tipranavir ๐Ÿถ Veterinary Use | Indications/Contra | FAERs-F | FAERs-M | Orange Bk | PK/Tox | Related Drugs | BioActivity |

Stem definitionDrug idCAS RN
HIV protease inhibitors 3609 174484-41-4

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • tipranavir
  • aptivus
  • PNU-140690
  • PNU 140690
Tipranavir is an HIV-1 protease inhibitor that inhibits the virus-specific processing of the viral Gag and Gag-Pol polyproteins in HIV-1 infected cells, thus preventing formation of mature virions. 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: 602.67
  • Formula: C31H33F3N2O5S
  • CLOGP: 7.76
  • LIPINSKI: 2
  • HAC: 7
  • HDO: 2
  • TPSA: 105.59
  • ALOGS: -6.47
  • ROTB: 11

  • Status: OFP

  • Legend:
    OFP - off patent
    OFM - off market
    ONP - on patent

Drug dosage:

DoseUnitRoute
1 g O

ADMET properties:

PropertyValueReference
BDDCS (Biopharmaceutical Drug Disposition Classification System) 2 Benet LZ, Broccatelli F, Oprea TI
EoM (Fraction excreted unchanged in urine) 0.10 % Benet LZ, Broccatelli F, Oprea TI
MRTD (Maximum Recommended Therapeutic Daily Dose) 23.70 ยตM/kg/day Contrera JF, Matthews EJ, Kruhlak NL, Benz RD

Predicted pharmacokinetic/toxicological properties (PK-AZ):

PropertyDescriptionValueUnitConfidenceSimilarity
kinase-safety-class ACVR2A,ACVR2B,AURKA,AXL,BRAF,BTK,CAMK2D,CDK5,CDK9,DYRK1B,EGFR,EIF2AK3,ERBB2,GRK2,GSK3B,IKBKB,ITK,JAK2,JAK3,MAP2K6,MAP3K7,MAPK10,MAPK7,MAPK8,MAPK9,MAPKAPK2,NTRK2,PDK1,PDK2,PDK4,PDPK1,PIK3CA,PIK3CB,PIK3CD,PIK3CG,PIM2,PRKDC,STK33,SYK,TEK,TTK,ZAP70 42
kinase-selectivity-class AXL,GRK2,MAP2K6,PDK4,TEK 5
pfas-class PFAS structural alert (1 = True, 0 = False) 1
pld-class Phospholipidosis risk class (1 = positive, 0 = negative) 1 Moderate 0.72

Approvals:

DateAgencyCompanyOrphan
June 22, 2005 FDA BOEHRINGER INGELHEIM

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
Schizophrenia 1101.05 320.47 227 3869 14687 90609664
Cholelithiasis 816.95 320.47 227 3869 52279 90572072
Hypomania 789.31 320.47 158 3938 8739 90615612
Jaundice cholestatic 717.46 320.47 149 3947 9894 90614457
Psychotic disorder 544.65 320.47 148 3948 31082 90593269
Hepatotoxicity 514.44 320.47 154 3942 45688 90578663
Blood bilirubin increased 500.60 320.47 149 3947 43321 90581030
Asthma-chronic obstructive pulmonary disease overlap syndrome 451.89 320.47 90 4006 4809 90619542
Total lung capacity increased 449.68 320.47 90 4006 4931 90619420
Sarcoidosis 382.06 320.47 90 4006 10583 90613768
Nasal polyps 380.35 320.47 90 4006 10790 90613561
Rhinitis allergic 341.59 320.47 90 4006 16695 90607656
Cardiac murmur 334.39 320.47 90 4006 18104 90606247

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
Virologic failure 100.23 44.87 22 900 3972 42616441
Acquired immunodeficiency syndrome 86.22 44.87 14 908 494 42619919
Multiple-drug resistance 58.14 44.87 16 906 7306 42613107
Dyschromatopsia 57.42 44.87 10 912 539 42619874
Viral mutation identified 54.70 44.87 13 909 3318 42617095
Drug resistance 50.20 44.87 21 901 34227 42586186
HIV infection 47.49 44.87 10 912 1475 42618938
Viral load increased 45.60 44.87 11 911 2986 42617427

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
Schizophrenia 1068.98 123.86 231 4110 21595 110563363
Cholelithiasis 828.71 123.86 232 4109 63190 110521768
Hypomania 801.70 123.86 160 4181 10050 110574908
Jaundice cholestatic 693.80 123.86 151 4190 14457 110570501
Psychotic disorder 510.94 123.86 152 4189 50785 110534173
Hepatotoxicity 494.78 123.86 156 4185 63244 110521714
Total lung capacity increased 472.95 123.86 92 4249 5020 110579938
Blood bilirubin increased 455.09 123.86 153 4188 75819 110509139
Asthma-chronic obstructive pulmonary disease overlap syndrome 453.13 123.86 92 4249 6252 110578706
Sarcoidosis 390.39 123.86 92 4249 12487 110572471
Nasal polyps 385.98 123.86 92 4249 13108 110571850
Rhinitis allergic 358.03 123.86 92 4249 17830 110567128
Cardiac murmur 329.05 123.86 92 4249 24536 110560422
Bronchiectasis 293.32 123.86 92 4249 36401 110548557
Vomiting 257.67 123.86 240 4101 910435 109674523
Hepatic enzyme increased 254.12 123.86 157 4184 320735 110264223
Pneumonia 251.70 123.86 233 4108 876481 109708477
Lung neoplasm malignant 241.68 123.86 78 4263 33764 110551194
Nausea 206.54 123.86 246 4095 1235444 109349514
Chronic obstructive pulmonary disease 195.32 123.86 92 4249 109066 110475892
Gastrooesophageal reflux disease 152.04 123.86 92 4249 179884 110405074
Condition aggravated 127.87 123.86 150 4191 734686 109850272
Wheezing 125.04 123.86 93 4248 255137 110329821

FDA Adverse Event Reporting System (Pediatric)

None

Pharmacologic Action:

SourceCodeDescription
ATC J05AE09 ANTIINFECTIVES FOR SYSTEMIC USE
ANTIVIRALS FOR SYSTEMIC USE
DIRECT ACTING ANTIVIRALS
Protease inhibitors
FDA MoA N0000000246 HIV Protease Inhibitors
MeSH PA D000890 Anti-Infective Agents
MeSH PA D000998 Antiviral Agents
MeSH PA D019380 Anti-HIV Agents
MeSH PA D044966 Anti-Retroviral Agents
FDA EPC N0000175889 Protease Inhibitor
CHEBI has role CHEBI:22587 antiviral agent
CHEBI has role CHEBI:35660 HIV protease inhibitor
CHEBI has role CHEBI:36044 antiviral drug
CHEBI has role CHEBI:64946 anti-HIV agent

Related Drugs by ATC class:

J05AE Protease inhibitors 10 drugs

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

DiseaseRelationSNOMED_IDDOID
Human immunodeficiency virus infection indication 86406008 DOID:526
Intracranial hemorrhage contraindication 1386000
Hypercholesterolemia contraindication 13644009
Hyperbilirubinemia contraindication 14783006 DOID:2741
Hereditary factor VIII deficiency disease contraindication 28293008 DOID:12134
Hereditary factor IX deficiency disease contraindication 41788008 DOID:12259
Hepatic failure contraindication 59927004
Chronic type B viral hepatitis contraindication 61977001
Blood coagulation disorder contraindication 64779008 DOID:1247
Diabetes mellitus contraindication 73211009 DOID:9351
Hyperglycemia contraindication 80394007 DOID:4195
Procedure on central nervous system contraindication 118679007
Neoplasm of brain contraindication 126952004 DOID:1319
Inflammatory disease of liver contraindication 128241005
Chronic hepatitis C contraindication 128302006
Liver function tests abnormal contraindication 166603001
Disease of liver contraindication 235856003 DOID:409
Lesion of brain contraindication 301766008
Hypertriglyceridemia contraindication 302870006
Surgical procedure contraindication 387713003
Breastfeeding (mother) contraindication 413712001
Traumatic injury contraindication 417746004




๐Ÿถ Veterinary Drug Use

None

๐Ÿถ Veterinary products

None

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation levelDissociation constantType (acidic/basic)
pKa1 5.13 acidic
pKa2 6.12 acidic

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
Cathepsin D Enzyme Ki 4.82 CHEMBL
Multidrug resistance protein 1 Transporter WOMBAT-PK
Cathepsin E Enzyme Ki 5.05 CHEMBL
Pepsin A-5 Enzyme Ki 5.70 CHEMBL
Pol polyprotein Enzyme INHIBITOR IC50 7.52 CHEMBL CHEMBL
Replicase polyprotein 1ab Enzyme IC50 5.13 CHEMBL
CAAX prenyl protease 1 homolog Enzyme IC50 5.92 CHEMBL

External reference:

IDSource
4024917 VUID
N0000171602 NUI
D08605 KEGG_DRUG
4024917 VANDF
C0663733 UMLSCUI
CHEBI:63628 CHEBI
TPV PDB_CHEM_ID
CHEMBL222559 ChEMBL_ID
DB00932 DRUGBANK_ID
C107201 MESH_SUPPLEMENTAL_RECORD_UI
12685 IUPHAR_LIGAND_ID
7774 INN_ID
ZZT404XD09 UNII
54682461 PUBCHEM_CID
190548 RXNORM
20182 MMSL
69882 MMSL
d05538 MMSL
010844 NDDF
418721002 SNOMEDCT_US
419409009 SNOMEDCT_US

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
Aptivus HUMAN PRESCRIPTION DRUG LABEL 1 0597-0003 CAPSULE, LIQUID FILLED 250 mg ORAL NDA 33 sections