of anti-HIV drugs to human serum albumin. IUBMB Life. 2004 Oct;56(10):609-14. [PubMed:15814459]
Bocedi A, Notari S, Menegatti E, Fanali G, Fasano M, Ascenzi P: Allosteric modulation of anti-HIV drug and ferric heme binding to human serum albumin. FEBS J. 2005 Dec;272(24):6287-96. [PubMed:16336266]

Transporters

Details1. Multidrug resistance protein 1

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Substrate
Inhibitor
Inducer

General Function: Xenobiotic-transporting atpase activity
Specific Function: Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
Gene Name: ABCB1
Uniprot ID: P08183
Uniprot Name: Multidrug resistance protein 1
Molecular Weight: 141477.255 Da

References

Perloff MD, von Moltke LL, Fahey JM, Daily JP, Greenblatt DJ: Induction of P-glycoprotein expression by HIV protease inhibitors in cell culture. AIDS. 2000 Jun 16;14(9):1287-9. [PubMed:10894301]
Choo EF, Leake B, Wandel C, Imamura H, Wood AJ, Wilkinson GR, Kim RB: Pharmacological inhibition of P-glycoprotein transport enhances the distribution of HIV-1 protease inhibitors into brain and testes. Drug Metab Dispos. 2000 Jun;28(6):655-60. [PubMed:10820137]
Schwab D, Fischer H, Tabatabaei A, Poli S, Huwyler J: Comparison of in vitro P-glycoprotein screening assays: recommendations for their use in drug discovery. J Med Chem. 2003 Apr 24;46(9):1716-25. [PubMed:12699389]
Kim RB, Fromm MF, Wandel C, Leake B, Wood AJ, Roden DM, Wilkinson GR: The drug transporter P-glycoprotein limits oral absorption and brain entry of HIV-1 protease inhibitors. J Clin Invest. 1998 Jan 15;101(2):289-94. [PubMed:9435299]

Details2. Solute carrier family 22 member 1

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Inhibitor

General Function: Secondary active organic cation transmembrane transporter activity
Specific Function: Translocates a broad array of organic cations with various structures and molecular weights including the model compounds 1-methyl-4-phenylpyridinium (MPP), tetraethylammonium (TEA), N-1-methylnico...
Gene Name: SLC22A1
Uniprot ID: O15245
Uniprot Name: Solute carrier family 22 member 1
Molecular Weight: 61153.345 Da

References

Zhang L, Gorset W, Washington CB, Blaschke TF, Kroetz DL, Giacomini KM: Interactions of HIV protease inhibitors with a human organic cation transporter in a mammalian expression system. Drug Metab Dispos. 2000 Mar;28(3):329-34. [PubMed:10681378]
Jung N, Lehmann C, Rubbert A, Schomig E, Fatkenheuer G, Hartmann P, Taubert D: Organic cation transporters OCT1 and OCT2 determine the accumulation of lamivudine in CD4 cells of HIV-infected patients. Infection. 2013 Apr;41(2):379-85. doi: 10.1007/s15010-012-0308-8. Epub 2012 Aug 9. [PubMed:22875535]

Details3. Solute carrier organic anion transporter family member 1A2

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Inhibitor

General Function: Sodium-independent organic anion transmembrane transporter activity
Specific Function: Mediates the Na(+)-independent transport of organic anions such as sulfobromophthalein (BSP) and conjugated (taurocholate) and unconjugated (cholate) bile acids (By similarity). Selectively inhibit...
Gene Name: SLCO1A2
Uniprot ID: P46721
Uniprot Name: Solute carrier organic anion transporter family member 1A2
Molecular Weight: 74144.105 Da

References

Cvetkovic M, Leake B, Fromm MF, Wilkinson GR, Kim RB: OATP and P-glycoprotein transporters mediate the cellular uptake and excretion of fexofenadine. Drug Metab Dispos. 1999 Aug;27(8):866-71. [PubMed:10421612]

Details4. ATP-binding cassette sub-family G member 2

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Inhibitor

General Function: Xenobiotic-transporting atpase activity
Specific Function: High-capacity urate exporter functioning in both renal and extrarenal urate excretion. Plays a role in porphyrin homeostasis as it is able to mediates the export of protoporhyrin IX (PPIX) both fro...
Gene Name: ABCG2
Uniprot ID: Q9UNQ0
Uniprot Name: ATP-binding cassette sub-family G member 2
Molecular Weight: 72313.47 Da

References

Gupta A, Zhang Y, Unadkat JD, Mao Q: HIV protease inhibitors are inhibitors but not substrates of the human breast cancer resistance protein (BCRP/ABCG2). J Pharmacol Exp Ther. 2004 Jul;310(1):334-41. Epub 2004 Mar 8. [PubMed:15007102]

Details5. Solute carrier organic anion transporter family member 1B1

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Inhibitor

General Function: Sodium-independent organic anion transmembrane transporter activity
Specific Function: Mediates the Na(+)-independent uptake of organic anions such as pravastatin, taurocholate, methotrexate, dehydroepiandrosterone sulfate, 17-beta-glucuronosyl estradiol, estrone sulfate, prostagland...
Gene Name: SLCO1B1
Uniprot ID: Q9Y6L6
Uniprot Name: Solute carrier organic anion transporter family member 1B1
Molecular Weight: 76447.99 Da

References

Tirona RG, Leake BF, Wolkoff AW, Kim RB: Human organic anion transporting polypeptide-C (SLC21A6) is a major determinant of rifampin-mediated pregnane X receptor activation. J Pharmacol Exp Ther. 2003 Jan;304(1):223-8. [PubMed:12490595]

Details6. Solute carrier organic anion transporter family member 1B3

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Inhibitor

General Function: Sodium-independent organic anion transmembrane transporter activity
Specific Function: Mediates the Na(+)-independent uptake of organic anions such as 17-beta-glucuronosyl estradiol, taurocholate, triiodothyronine (T3), leukotriene C4, dehydroepiandrosterone sulfate (DHEAS), methotre...
Gene Name: SLCO1B3
Uniprot ID: Q9NPD5
Uniprot Name: Solute carrier organic anion transporter family member 1B3
Molecular Weight: 77402.175 Da

References

Karlgren M, Vildhede A, Norinder U, Wisniewski JR, Kimoto E, Lai Y, Haglund U, Artursson P: Classification of inhibitors of hepatic organic anion transporting polypeptides (OATPs): influence of protein expression on drug-drug interactions. J Med Chem. 2012 May 24;55(10):4740-63. doi: 10.1021/jm300212s. Epub 2012 May 15. [PubMed:22541068]

Details7. Solute carrier organic anion transporter family member 2B1

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Inhibitor

General Function: Sodium-independent organic anion transmembrane transporter activity
Specific Function: Mediates the Na(+)-independent transport of organic anions such as taurocholate, the prostaglandins PGD2, PGE1, PGE2, leukotriene C4, thromboxane B2 and iloprost.
Gene Name: SLCO2B1
Uniprot ID: O94956
Uniprot Name: Solute carrier organic anion transporter family member 2B1
Molecular Weight: 76709.98 Da

References

Karlgren M, Vildhede A, Norinder U, Wisniewski JR, Kimoto E, Lai Y, Haglund U, Artursson P: Classification of inhibitors of hepatic organic anion transporting polypeptides (OATPs): influence of protein expression on drug-drug interactions. J Med Chem. 2012 May 24;55(10):4740-63. doi: 10.1021/jm300212s. Epub 2012 May 15. [PubMed:22541068]

Details8. Bile salt export pump

Kind: Protein
Organism: Humans
Pharmacological action: No
Actions: Substrate

General Function: Transporter activity
Specific Function: Involved in the ATP-dependent secretion of bile salts into the canaliculus of hepatocytes.
Gene Name: ABCB11
Uniprot ID: O95342
Uniprot Name: Bile salt export pump
Molecular Weight: 146405.83 Da

References

Pedersen JM, Matsson P, Bergstrom CA, Hoogstraate J, Noren A, LeCluyse EL, Artursson P: Early identification of clinically relevant drug interactions with the human bile salt export pump (BSEP/ABCB11). Toxicol Sci. 2013 Dec;136(2):328-43. doi: 10.1093/toxsci/kft197. Epub 2013 Sep 6. [PubMed:24014644]

Drug created on June 13, 2005 07:24 / Updated on April 19, 2019 18:54

Nelfinavir

Identification

Structure for Nelfinavir (DB00220)

Pharmacology

Interactions

References

Clinical Trials

Pharmacoeconomics

Properties

Spectra

Taxonomy

Targets

References

Enzymes

References

References

References

References

References

References

References

References

Carriers

References

Transporters

References

References

References

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