saquinavir 🐶 Veterinary Use | Indications/Contra | FAERs-F | FAERs-M | Orange Bk | PK/Tox | Related Drugs | BioActivity |

Stem definitionDrug idCAS RN
HIV protease inhibitors 2422 127779-20-8

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • invirase
  • saquinavir methanesulfonate
  • saquinavir
  • sequinavir
  • fortovase
  • saquinavir mesylate
  • saquinavir mesilate
An HIV protease inhibitor which acts as an analog of an HIV protease cleavage site. It is a highly specific inhibitor of HIV-1 and HIV-2 proteases, and also inhibits CYTOCHROME P-450 CYP3A. There was some evidence of in vitro activity against SARS-CoV-2, but no clinical trial data was found to support use in the treatment of COVID-19.
  • Molecular weight: 670.86
  • Formula: C38H50N6O5
  • CLOGP: 4.73
  • LIPINSKI: 2
  • HAC: 11
  • HDO: 5
  • TPSA: 166.75
  • ALOGS: -5.43
  • ROTB: 13
  • Status: OFM
    • Legend:
    OFP - off patent
    OFM - off market
    ONP - on patent

Drug dosage:

DoseUnitRoute
1.80 g O

ADMET properties:

PropertyValueReference
BDDCS (Biopharmaceutical Drug Disposition Classification System) 2 Benet LZ, Broccatelli F, Oprea TI
S (Water solubility) 0.08 mg/mL Benet LZ, Broccatelli F, Oprea TI
EoM (Fraction excreted unchanged in urine) 2 % Benet LZ, Broccatelli F, Oprea TI
Vd (Volume of distribution) 3.60 L/kg Lombardo F, Berellini G, Obach RS
CL (Clearance) 13 mL/min/kg Lombardo F, Berellini G, Obach RS
fu (Fraction unbound in plasma) 0.03 % Lombardo F, Berellini G, Obach RS
t_half (Half-life) 13 hours Lombardo F, Berellini G, Obach RS
BA (Bioavailability) 5 %

Predicted pharmacokinetic/toxicological properties (PK-AZ):

PropertyDescriptionValueUnitConfidenceSimilarity
mdck-mdr1-bcrp-efflux MDCK-MDR1-BCRP efflux ratio 41.591 High 1
pfas-class PFAS structural alert (1 = True, 0 = False) 0
rat-kpuu-brain Rat brain Kpuu 0.013 % High 1

Approvals:

DateAgencyCompanyOrphan
Dec. 6, 1995 FDA HOFFMANN LA ROCHE
Oct. 3, 1996 EMA ROCHE REGISTRATION GMBH

FDA Adverse Event Reporting System (Female)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Viral mutation identified 194.11 81.72 28 436 1997 90625986
Drug resistance 139.65 81.72 32 432 30417 90597566
Genotype drug resistance test positive 82.34 81.72 11 453 438 90627545

FDA Adverse Event Reporting System (Male)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Lipodystrophy acquired 839.44 54.02 143 1765 3307 42616120
Mitochondrial toxicity 758.01 54.02 126 1782 2489 42616938
Eyelid ptosis 646.49 54.02 127 1781 6534 42612893
Diplopia 485.47 54.02 123 1785 20193 42599234
Progressive external ophthalmoplegia 401.02 54.02 67 1841 1344 42618083
Ophthalmoplegia 170.98 54.02 35 1873 2165 42617262
Dysphagia 133.88 54.02 65 1843 72654 42546773
Virologic failure 124.09 54.02 30 1878 3964 42615463
Pathogen resistance 96.93 54.02 31 1877 11419 42608008
Viral mutation identified 93.17 54.02 23 1885 3308 42616119
Multiple-drug resistance 62.65 54.02 20 1888 7302 42612125
Blood lactic acid increased 60.82 54.02 20 1888 8019 42611408
Dyslipidaemia 57.71 54.02 20 1888 9398 42610029

FDA Adverse Event Reporting System (Geriatric)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Lipodystrophy acquired 886.89 60.05 139 2050 4385 110582725
Mitochondrial toxicity 833.03 60.05 126 2063 3119 110583991
Eyelid ptosis 655.22 60.05 126 2063 13201 110573909
Diplopia 491.18 60.05 122 2067 41772 110545338
Progressive external ophthalmoplegia 455.08 60.05 67 2122 1353 110585757
Viral mutation identified 255.38 60.05 48 2141 4371 110582739
Drug resistance 193.11 60.05 63 2126 56311 110530799
Ophthalmoplegia 176.52 60.05 34 2155 3516 110583594
Virologic failure 159.38 60.05 33 2156 4919 110582191
Dysphagia 137.98 60.05 65 2124 153535 110433575
Pathogen resistance 99.65 60.05 29 2160 17643 110569467
Multiple-drug resistance 80.31 60.05 23 2166 13212 110573898
Blood HIV RNA increased 78.69 60.05 16 2173 2172 110584938
Dyslipidaemia 67.54 60.05 21 2168 15944 110571166
Genotype drug resistance test positive 60.86 60.05 12 2177 1394 110585716

FDA Adverse Event Reporting System (Pediatric)

None

Pharmacologic Action:

SourceCodeDescription
ATC J05AE01 ANTIINFECTIVES FOR SYSTEMIC USE
ANTIVIRALS FOR SYSTEMIC USE
DIRECT ACTING ANTIVIRALS
Protease inhibitors
FDA MoA N0000000246 HIV Protease Inhibitors
FDA EPC N0000175889 Protease Inhibitor
FDA MoA N0000190114 Cytochrome P450 3A Inhibitors
MeSH PA D000890 Anti-Infective Agents
MeSH PA D000998 Antiviral Agents
MeSH PA D004791 Enzyme Inhibitors
MeSH PA D011480 Protease Inhibitors
MeSH PA D017320 HIV Protease Inhibitors
MeSH PA D019380 Anti-HIV Agents
MeSH PA D065607 Cytochrome P-450 Enzyme Inhibitors
MeSH PA D065692 Cytochrome P-450 CYP3A Inhibitors
CHEBI has role CHEBI:35610 antineoplastic agent
CHEBI has role CHEBI:64946 anti-HIV agent
CHEBI has role CHEBI:22587 antiviral agent
CHEBI has role CHEBI:35660 HIV protease inhibitor
CHEBI has role CHEBI:35674 antihypertensive agent
CHEBI has role CHEBI:36044 antiviral drug

Related Drugs by ATC class:

J05AE Protease inhibitors 10 drugs
amprenaviratazanavirdarunavirensitrelvirfosamprenavirindinavirnelfinavirnirmatrelvirritonavirtipranavir

Drug Use | Suggest Off label Use Form| |View source of the data|

DiseaseRelationSNOMED_IDDOID
Human immunodeficiency virus infection indication 86406008 DOID:526
Alcoholism contraindication 7200002
Hypercholesterolemia contraindication 13644009
Cirrhosis of liver contraindication 19943007 DOID:5082
Complete atrioventricular block contraindication 27885002
Hereditary factor VIII deficiency disease contraindication 28293008 DOID:12134
Torsades de pointes contraindication 31722008
Hereditary factor IX deficiency disease contraindication 41788008 DOID:12259
Hypokalemia contraindication 43339004
Viral hepatitis C contraindication 50711007 DOID:1883
Hepatic failure contraindication 59927004
Chronic type B viral hepatitis contraindication 61977001
Diabetes mellitus contraindication 73211009 DOID:9351
Hyperglycemia contraindication 80394007 DOID:4195
Prolonged QT interval contraindication 111975006
Chronic hepatitis C contraindication 128302006
Liver function tests abnormal contraindication 166603001
Hypomagnesemia contraindication 190855004
Second degree atrioventricular block contraindication 195042002
Disease of liver contraindication 235856003 DOID:409
Hypertriglyceridemia contraindication 302870006
Breastfeeding (mother) contraindication 413712001
Congenital long QT syndrome contraindication 442917000




🐶 Veterinary Drug Use

None

🐶 Veterinary products

None

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation levelDissociation constantType (acidic/basic)
pKa1 11.89 acidic
pKa2 12.53 acidic
pKa3 12.89 acidic
pKa4 7.46 Basic
pKa5 4.9 Basic

Orange Book patent data (new drug applications)

None

Orange Book exclusivity data (new drug applications)

None

Bioactivity Summary:

TargetClassPharosUniProtActionTypeActivity value
(-log[M])		Mechanism
action		Bioact sourceMoA source
Cytochrome P450 3A4 Enzyme IC50 5.82 WOMBAT-PK
Multidrug resistance protein 1 Transporter IC50 4.92 WOMBAT-PK
5-hydroxytryptamine receptor 1A GPCR Ki 5.61 DRUG MATRIX
D(3) dopamine receptor GPCR Ki 5.28 DRUG MATRIX
Canalicular multispecific organic anion transporter 1 Transporter IC50 4.70 WOMBAT-PK
Sodium-dependent dopamine transporter Transporter Ki 4.56 DRUG MATRIX
Kappa-type opioid receptor GPCR Ki 5.56 DRUG MATRIX
Multidrug resistance-associated protein 1 Transporter WOMBAT-PK
ATP-binding cassette sub-family G member 2 Transporter IC50 4.71 CHEMBL
Delta-type opioid receptor GPCR Ki 5.00 DRUG MATRIX
Vasopressin V1a receptor GPCR Ki 5.15 DRUG MATRIX
Thromboxane-A synthase Enzyme IC50 5.66 DRUG MATRIX
Substance-K receptor GPCR Ki 5.68 DRUG MATRIX
Mu-type opioid receptor GPCR Ki 5.41 DRUG MATRIX
Pol polyprotein Enzyme INHIBITOR Ki 10.40 CHEMBL CHEMBL
Gag-Pol polyprotein Polyprotein Ki 10.19 WOMBAT-PK
5-hydroxytryptamine receptor 1A GPCR IC50 5.37 CHEMBL
Protease Enzyme IC50 9.30 CHEMBL
Protease Enzyme Ki 10.40 CHEMBL
Chloroquine resistance transporter Transporter IC50 4.89 CHEMBL
Replicase polyprotein 1ab Enzyme IC50 5 CHEMBL
Protease Enzyme Ki 9.66 CHEMBL
Protease Enzyme Ki 8.54 CHEMBL

External reference:

IDSource
D00429 KEGG_DRUG
149845-06-7 SECONDARY_CAS_RN
4020939 VANDF
4021118 VANDF
C0286738 UMLSCUI
CHEBI:63621 CHEBI
ROC PDB_CHEM_ID
CHEMBL114 ChEMBL_ID
CHEMBL282042 ChEMBL_ID
D019258 MESH_DESCRIPTOR_UI
DB01232 DRUGBANK_ID
4813 IUPHAR_LIGAND_ID
C508896 MESH_SUPPLEMENTAL_RECORD_UI
7098 INN_ID
L3JE09KZ2F UNII
441243 PUBCHEM_CID
203674 RXNORM
11448 MMSL
16538 MMSL
5146 MMSL
5442 MMSL
7880 MMSL
d03860 MMSL
005089 NDDF
005090 NDDF
108700005 SNOMEDCT_US
108701009 SNOMEDCT_US
372530001 SNOMEDCT_US

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
Invirase HUMAN PRESCRIPTION DRUG LABEL 1 53808-0674 TABLET, FILM COATED 500 mg ORAL NDA 26 sections