INDINAVIR ANHYDROUS

US Previously Marketed

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C36H47N5O4
Molecular Weight	613.7895
Optical Activity	UNSPECIFIED
Defined Stereocenters	5 / 5
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CC(C)(C)NC(=O)[C@@H]1CN(CC2=CN=CC=C2)CCN1C[C@@H](O)C[C@@H](CC3=CC=CC=C3)C(=O)N[C@@H]4[C@H](O)CC5=C4C=CC=C5

InChI

InChIKey=CBVCZFGXHXORBI-PXQQMZJSSA-N

InChI=1S/C36H47N5O4/c1-36(2,3)39-35(45)31-24-40(22-26-12-9-15-37-21-26)16-17-41(31)23-29(42)19-28(18-25-10-5-4-6-11-25)34(44)38-33-30-14-8-7-13-27(30)20-32(33)43/h4-15,21,28-29,31-33,42-43H,16-20,22-24H2,1-3H3,(H,38,44)(H,39,45)/t28-,29+,31+,32-,33+/m1/s1

HIDE SMILES / InChI

Molecular Formula	C36H47N5O4
Molecular Weight	613.7895
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	5 / 5
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description
Sources: http://www.drugbank.ca/drugs/DB00224
Curator's Comment: Description was created based on several sources, including https://www.drugs.com/dosage/indinavir.html

Indinavir is an antiretroviral drug for the treatment of HIV infection. Indinavir 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. Indinavir 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.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
UDP-glucuronosyltransferase 1-1 15 Target ID: CHEMBL1287617 Sources: https://www.ncbi.nlm.nih.gov/pubmed/16118329	Inhibitor 8228	47.9 µM [Ki]
Human immunodeficiency virus type 1 protease 35 Target ID: CHEMBL243 Sources: http://www.drugbank.ca/drugs/DB00224	Inhibitor 8228	0.37 nM [Ki]
Leishmania amazonensis 8 Target ID: CHEMBL612877 Sources: https://www.ncbi.nlm.nih.gov/pubmed/22579524	Inhibitor 8228	100.0 µM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
HIV infection 21 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/020685s073lbl.pdf	Primary		Approved 8360	CRIXIVAN® Approved Use CRIXIVAN in combination with antiretroviral agents is indicated for the treatment of HIV infection. Launch Date 8.2555201E11

C_max

Value	Dose	Co-administered	Analyte	Population
12617 nM DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/020685s078lbl.pdf	800 mg 3 times / day steady-state, oral dose: 800 mg route of administration: Oral experiment type: STEADY-STATE co-administered:		INDINAVIR plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
17181 nM DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/020685s078lbl.pdf	500 mg/m² 3 times / day multiple, oral dose: 500 mg/m² route of administration: Oral experiment type: MULTIPLE co-administered:		INDINAVIR plasma	Homo sapiens population: UNHEALTHY age: CHILD sex: UNKNOWN food status: UNKNOWN

AUC

Value	Dose	Analyte	Population
9231 nM × h DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/020685s078lbl.pdf	800 mg 3 times / day multiple, oral dose: 800 mg route of administration: Oral experiment type: MULTIPLE co-administered:	INDINAVIR unknown	Homo sapiens population: PREGNANT age: ADULT sex: FEMALE food status: UNKNOWN
30691 nM × h DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/020685s078lbl.pdf	800 mg 3 times / day steady-state, oral dose: 800 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	INDINAVIR plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
38742 nM × h DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/020685s078lbl.pdf	500 mg/m² 3 times / day multiple, oral dose: 500 mg/m² route of administration: Oral experiment type: MULTIPLE co-administered:	INDINAVIR plasma	Homo sapiens population: UNHEALTHY age: CHILD sex: UNKNOWN food status: UNKNOWN

F_unbound

Value	Dose	Co-administered	Analyte	Population
40% DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/020685s078lbl.pdf	800 mg 3 times / day steady-state, oral dose: 800 mg route of administration: Oral experiment type: STEADY-STATE co-administered:		INDINAVIR plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

Doses

Dose	Population	Adverse events
2400 mg single, oral Overdose Dose: 2400 mg Route: oral Route: single Dose: 2400 mg Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/020685s073lbl.pdf Page: 20	unhealthy, adult n = 23 Health Status: unhealthy Condition: HIV-1 Age Group: adult Sex: unknown Population Size: 23 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/020685s073lbl.pdf Page: 20	Disc. AE: Renal disorders NEC, Gastrointestinal disorders NEC... AEs leading to discontinuation/dose reduction: Renal disorders NEC (23 patients) Gastrointestinal disorders NEC (23 patients) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/020685s073lbl.pdf Page: 20
1200 mg 2 times / day steady, oral Higher than recommended Dose: 1200 mg, 2 times / day Route: oral Route: steady Dose: 1200 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/10513637/ Page: 97	unhealthy, mean 42 years n = 5 Health Status: unhealthy Condition: HIV-1 Age Group: mean 42 years Sex: M+F Population Size: 5 Sources: https://pubmed.ncbi.nlm.nih.gov/10513637/ Page: 97	Other AEs: Renal disorders NEC... Other AEs: Renal disorders NEC (5 patients) Sources: https://pubmed.ncbi.nlm.nih.gov/10513637/ Page: 97

AEs

AE	Significance	Dose	Population
Gastrointestinal disorders NEC	23 patients Disc. AE	2400 mg single, oral Overdose Dose: 2400 mg Route: oral Route: single Dose: 2400 mg Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/020685s073lbl.pdf Page: 20	unhealthy, adult n = 23 Health Status: unhealthy Condition: HIV-1 Age Group: adult Sex: unknown Population Size: 23 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/020685s073lbl.pdf Page: 20
Renal disorders NEC	23 patients Disc. AE	2400 mg single, oral Overdose Dose: 2400 mg Route: oral Route: single Dose: 2400 mg Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/020685s073lbl.pdf Page: 20	unhealthy, adult n = 23 Health Status: unhealthy Condition: HIV-1 Age Group: adult Sex: unknown Population Size: 23 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/020685s073lbl.pdf Page: 20
Renal disorders NEC	5 patients	1200 mg 2 times / day steady, oral Higher than recommended Dose: 1200 mg, 2 times / day Route: oral Route: steady Dose: 1200 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/10513637/ Page: 97	unhealthy, mean 42 years n = 5 Health Status: unhealthy Condition: HIV-1 Age Group: mean 42 years Sex: M+F Population Size: 5 Sources: https://pubmed.ncbi.nlm.nih.gov/10513637/ Page: 97

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1709 inhibitor 1579	inhibitor 1752	inhibitor 1837 substrate 1193

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP1A2 1509 CYP2E1 876 CYP2B6 799	P-gp 1527

Drug as perpetrator

Target	Modality	Activity	Clinical evidence
CYP1A2 1673	inhibitor 3240 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/020685s078lbl.pdf#page=3 Page: 3.0	no
CYP2B6 985	inhibitor 3240 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/020685s078lbl.pdf#page=3 Page: 3.0	no
CYP2C9 1803	inhibitor 3240 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/020685s078lbl.pdf#page=3 Page: 3.0	no
CYP2E1 964	inhibitor 3240 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/020685s078lbl.pdf#page=3 Page: 3.0	no
CYP2D6 1875	inhibitor 3240 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/020685s078lbl.pdf#page=3 Page: 3.0	weak
CYP3A4 1909	inhibitor 3240 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/020685s078lbl.pdf#page=3 Page: 3.0	yes	yes (co-administration study) Comment: in the same study, clarithromycin AUC was increased by 53 ±36% and Cmax increased 22 ± 33% following coadministration with indinavir. Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/020685s078lbl.pdf#page=3 Page: 3.0

Drug as victim

Target	Modality	Activity	Clinical evidence
CYP2D6 1193	substrate 3326 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/pre96/020685Orig1s000rev.pdf#page=145 Page: 145.0	weak	no (co-administration study) Comment: Coadministration of quinidine sulfate (CYP2D6 inhibitor) did not significantly alter the pharmacokinetics of indinavir Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/pre96/020685Orig1s000rev.pdf#page=145 Page: 145.0
P-gp 1527	substrate 3326 Sources: https://pubmed.ncbi.nlm.nih.gov/9435299/ Page: -	yes
CYP3A4 1709	substrate 3326 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/020685s078lbl.pdf#page=2 Page: 2.0	yes	yes (co-administration study) Comment: Clarithromycin (500 mg q12h) increased the AUC of indinavir (800 mg q8h) by 29±42% and increased Cmax by 18±44%. Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/020685s078lbl.pdf#page=2 Page: 2.0

Sourcing

Vendor/Aggregator	ID	URL
3B Scientific (Wuhan) Corp	3B2-0207	http://www.3bsc.com/index/pro_info.php?id=19563
AA Blocks	AA001MH2	https://www.aablocks.com/goods/Goods/detail?id=AA001MH2
AHH Chemical co.,ltd	API-1193	http://www.ahhchemical.com/product/API-1193.html
AK Scientific, Inc. (AKSCI)	69104	http://www.aksci.com/item_detail.php?cat=69104
Aurora Fine Chemicals LLC	A13.111.810	http://online.aurorafinechemicals.com/info?ID=A13.111.810
AvaChem Scientific	2152B	http://www.avachem.com/productSearch.asp?2152B
BLD Pharm	BD134557	http://www.bldpharm.com/products/150378-17-9.html
BioSynth	J-008694	https://www.biosynth.com/en/products/all-products/products/J-008694.html
CSNpharm	CSN11198	https://www.csnpharm.com/products/indinavir.html
Chem Scene	CS-2930	http://www.chemscene.com/150378-17-9.html
ChemMol	30107683	http://www.chemmol.com/chemmol/30107683.html
ChemMol	99047026	http://www.chemmol.com/chemmol/99047026.html
Chemspace	CSSB00000053661	https://chem-space.com/CSSB00000053661
DC Chemicals	DC8906	http://www.dcchemicals.com/product_show-Indinavir.html
Glentham Life Sciences	GP8542	http://www.glentham.com/products/product/GP8542/
Hairui	HR130052	http://www.hairuichem.com/en/product/150378-17-9.html
Lab Network	LN00202000	https://labnetwork.com/frontend-app/p/#!/moleculedetails/LN00202000
Matrix Scientific	99281	https://www.matrixscientific.com/099281.html
MedChem Express	HY-B0689	https://www.medchemexpress.com/indinavir.html
OChem	7422	http://www.ocheminc.com/index.php?act=psearch&pid=378I179
Parchem	29155	http://www.parchem.com/chemical-supplier-distributor/Indinavir-019155.aspx
Smolecule	S530618	http://www.smolecule.com/products/s530618
THE BioTek	bt-271014	https://www.thebiotek.com/product/inhibitors/bt-271014
Yuhao Chemical	RT5885	http://www.chemyuhao.com/150378-17-9.html
eNovation Chemicals	D591373	https://www.enovationchem.com/ProductDetails.asp?ProductID=D591373
eNovation Chemicals	D674369	https://www.enovationchem.com/ProductDetails.asp?ProductID=D674369
iChemical	EBD41965	http://www.ichemical.com/chemicals/cas-150378-17-9

PubMed

Title	Date	PubMed
Non-active site changes elicit broad-based cross-resistance of the HIV-1 protease to inhibitors.	1999 Aug 20	10446127
In-vitro tipranavir susceptibility of HIV-1 isolates with reduced susceptibility to other protease inhibitors.	2000 Jan 7	10714580
Novel inhibitors of HIV protease: design, synthesis and biological evaluation of picomolar inhibitors containing cyclic P1/P2 scaffolds.	2000 Jun 5	10866371
Synthesis and anti-HIV activity of prodrugs derived from saquinavir and indinavir.	2000 Mar	10819434
In vitro activity of human immunodeficiency virus protease inhibitors against Pneumocystis carinii.	2000 May	10823762
PMS-601, a new platelet-activating factor receptor antagonist that inhibits human immunodeficiency virus replication and potentiates zidovudine activity in macrophages.	2000 Nov	11036039
The emerging roles of non-nucleoside reverse transcriptase inhibitors in antiretroviral therapy.	2001	11217868
Effects of grapefruit juice on pharmacokinetic exposure to indinavir in HIV-positive subjects.	2001 Apr	11304900
Intracellular concentration of the HIV protease inhibitors indinavir and saquinavir in human endothelial cells.	2001 Apr	11266428
A phase II trial of dual protease inhibitor therapy: amprenavir in combination with indinavir, nelfinavir, or saquinavir.	2001 Apr 15	11391165
[Acute porphyria and indinavir].	2001 Feb	11275609
Therapy with efavirenz plus indinavir in patients with extensive prior nucleoside reverse-transcriptase inhibitor experience: a randomized, double-blind, placebo-controlled trial.	2001 Feb 1	11133370
The absence of hyperbilirubinaemia is highly predictive of treatment failure in advanced HIV-infected patients treated with indinavir.	2001 Jan	11177479
[Vertical trasmission of human immunodeficiency virus (HIV) and other sexually transmitted infections (STI)].	2001 Jun	11395690
The HIV protease inhibitor indinavir decreases insulin- and contraction-stimulated glucose transport in skeletal muscle.	2001 Jun	11375341
The HIV protease inhibitor indinavir impairs sterol regulatory element-binding protein-1 intranuclear localization, inhibits preadipocyte differentiation, and induces insulin resistance.	2001 Jun	11375339
Alterations in T cell phenotype and human immunodeficiency virus type 1-specific cytotoxicity after potent antiretroviral therapy.	2001 Mar 1	11181148
Indinavir, nevirapine, stavudine, and lamivudine for human immunodeficiency virus-infected, amprenavir-experienced subjects: AIDS Clinical Trials Group protocol 373.	2001 Mar 1	11181147
Residual human immunodeficiency virus type 1 infection in lymphoid tissue during highly active antiretroviral therapy: quantitation and virus characterization.	2001 May 1	11375053
Treatment of primary human immunodeficiency virus type 1 infection with potent antiretroviral therapy reduces frequency of rapid progression to AIDS.	2001 May 15	11319682
Is indinavir crystalluria an indicator for indinavir stone formation?	2001 May 25	11400000
Low incidence of genotypic and phenotypic resistance in paediatric HIV-infected patients on long-term first-line antiretroviral triple therapy.	2001 May 25	11399999
'Do HIV-infected injecting drug users over-report adherence to highly active antiretroviral therapy?' A comparison between patients' self-reports and serum protease inhibitor concentrations in the French Manif 2000 cohort study.	2001 May 25	11399998
Clinical outcome among HIV-infected patients starting saquinavir hard gel compared to ritonavir or indinavir.	2001 May 25	11399982
Metabolic effects of indinavir in healthy HIV-seronegative men.	2001 May 4	11399973
[Effective in HIV: dual combination with indinavir and ritonavir].	2001 May 4	11381644

Patents

Sample Use Guides

In Vivo Use Guide

Usual Adult Dose for HIV Infection 800 mg orally every 8 hours or indinavir 800 mg plus ritonavir 100 to 200 mg orally every 12 hours

Route of Administration: Oral

In Vitro Use Guide

Indinavir (10 nM) gave 14% inhibition of HIV replication alone and 81% in combination with P-gp/MRP inhibitors.

Substance Class	Chemical Created by `admin` on `Wed Jul 05 23:31:35 UTC 2023` Edited by `admin` on `Wed Jul 05 23:31:35 UTC 2023`
Record UNII	9MG78X43ZT
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

INDINAVIR ANHYDROUS

Common Name

English

(.ALPHA.R,.GAMMA.S,2S)-.ALPHA.-BENZYL-2-(TERT-BUTYLCARBAMOYL)-.GAMMA.-HYDROXY-N-((1S,2R)-2-HYDROXY-1-INDANYL)-4-(3-PYRIDYLMETHYL)-1-PIPERAZINEVALERAMIDE

Common Name

English

indinavir [INN]

Common Name

English

D-ERYTHRO-PENTONAMIDE, 2,3,5-TRIDEOXY-N-(2,3-DIHYDRO-2-HYDROXY-1H-INDEN-1-YL)-5-(2-(((1,1-DIMETHYLETHYL)AMINO)CARBONYL)-4-(3-PYRIDINYLMETHYL)-1-PIPERAZINYL)-2-(PHENYLMETHYL)-, (1(1S,2R),5(S))-

Common Name

English

Indinavir [WHO-DD]

Common Name

English

INDINAVIR [MI]

Common Name

English

Classification Tree Code System Code

NDF-RT

N0000175889