U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ABSOLUTE
Molecular Formula C38H50N6O5
Molecular Weight 670.8408
Optical Activity UNSPECIFIED
Defined Stereocenters 6 / 6
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of SAQUINAVIR

SMILES

CC(C)(C)NC(=O)[C@@H]1C[C@@H]2CCCC[C@@H]2CN1C[C@@H](O)[C@H](CC3=CC=CC=C3)NC(=O)[C@H](CC(N)=O)NC(=O)C4=CC=C5C=CC=CC5=N4

InChI

InChIKey=QWAXKHKRTORLEM-UGJKXSETSA-N
InChI=1S/C38H50N6O5/c1-38(2,3)43-37(49)32-20-26-14-7-8-15-27(26)22-44(32)23-33(45)30(19-24-11-5-4-6-12-24)41-36(48)31(21-34(39)46)42-35(47)29-18-17-25-13-9-10-16-28(25)40-29/h4-6,9-13,16-18,26-27,30-33,45H,7-8,14-15,19-23H2,1-3H3,(H2,39,46)(H,41,48)(H,42,47)(H,43,49)/t26-,27+,30-,31-,32-,33+/m0/s1

HIDE SMILES / InChI

Molecular Formula C38H50N6O5
Molecular Weight 670.8408
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry
Defined Stereocenters 6 / 6
E/Z Centers 0
Optical Activity UNSPECIFIED

Description

Saquinavir (brand names Invirase and Fortovase) is an antiretroviral drug used together with other medications to treat or prevent HIV/AIDS. Saquinavir is an inhibitor of HIV protease. HIV protease is an enzyme required for the proteolytic cleavage of viral polyprotein precursors into individual functional proteins found in infectious HIV. Saquinavir is a peptide-like substrate analog that binds to the protease active site and inhibits the activity of the enzyme. Saquinavir inhibition prevents cleavage of the viral polyproteins resulting in the formation of immature noninfectious virus particles. The most frequent adverse events with saquinavir in either formulation are mild gastrointestinal symptoms, including diarrhea, nausea, loose stools & abdominal discomfort. Invirase is better tolerated than Fortovase.

CNS Activity

Originator

Approval Year

PubMed

PubMed

TitleDatePubMed
Synthesis and anti-HIV activity of prodrugs derived from saquinavir and indinavir.
2000 Mar
Tipranavir inhibits broadly protease inhibitor-resistant HIV-1 clinical samples.
2000 Sep 8
Saquinavir soft gelatin capsule: a comparative safety review.
2001
Comparison of P-triglyceride levels among patients with human immunodeficiency virus on randomized treatment with ritonavir, indinavir or ritonavir/saquinavir.
2001
Generation of a flexible cell line with regulatable, high-level expression of HIV Gag/Pol particles capable of packaging HIV-derived vectors.
2001 Apr
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
P-glycoprotein limits oral availability, brain, and fetal penetration of saquinavir even with high doses of ritonavir.
2001 Apr
Determination of serum levels of thirteen human immunodeficiency virus-suppressing drugs by high-performance liquid chromatography.
2001 Apr 13
Determination of interaction kinetic constants for HIV-1 protease inhibitors using optical biosensor technology.
2001 Apr 15
High prevalence of genotypic and phenotypic HIV-1 drug-resistant strains among patients receiving antiretroviral therapy in Abidjan, Côte d'Ivoire.
2001 Apr 15
A phase II trial of dual protease inhibitor therapy: amprenavir in combination with indinavir, nelfinavir, or saquinavir.
2001 Apr 15
[Improving the pharmacokinetics of protease inhibitors in a more innovative manner. HIV drugs administered in a more clever way].
2001 Apr 2
Antiviral drugs: current state of the art.
2001 Aug
Steady-state pharmacokinetics of twice-daily dosing of saquinavir plus ritonavir in HIV-1-infected individuals.
2001 Aug 1
[Resistance to protease inhibitors].
2001 Feb
Pharmacology and clinical experience with saquinavir.
2001 Feb
Switch of protease inhibitor-containing HAART in routine clinical practice: a four-year prospective observational study.
2001 Feb
Effect of alpha1-acid glycoprotein on the intracellular accumulation of the HIV protease inhibitors saquinavir, ritonavir and indinavir in vitro.
2001 Jan
Pilot study of a combination of highly active antiretroviral therapy and cytokines to induce HIV-1 remission.
2001 Jan 1
Efficacy, tolerance, and pharmacokinetics of the combination of stavudine, nevirapine, nelfinavir, and saquinavir as salvage regimen after ritonavir or indinavir failure.
2001 Jan 20
The ADAM study continued: maintenance therapy after 50 weeks of induction therapy.
2001 Jan 5
New developments in anti-HIV chemotherapy.
2001 Jan-Feb
Structure-based design of non-peptide HIV protease inhibitors.
2001 Jan-Feb
Maternal-fetal transfer of saquinavir studied in the ex vivo placental perfusion model.
2001 Jul
HIV protease inhibitors attenuate adherence of Candida albicans to epithelial cells in vitro.
2001 Jul
CMVR diagnoses and progression of CD4 cell counts and HIV viral load measurements in HIV patients on HAART.
2001 Jul
High-performance liquid chromatographic assay to determine the plasma levels of HIV-protease inhibitors (amprenavir, indinavir, nelfinavir, ritonavir and saquinavir) and the non-nucleoside reverse transcriptase inhibitor (nevirapine) after liquid-liquid extraction.
2001 Jul 15
The effects of antiretroviral protease inhibitors on serum lipid levels in HIV-infected patients.
2001 Jun
The effect of fluconazole on ritonavir and saquinavir pharmacokinetics in HIV-1-infected individuals.
2001 Jun
Prognostic factors of combined viral load and CD4+ cell count responses under triple antiretroviral therapy, Aquitaine cohort, 1996-1998.
2001 Jun 1
Effect of ritonavir/saquinavir on stereoselective pharmacokinetics of methadone: results of AIDS Clinical Trials Group (ACTG) 401.
2001 Jun 1
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
Design and synthesis of a conformationally restricted trans peptide isostere based on the bioactive conformations of saquinavir and nelfinavir.
2001 Jun 1
Selection by AZT and rapid replacement in the absence of drugs of HIV type 1 resistant to multiple nucleoside analogs.
2001 Jun 10
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
The binding energetics of first- and second-generation HIV-1 protease inhibitors: implications for drug design.
2001 Jun 15
A comprehensive account on the role of efflux transporters in the gastrointestinal absorption of 13 commonly used substrate drugs in humans.
2001 Mar
Challenges of antiretroviral treatment in transient and drug-using populations: the SUN study.
2001 Mar
Sequencing of protease inhibitor therapy: insights from an analysis of HIV phenotypic resistance in patients failing protease inhibitors.
2001 Mar 30
The interaction of saquinavir (soft gelatin capsule) with ketoconazole, erythromycin and rifampicin: comparison of the effect in healthy volunteers and in HIV-infected patients.
2001 May
Structure-activity studies of FIV and HIV protease inhibitors containing allophenylnorstatine.
2001 May
Secreted aspartic proteases of Candida albicans, Candida tropicalis, Candida parapsilosis and Candida lusitaniae. Inhibition with peptidomimetic inhibitors.
2001 May
Regulation of expression of 11beta-hydroxysteroid dehydrogenase type 1 in adipose tissue: tissue-specific induction by cytokines.
2001 May
Clinical outcome among HIV-infected patients starting saquinavir hard gel compared to ritonavir or indinavir.
2001 May 25
Increased risk of lipodystrophy when nucleoside analogue reverse transcriptase inhibitors are included with protease inhibitors in the treatment of HIV-1 infection.
2001 May 4
Simultaneous determination of the HIV protease inhibitors indinavir, amprenavir, saquinavir, ritonavir and nelfinavir in human plasma by high-performance liquid chromatography.
2001 May 5
Combined hydroxypropyl-beta-cyclodextrin and poly(alkylcyanoacrylate) nanoparticles intended for oral administration of saquinavir.
2001 May 7
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
Novel low molecular weight spirodiketopiperazine derivatives potently inhibit R5 HIV-1 infection through their antagonistic effects on CCR5.
2001 Sep 14
Peptide mimetic HIV protease inhibitors are ligands for the orphan receptor SXR.
2001 Sep 7
Patents

Sample Use Guides

In Vivo Use Guide
1000 mg (with ritonavir 100 mg) PO q12hr, or in combination with ritonavir-enhanced lopinavir Treatment-naïve patients: Initial dose: 500 mg PO BID plus ritonavir 100 mg BID x 7 days, THEN increase to 1000mg/100mg PO BID
Route of Administration: Oral
In Vitro Use Guide
In vitro antiviral activity of saquinavir was assessed in lymphoblastoid and monocytic cell lines and in peripheral blood lymphocytes. Saquinavir inhibited HIV activity in both acutely and chronically infected cells. IC50 and IC90 values (50% and 90% inhibitory concentrations) were in the range of 1 to 30 nM and 5 to 80 nM, respectively. In the presence of 40% human serum, the mean IC50 of saquinavir against laboratory strain HIV-1 RF in MT4 cells was 37.7± 5nM representing a 4-fold increase in the IC50 value. In cell culture, saquinavir demonstrated additive to synergistic effects against HIV-1 in combination with reverse transcriptase inhibitors (didanosine, lamivudine, nevirapine, stavudine, zalcitabine and zidovudine) without enhanced cytotoxicity. Saquinavir in combination with the protease inhibitors amprenavir, atazanavir, or lopinavir resulted in synergistic antiviral activity. Saquinavir displayed antiviral activity in vitro against HIV-1 clades A-H (IC50 ranged from 0.9 to 2.5 nM). The IC50 and IC90 values of saquinavir against HIV-2 isolates in vitro ranged from 0.25 nM to 14.6 nM and 4.65 nM to 28.6 nM respectively.
Substance Class Chemical
Created
by admin
on Mon Oct 21 19:47:03 UTC 2019
Edited
by admin
on Mon Oct 21 19:47:03 UTC 2019
Record UNII
L3JE09KZ2F
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
SAQUINAVIR
EMA EPAR   HSDB   INN   JAN   MART.   MI   ORANGE BOOK   USAN   USP   VANDF   WHO-DD   WHO-IP  
USAN   INN  
Official Name English
RO 31-8959/000
Code English
SAQUINAVIR [JAN]
Common Name English
SAQUINAVIRUM [WHO-IP LATIN]
Common Name English
SAQUINAVIR [ORANGE BOOK]
Common Name English
SAQUINAVIR [VANDF]
Common Name English
SAQUINAVIR [USAN]
Common Name English
SAQUINAVIR [HSDB]
Common Name English
RO-31-8959/000
Code English
BUTANEDIAMIDE, N(SUP 1)-(3-(3-(((1,1-DIMETHYLETHYL)AMINO)CARBONYL)OCTAHYDRO-2(1H)-ISOQUINOLINYL)-2-HYDROXY-1-(PHENYLMETHYL)PROPYL)-2-((2-QUINOLINYLCARBONYL)AMINO)-, (3S-(2(1R*(R*),2S*),3.ALPHA.,4A.BETA.,8A.BETA.))-
Common Name English
(S)-N-((IS)-I-((1R)-2-((3S,4AS,8AS)-3-(TERT-BUTYLCARBAMOYL)OCTAHYDRO-2(1H)-ISOQUINOLYL)-1-HYDROXYETHYL)PHENETHYL)-2-QUINALDAMIDOSUCCINAMIDE
Common Name English
SAQUINAVIR [USP]
Common Name English
SAQUINAVIR [WHO-IP]
Common Name English
SAQUINAVIR [WHO-DD]
Common Name English
SAQUINAVIR [EMA EPAR]
Common Name English
(S)-N-((.ALPHA.S)-.ALPHA.-((1R)-2-((3S,4AS,8AS)-3-(TERT-BUTYLCARBAMOYL)OCTAHYDRO-2(1H)-ISOQUINOLYL)-1-HYDROXYETHYL)PHENETHYL)-2-QUINALDAMIDOSUCCINAMIDE
Common Name English
SAQUINAVIR [INN]
Common Name English
SAQUINAVIR [MART.]
Common Name English
SCH-52852
Code English
SAQUINAVIR [MI]
Common Name English
Classification Tree Code System Code
NDF-RT N0000175889
Created by admin on Mon Oct 21 19:47:03 UTC 2019 , Edited by admin on Mon Oct 21 19:47:03 UTC 2019
NDF-RT N0000000246
Created by admin on Mon Oct 21 19:47:03 UTC 2019 , Edited by admin on Mon Oct 21 19:47:03 UTC 2019
WHO-VATC QJ05AE01
Created by admin on Mon Oct 21 19:47:03 UTC 2019 , Edited by admin on Mon Oct 21 19:47:03 UTC 2019
EMA ASSESSMENT REPORTS INVIRASE (AUHTORIZED: HIV INFECTIONS)
Created by admin on Mon Oct 21 19:47:03 UTC 2019 , Edited by admin on Mon Oct 21 19:47:03 UTC 2019
EMA ASSESSMENT REPORTS FORTOVASE (WITHDRAWN: HIV INFECTIONS)
Created by admin on Mon Oct 21 19:47:03 UTC 2019 , Edited by admin on Mon Oct 21 19:47:03 UTC 2019
WHO-ESSENTIAL MEDICINES LIST 6.4.2.3
Created by admin on Mon Oct 21 19:47:03 UTC 2019 , Edited by admin on Mon Oct 21 19:47:03 UTC 2019
WHO-ATC J05AE01
Created by admin on Mon Oct 21 19:47:03 UTC 2019 , Edited by admin on Mon Oct 21 19:47:03 UTC 2019
NCI_THESAURUS C97366
Created by admin on Mon Oct 21 19:47:03 UTC 2019 , Edited by admin on Mon Oct 21 19:47:03 UTC 2019
LIVERTOX 871
Created by admin on Mon Oct 21 19:47:03 UTC 2019 , Edited by admin on Mon Oct 21 19:47:03 UTC 2019
Code System Code Type Description
INN
7098
Created by admin on Mon Oct 21 19:47:03 UTC 2019 , Edited by admin on Mon Oct 21 19:47:03 UTC 2019
PRIMARY
LactMed
127779-20-8
Created by admin on Mon Oct 21 19:47:03 UTC 2019 , Edited by admin on Mon Oct 21 19:47:03 UTC 2019
PRIMARY
NCI_THESAURUS
C29444
Created by admin on Mon Oct 21 19:47:03 UTC 2019 , Edited by admin on Mon Oct 21 19:47:03 UTC 2019
PRIMARY
IUPHAR
4813
Created by admin on Mon Oct 21 19:47:03 UTC 2019 , Edited by admin on Mon Oct 21 19:47:03 UTC 2019
PRIMARY
DRUG BANK
DB01232
Created by admin on Mon Oct 21 19:47:03 UTC 2019 , Edited by admin on Mon Oct 21 19:47:03 UTC 2019
PRIMARY
WIKIPEDIA
SAQUINAVIR
Created by admin on Mon Oct 21 19:47:03 UTC 2019 , Edited by admin on Mon Oct 21 19:47:03 UTC 2019
PRIMARY
WHO INTERNATIONAL PHARMACOPEIA
SAQUINAVIR
Created by admin on Mon Oct 21 19:47:03 UTC 2019 , Edited by admin on Mon Oct 21 19:47:03 UTC 2019
PRIMARY Description: A white or almost white powder. Solubility: Practically insoluble in water and soluble in methanol. Category: Antiretroviral (Protease Inhibitor). Storage: Saquinavir should be kept at 2-8?C in a tightly closed container, protected from light. Additional information: Saquinavir is slightly hygroscopic. Requirements: Saquinavir contains not less than 98.5 % and not more than 101.0 % of C38H50N6O5, calculated with reference to the dried substance.
ChEMBL
CHEMBL114
Created by admin on Mon Oct 21 19:47:03 UTC 2019 , Edited by admin on Mon Oct 21 19:47:03 UTC 2019
PRIMARY
NDF-RT
N0000190114
Created by admin on Mon Oct 21 19:47:03 UTC 2019 , Edited by admin on Mon Oct 21 19:47:03 UTC 2019
PRIMARY Cytochrome P450 3A Inhibitors [MoA]
EVMPD
SUB10446MIG
Created by admin on Mon Oct 21 19:47:03 UTC 2019 , Edited by admin on Mon Oct 21 19:47:03 UTC 2019
PRIMARY
RXCUI
83395
Created by admin on Mon Oct 21 19:47:03 UTC 2019 , Edited by admin on Mon Oct 21 19:47:03 UTC 2019
PRIMARY RxNorm
PUBCHEM
441243
Created by admin on Mon Oct 21 19:47:03 UTC 2019 , Edited by admin on Mon Oct 21 19:47:03 UTC 2019
PRIMARY
MERCK INDEX
M9776
Created by admin on Mon Oct 21 19:47:03 UTC 2019 , Edited by admin on Mon Oct 21 19:47:03 UTC 2019
PRIMARY Merck Index
MESH
D019258
Created by admin on Mon Oct 21 19:47:03 UTC 2019 , Edited by admin on Mon Oct 21 19:47:03 UTC 2019
PRIMARY
EPA CompTox
127779-20-8
Created by admin on Mon Oct 21 19:47:03 UTC 2019 , Edited by admin on Mon Oct 21 19:47:03 UTC 2019
PRIMARY
HSDB
127779-20-8
Created by admin on Mon Oct 21 19:47:03 UTC 2019 , Edited by admin on Mon Oct 21 19:47:03 UTC 2019
PRIMARY
CAS
127779-20-8
Created by admin on Mon Oct 21 19:47:03 UTC 2019 , Edited by admin on Mon Oct 21 19:47:03 UTC 2019
PRIMARY
Related Record Type Details
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TRANSPORTER -> INHIBITOR
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SUBSTRATE USED: ESTRONE-3-SULFATE
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BINDER->LIGAND
BINDING
METABOLIC ENZYME -> SUBSTRATE
SALT/SOLVATE -> PARENT
TRANSPORTER -> SUBSTRATE
TRANSPORTER -> INHIBITOR
METABOLIC ENZYME -> SUBSTRATE
TRANSPORTER -> INHIBITOR
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ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
Volume of Distribution PHARMACOKINETIC