tipranavir Indications/Contra | FAERs-F | FAERs-M | Orange Bk | BioActivity |

Stem definition	Drug id	CAS RN
HIV protease inhibitors	3609	174484-41-4

Description:

Molecule	Description
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

Molecule

Description

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:

Dose	Unit	Route
1	g	O

ADMET properties:

Property	Value	Reference
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 µM/kg/day	Contrera JF, Matthews EJ, Kruhlak NL, Benz RD

Approvals:

Date	Agency	Company	Orphan
June 22, 2005	FDA	BOEHRINGER INGELHEIM

FDA Adverse Event Reporting System (Female)

MedDRA adverse event term	Likelihood ratio	Likelihood ratio threshold	Patients taking drug having adverse event	Patients taking drug not having adverse event	Patients not taking drug having adverse event	Patients not taking drug not having adverse event
Hypomania	232.60	161.02	45	982	4343	46680692
Jaundice cholestatic	226.48	161.02	45	982	4984	46680051
Schizophrenia	202.58	161.02	45	982	8523	46676512
Hepatotoxicity	177.24	161.02	50	977	24959	46660076

FDA Adverse Event Reporting System (Male)

MedDRA adverse event term	Likelihood ratio	Likelihood ratio threshold	Patients taking drug having adverse event	Patients taking drug not having adverse event	Patients not taking drug having adverse event	Patients not taking drug not having adverse event
HIV infection	77.56	39.17	16	824	1652	29949986
Drug resistance	70.69	39.17	25	815	20108	29931530
Viral load increased	69.00	39.17	16	824	2838	29948800
Acquired immunodeficiency syndrome	62.10	39.17	11	829	503	29951135
Mycobacterial infection	54.33	39.17	12	828	1709	29949929
Opportunistic infection	51.88	39.17	11	829	1293	29950345
Dyschromatopsia	46.99	39.17	8	832	289	29951349
Viraemia	41.54	39.17	9	831	1170	29950468

Pharmacologic Action:

Source	Code	Description
ATC	J05AE09	ANTIINFECTIVES FOR SYSTEMIC USE ANTIVIRALS FOR SYSTEMIC USE DIRECT ACTING ANTIVIRALS Protease inhibitors
FDA MoA	N0000000246	HIV Protease Inhibitors
MeSH PA	D019380	Anti-HIV Agents
MeSH PA	D000890	Anti-Infective Agents
MeSH PA	D044966	Anti-Retroviral Agents
MeSH PA	D000998	Antiviral Agents
FDA EPC	N0000175889	Protease Inhibitor
CHEBI has role	CHEBI:35660	hiv protease inhibitors
CHEBI has role	CHEBI:36044	anti-virus drug

Drug Use (View source of the data)

Disease	Relation	SNOMED_ID	DOID
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

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation level	Dissociation constant	Type (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:

Target	Class	Pharos	UniProt	Action	Type	Activity value (-log[M])	Bioact source	MoA source
Multidrug resistance protein 1	Transporter	P08183	MDR1_HUMAN				WOMBAT-PK
Cathepsin D	Enzyme	P07339	CATD_HUMAN		Ki	4.82	CHEMBL
Pepsin A-5	Enzyme	P0DJD9	PEPA5_HUMAN		Ki	5.70	CHEMBL
Cathepsin E	Enzyme	P14091	CATE_HUMAN		Ki	5.05	CHEMBL
Pol polyprotein	Enzyme		Q72874_9HIV1	INHIBITOR	IC50	7.52	CHEMBL	CHEMBL
CAAX prenyl protease 1 homolog	Enzyme		FACE1_MOUSE		IC50	5.92	CHEMBL

External reference:

ID	Source
4024917	VUID
N0000171602	NUI
D08605	KEGG_DRUG
4024917	VANDF
C1612190	UMLSCUI
CHEBI:63628	CHEBI
TPV	PDB_CHEM_ID
CHEMBL222559	ChEMBL_ID
54682461	PUBCHEM_CID
C107201	MESH_SUPPLEMENTAL_RECORD_UI
7774	INN_ID
DB00932	DRUGBANK_ID
ZZT404XD09	UNII
190548	RXNORM
20182	MMSL
69882	MMSL
d05538	MMSL
010844	NDDF
418721002	SNOMEDCT_US
419409009	SNOMEDCT_US

Pharmaceutical products:

Product	Category	Ingredients	NDC	Form	Quantity	Route	Marketing	Label
Aptivus	HUMAN PRESCRIPTION DRUG LABEL	1	0597-0002	SOLUTION	100 mg	ORAL	NDA	32 sections
Aptivus	HUMAN PRESCRIPTION DRUG LABEL	1	0597-0003	CAPSULE, LIQUID FILLED	250 mg	ORAL	NDA	32 sections