Atazanavir

Identification

Summary

Atazanavir is an antiviral protease inhibitor used in combination with other antiretrovirals for the treatment of HIV.

Brand Names
Evotaz, Reyataz
Generic Name
Atazanavir
DrugBank Accession Number
DB01072
Background

Atazanavir (formerly known as BMS-232632) is an antiretroviral drug of the protease inhibitor (PI) class. Like other antiretrovirals, it is used to treat infection of human immunodeficiency virus (HIV). Atazanavir is distinguished from other PIs in that it can be given once daily (rather than requiring multiple doses per day) and has lesser effects on the patient's lipid profile (the amounts of cholesterol and other fatty substances in the blood). Like other protease inhibitors, it is used only in combination with other HIV medications. The U.S. Food and Drug Administration (FDA) approved atazanavir on June 20, 2003.

Type
Small Molecule
Groups
Approved, Investigational
Structure
Weight
Average: 704.8555
Monoisotopic: 704.389748048
Chemical Formula
C38H52N6O7
Synonyms
  • Atazanavir
  • Atazanavirum
  • ATZ
External IDs
  • BMS-232632
  • CGP-73547

Pharmacology

Indication

Atazanavir is indicated in combination with other antiretroviral agents for the treatment of HIV-1 infection in adults and pediatric patients 3 months of age and older weighing at least 5kg.9 Atazanavir is also indicated in combination with cobicistat and other antiretrovirals for the treatment of HIV-1 infection in adults and pediatric patients weighing at least 35kg.8

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Associated Conditions
Indication TypeIndicationCombined Product DetailsApproval LevelAge GroupPatient CharacteristicsDose Form
Adjunct therapy in treatment ofHuman immunodeficiency virus type 1 (hiv-1) infection•••••••••••••••••••••••• ••••••
Adjunct therapy in treatment ofHuman immunodeficiency virus type 1 (hiv-1) infection••••••••••••••••••••••••••• ••••••••••• ••••••
Used as adjunct in combination to treatHuman immunodeficiency virus type 1 (hiv-1) infectionCombination Product in combination with: Cobicistat (DB09065)••••••••••••••••••••••• •••••• ••••••••••••••• •• ••••• •• ••••••••
Contraindications & Blackbox Warnings
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Pharmacodynamics

Atazanavir (ATV) is an azapeptide HIV-1 protease inhibitor (PI) with activity against Human Immunodeficiency Virus Type 1 (HIV-1). 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. Atazanavir 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. Atazanivir is pharmacologically related but structurally different from other protease inhibitors and other currently available antiretrovirals.6

Atazanavir exhibits anti-HIV-1 activity with a mean 50% effective concentration (EC50) in the absence of human serum of 2 to 5 nM against a variety of laboratory and clinical HIV-1 isolates grown in peripheral blood mononuclear cells, macrophages, CEM-SS cells, and MT-2 cells.10

Atazanavir has activity against HIV-1 Group M subtype viruses A, B, C, D, AE, AG, F, G, and J isolates in cell culture. Atazanavir has variable activity against HIV-2 isolates (1.9-32 nM), with EC50 values above the EC50 values of failure isolates. Two-drug combination antiviral activity studies with atazanavir showed no antagonism in cell culture with PIs (amprenavir, indinavir, lopinavir, nelfinavir, ritonavir, and saquinavir), NNRTIs (delavirdine, efavirenz, and nevirapine), NRTIs (abacavir, didanosine, emtricitabine, lamivudine, stavudine, tenofovir DF, and zidovudine), the HIV-1 fusion inhibitor enfuvirtide, and two compounds used in the treatment of viral hepatitis, adefovir and ribavirin, without enhanced cytotoxicity.10

HIV-1 isolates with a decreased susceptibility to atazanavir have been selected in cell culture and obtained from patients treated with atazanavir or atazanavir with ritonavir. HIV-1 isolates with 93- to 183-fold reduced susceptibility to atazanavir from three different viral strains were selected in cell culture for 5 months. The substitutions in these HIV-1 viruses that contributed to atazanavir resistance include I50L, N88S, I84V, A71V, and M46I. Changes were also observed at the protease cleavage sites following drug selection. Recombinant viruses containing the I50L substitution without other major PI substitutions were growth impaired and displayed increased susceptibility in cell culture to other PIs (amprenavir, indinavir, lopinavir, nelfinavir, ritonavir, and saquinavir). The I50L and I50V substitutions yielded selective resistance to atazanavir and amprenavir, respectively, and did not appear to be cross-resistant.10

Concentration- and dose-dependent prolongation of the PR interval in the electrocardiogram has been observed in healthy subjects receiving atazanavir. In placebo-controlled Study AI424-076, the mean (±SD) maximum change in PR interval from the predose value was 24 (±15) msec following oral dosing with 400 mg of atazanavir (n=65) compared to 13 (±11) msec following dosing with placebo (n=67). The PR interval prolongations in this study were asymptomatic. There is limited information on the potential for a pharmacodynamic interaction in humans between atazanavir and other drugs that prolong the PR interval of the electrocardiogram.

Electrocardiographic effects of atazanavir were determined in a clinical pharmacology study of 72 healthy subjects. Oral doses of 400 mg (maximum recommended dosage) and 800 mg (twice the maximum recommended dosage) were compared with placebo; there was no concentration-dependent effect of atazanavir on the QTc interval (using Fridericia’s correction). In 1793 subjects with HIV-1 infection, receiving antiretroviral regimens, QTc prolongation was comparable in the atazanavir and comparator regimens. No atazanavir-treated healthy subject or subject with HIV-1 infection in clinical trials had a QTc interval >500 msec

Mechanism of action

Atazanavir selectively inhibits the virus-specific processing of viral Gag and Gag-Pol polyproteins in HIV-1 infected cells by binding to the active site of HIV-1 protease, thus preventing the formation of mature virions. Atazanavir is not active against HIV-2.10

TargetActionsOrganism
AHuman immunodeficiency virus type 1 protease
inhibitor
Human immunodeficiency virus 1
Absorption

Atazanavir is rapidly absorbed with a Tmax of approximately 2.5 hours. Atazanavir demonstrates nonlinear pharmacokinetics with greater than dose-proportional increases in AUC and Cmax values over the dose range of 200 to 800 mg once daily. A steady state is achieved between Days 4 and 8, with an accumulation of approximately 2.3-fold.10

Administration of atazanavir with food enhances bioavailability and reduces pharmacokinetic variability. Administration of a single 400-mg dose of atazanavir with a light meal (357 kcal, 8.2 g fat, 10.6 g protein) resulted in a 70% increase in AUC and 57% increase in Cmax relative to the fasting state. Administration of a single 400-mg dose of atazanavir with a high-fat meal (721 kcal, 37.3 g fat, 29.4 g protein) resulted in a mean increase in AUC of 35% with no change in Cmax relative to the fasting state. Administration of atazanavir with either a light or high-fat meal decreased the coefficient of variation of AUC and Cmax by approximately one-half compared to the fasting state.10

Coadministration of a single 300-mg dose of atazanavir and a 100-mg dose of ritonavir with a light meal (336 kcal, 5.1 g fat, 9.3 g protein) resulted in a 33% increase in the AUC and a 40% increase in both the Cmax and the 24-hour concentration of atazanavir relative to the fasting state. Coadministration with a high-fat meal (951 kcal, 54.7 g fat, 35.9 g protein) did not affect the AUC of atazanavir relative to fasting conditions and the Cmax was within 11% of fasting values. The 24-hour concentration following a high-fat meal was increased by approximately 33% due to delayed absorption; the median Tmax increased from 2.0 to 5.0 hours. Coadministration of atazanavir with ritonavir with either a light or a high-fat meal decreased the coefficient of variation of AUC and Cmax by approximately 25% compared to the fasting state.10

Volume of distribution

In patients with HIV infection, the volume of distribution of atazanavir was estimated to be 88.3 L.7

Protein binding

Atazanavir is 86% bound to human serum proteins and protein binding is independent of concentration. Atazanavir binds to both alpha-1-acid glycoprotein (AAG) and albumin to a similar extent (89% and 86%, respectively).10

Metabolism

Atazanavir is extensively metabolized in humans. The major biotransformation pathways of atazanavir in humans consisted of monooxygenation and dioxygenation. Other minor biotransformation pathways for atazanavir or its metabolites consisted of glucuronidation, N-dealkylation, hydrolysis, and oxygenation with dehydrogenation. Two minor metabolites of atazanavir in plasma have been characterized. Neither metabolite demonstrated in vitro antiviral activity. In vitro studies using human liver microsomes suggested that atazanavir is metabolized by CYP3A.10

Route of elimination

Following a single 400-mg dose of 14C-atazanavir, 79% and 13% of the total radioactivity was recovered in the feces and urine, respectively. Unchanged drugs accounted for approximately 20% and 7% of the administered dose in the feces and urine, respectively.10

Half-life

The mean elimination half-life of atazanavir in healthy subjects (n=214) and adult subjects with HIV-1 infection (n=13) was approximately 7 hours at steady state following a dose of 400 mg daily with a light meal. Elimination half-life in hepatically impaired is 12.1 hours (following a single 400 mg dose).10

Clearance

In patients with HIV infection, the clearance of atazanavir was estimated to be 12.9 L/hr.7

Adverse Effects
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Toxicity

Not Available

Pathways
Not Available
Pharmacogenomic Effects/ADRs
Interacting Gene/EnzymeAllele nameGenotype(s)Defining Change(s)Type(s)DescriptionDetails
UDP-glucuronosyltransferase 1-1UGT1A1*28(TA;TA)TA pair insertionADR Directly StudiedThe presence of this genotype in UGT1A1 may indicate an increased risk of hyperbilirubinemia from atazanavir treatment.Details
UDP-glucuronosyltransferase 1-1UGT1A1*37(TA;TA)TA pair insertionADR Directly StudiedThe presence of this genotype in UGT1A1 may indicate an increased risk of hyperbilirubinemia from atazanavir treatment.Details
UDP-glucuronosyltransferase 1-1UGT1A1*80(T;T)G > A, homozygousADR Directly StudiedThe presence of this genotype in UGT1A1 may indicate an increased risk of hyperbilirubinemia from atazanavir treatment.Details

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
1,2-BenzodiazepineThe metabolism of 1,2-Benzodiazepine can be decreased when combined with Atazanavir.
AbacavirThe serum concentration of Abacavir can be decreased when it is combined with Atazanavir.
AbametapirThe serum concentration of Atazanavir can be increased when it is combined with Abametapir.
AbataceptThe metabolism of Atazanavir can be increased when combined with Abatacept.
AbemaciclibThe metabolism of Abemaciclib can be decreased when combined with Atazanavir.
Food Interactions
  • Take with food. Food increases product absorption and reduces pharmacokinetic variability.

Products

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Product Ingredients
IngredientUNIICASInChI Key
Atazanavir sulfate4MT4VIE29P229975-97-7DQSGVVGOPRWTKI-QVFAWCHISA-N
International/Other Brands
Latazanavir / Zrivada
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
Atazanavir KrkaCapsule300 mgOralKrka D D., Novo Mesto2020-12-16Not applicableEU flag
Atazanavir KrkaCapsule150 mgOralKrka D D., Novo Mesto2020-12-16Not applicableEU flag
Atazanavir KrkaCapsule300 mgOralKrka D D., Novo Mesto2020-12-16Not applicableEU flag
Atazanavir KrkaCapsule200 mgOralKrka D D., Novo Mesto2020-12-16Not applicableEU flag
Atazanavir MylanCapsule200 mgOralMylan Pharmaceuticals Limited2021-01-12Not applicableEU flag
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
Apo-atazanavirCapsule300 mgOralApotex CorporationNot applicableNot applicableCanada flag
Apo-atazanavirCapsule200 mgOralApotex CorporationNot applicableNot applicableCanada flag
Apo-atazanavirCapsule150 mgOralApotex CorporationNot applicableNot applicableCanada flag
AtazanavirCapsule300 mg/1OralAmneal Pharmaceuticals NY LLC2020-06-03Not applicableUS flag
AtazanavirCapsule, gelatin coated300 mg/1OralCipla USA Inc.2018-09-14Not applicableUS flag
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing EndRegionImage
ANCEF ® RAtazanavir sulfate (300 mg) + Ritonavir (100 mg)Tablet, coatedOralLABORATORIOS LEGRAND S.A.2018-03-13Not applicableColombia flag
EvotazAtazanavir sulfate (300 mg) + Cobicistat (150 mg)Tablet, film coatedOralBristol Myers Squibb Pharma Eeig2020-12-22Not applicableEU flag
EVOTAZAtazanavir (300 MG) + Cobicistat (150 MG)Tablet, film coatedOralBristol Myers Squibb Pharma Eeig2015-10-14Not applicableItaly flag
EvotazAtazanavir sulfate (300 mg/1) + Cobicistat (150 mg/1)TabletOralE.R. Squibb & Sons, L.L.C.2015-01-29Not applicableUS flag
EvotazAtazanavir sulfate (300 mg) + Cobicistat (150 mg)TabletOralBristol Myers Squibb2016-02-112017-09-22Canada flag

Categories

ATC Codes
J05AE08 — AtazanavirJ05AR15 — Atazanavir and cobicistatJ05AR23 — Atazanavir and ritonavir
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as valine and derivatives. These are compounds containing valine or a derivative thereof resulting from reaction of valine at the amino group or the carboxy group, or from the replacement of any hydrogen of glycine by a heteroatom.
Kingdom
Organic compounds
Super Class
Organic acids and derivatives
Class
Carboxylic acids and derivatives
Sub Class
Amino acids, peptides, and analogues
Direct Parent
Valine and derivatives
Alternative Parents
Alpha amino acid amides / Phenylpyridines / Phenylbutylamines / Amphetamines and derivatives / N-acyl amines / Heteroaromatic compounds / Methylcarbamates / Secondary carboxylic acid amides / Secondary alcohols / Carboxylic acid hydrazides
show 7 more
Substituents
2-phenylpyridine / Alcohol / Alpha-amino acid amide / Amphetamine or derivatives / Aromatic heteromonocyclic compound / Azacycle / Benzenoid / Carbamic acid ester / Carbonic acid derivative / Carbonyl group
show 21 more
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
carbohydrazide (CHEBI:37924)
Affected organisms
  • Human Immunodeficiency Virus

Chemical Identifiers

UNII
QZU4H47A3S
CAS number
198904-31-3
InChI Key
AXRYRYVKAWYZBR-GASGPIRDSA-N
InChI
InChI=1S/C38H52N6O7/c1-37(2,3)31(41-35(48)50-7)33(46)40-29(22-25-14-10-9-11-15-25)30(45)24-44(43-34(47)32(38(4,5)6)42-36(49)51-8)23-26-17-19-27(20-18-26)28-16-12-13-21-39-28/h9-21,29-32,45H,22-24H2,1-8H3,(H,40,46)(H,41,48)(H,42,49)(H,43,47)/t29-,30-,31+,32+/m0/s1
IUPAC Name
methyl N-[(1S)-1-{N'-[(2S,3S)-2-hydroxy-3-[(2S)-2-[(methoxycarbonyl)amino]-3,3-dimethylbutanamido]-4-phenylbutyl]-N'-{[4-(pyridin-2-yl)phenyl]methyl}hydrazinecarbonyl}-2,2-dimethylpropyl]carbamate
SMILES
COC(=O)N[C@H](C(=O)N[C@@H](CC1=CC=CC=C1)[C@@H](O)CN(CC1=CC=C(C=C1)C1=CC=CC=N1)NC(=O)[C@@H](NC(=O)OC)C(C)(C)C)C(C)(C)C

References

Synthesis Reference
US5849911
General References
  1. Croom KF, Dhillon S, Keam SJ: Atazanavir: a review of its use in the management of HIV-1 infection. Drugs. 2009 May 29;69(8):1107-40. doi: 10.2165/00003495-200969080-00009. [Article]
  2. von Hentig N: Atazanavir/ritonavir: a review of its use in HIV therapy. Drugs Today (Barc). 2008 Feb;44(2):103-32. doi: 10.1358/dot.2008.44.2.1137107. [Article]
  3. Swainston Harrison T, Scott LJ: Atazanavir: a review of its use in the management of HIV infection. Drugs. 2005;65(16):2309-36. [Article]
  4. Le Tiec C, Barrail A, Goujard C, Taburet AM: Clinical pharmacokinetics and summary of efficacy and tolerability of atazanavir. Clin Pharmacokinet. 2005;44(10):1035-50. [Article]
  5. Lopez-Cortes LF: [Pharmacology, pharmacokinetic features and interactions of atazanavir]. Enferm Infecc Microbiol Clin. 2008 Dec;26 Suppl 17:2-8. doi: 10.1016/S0213-005X(08)76613-8. [Article]
  6. Busti AJ, Hall RG, Margolis DM: Atazanavir for the treatment of human immunodeficiency virus infection. Pharmacotherapy. 2004 Dec;24(12):1732-47. [Article]
  7. Colombo S, Buclin T, Cavassini M, Decosterd LA, Telenti A, Biollaz J, Csajka C: Population pharmacokinetics of atazanavir in patients with human immunodeficiency virus infection. Antimicrob Agents Chemother. 2006 Nov;50(11):3801-8. doi: 10.1128/AAC.00098-06. Epub 2006 Aug 28. [Article]
  8. FDA Approved Drug Products: Evotaz (atazanavir and cobicistat) oral tablets [Link]
  9. FDA Approved Drug Products: Reyataz (atazanavir) for oral use [Link]
  10. FDA Approved Drug Products: REYATAZ (atazanavir) capsules/oral powder, for oral use [Link]
Human Metabolome Database
HMDB0015205
KEGG Drug
D07471
PubChem Compound
148192
PubChem Substance
46508504
ChemSpider
130642
BindingDB
13934
RxNav
343047
ChEBI
37924
ChEMBL
CHEMBL1163
ZINC
ZINC000003941496
Therapeutic Targets Database
DNC000332
PharmGKB
PA10251
PDBe Ligand
DR7
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
PDRhealth
PDRhealth Drug Page
Wikipedia
Atazanavir
PDB Entries
2aqu / 2fxd / 2fxe / 2o4k / 3ekw / 3eky / 3el1 / 3el9 / 3oxx
FDA label
Download (412 KB)

Clinical Trials

Clinical Trials
Clinical Trial & Rare Diseases Add-on Data Package
Explore 4,000+ rare diseases, orphan drugs & condition pairs, clinical trial why stopped data, & more. Preview package
PhaseStatusPurposeConditionsCountStart DateWhy Stopped100+ additional columns
4CompletedNot AvailableHealthy Volunteers (HV)1somestatusstop reasonjust information to hide
4CompletedNot AvailableHuman Immunodeficiency Virus (HIV) Infections2somestatusstop reasonjust information to hide
4CompletedNot AvailableHuman Immunodeficiency Virus (HIV) Infections / Proteinuria1somestatusstop reasonjust information to hide
4CompletedBasic ScienceDrug Drug Interaction (DDI)1somestatusstop reasonjust information to hide
4CompletedOtherHuman Immunodeficiency Virus (HIV) Infections1somestatusstop reasonjust information to hide

Pharmacoeconomics

Manufacturers
Not Available
Packagers
  • A-S Medication Solutions LLC
  • Bristol-Myers Squibb Co.
  • E.R. Squibb and Sons LLC
  • Kaiser Foundation Hospital
  • Lake Erie Medical and Surgical Supply
  • PCA LLC
  • Physicians Total Care Inc.
  • Remedy Repack
Dosage Forms
FormRouteStrength
Tablet, coatedOral
CapsuleOral300.00 mg
Capsule, coatedOral200 mg
Capsule, coatedOral300 mg
CapsuleOral100 mg/1
CapsuleOral150 mg/1
CapsuleOral200 mg/1
CapsuleOral300 mg/1
PowderNot applicable25 kg/25kg
CapsuleOral
CapsuleOral200.000 mg
CapsuleOral341.720 mg
CapsuleOral341.740 mg
TabletOral
Tablet, film coatedOral
CapsuleOral100 mg
Capsule, gelatin coatedOral100 mg/1
Capsule, gelatin coatedOral150 mg/1
Capsule, gelatin coatedOral200 mg/1
Capsule, gelatin coatedOral300 mg/1
PowderOral50 mg/1
PowderOral50 MG/1.5G
PowderOral50 MG
CapsuleOral150 mg
CapsuleOral200 mg
CapsuleOral300 mg
Capsule, coatedOral150 mg
CapsuleOral341.700 mg
PowderOral50 mg/1sachet
Prices
Unit descriptionCostUnit
Reyataz 300 mg capsule36.63USD capsule
Reyataz 150 mg capsule18.49USD capsule
Reyataz 200 mg capsule18.49USD capsule
Reyataz 100 mg capsule18.12USD capsule
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)Region
CA2250840No2006-07-042017-04-14Canada flag
CA2317736No2004-11-022018-12-22Canada flag
US5849911Yes1998-12-152017-12-20US flag
US6087383Yes2000-07-112019-06-21US flag
US8148374Yes2012-04-032030-03-03US flag
US10039718Yes2018-08-072033-04-06US flag

Properties

State
Solid
Experimental Properties
PropertyValueSource
water solubilityFree base slightly soluble (4-5 mg/mL)Not Available
logP4.5https://www.nature.com/articles/s41467-019-12141-5
Predicted Properties
PropertyValueSource
Water Solubility0.00327 mg/mLALOGPS
logP4.08ALOGPS
logP4.54Chemaxon
logS-5.3ALOGPS
pKa (Strongest Acidic)11.92Chemaxon
pKa (Strongest Basic)4.42Chemaxon
Physiological Charge0Chemaxon
Hydrogen Acceptor Count7Chemaxon
Hydrogen Donor Count5Chemaxon
Polar Surface Area171.22 Å2Chemaxon
Rotatable Bond Count18Chemaxon
Refractivity191.8 m3·mol-1Chemaxon
Polarizability76.73 Å3Chemaxon
Number of Rings3Chemaxon
Bioavailability0Chemaxon
Rule of FiveNoChemaxon
Ghose FilterNoChemaxon
Veber's RuleNoChemaxon
MDDR-like RuleYesChemaxon
Predicted ADMET Features
PropertyValueProbability
Human Intestinal Absorption+0.7997
Blood Brain Barrier-0.9409
Caco-2 permeable-0.7017
P-glycoprotein substrateSubstrate0.832
P-glycoprotein inhibitor IInhibitor0.81
P-glycoprotein inhibitor IINon-inhibitor0.844
Renal organic cation transporterNon-inhibitor0.924
CYP450 2C9 substrateNon-substrate0.7898
CYP450 2D6 substrateNon-substrate0.9116
CYP450 3A4 substrateSubstrate0.6463
CYP450 1A2 substrateNon-inhibitor0.7553
CYP450 2C9 inhibitorNon-inhibitor0.7041
CYP450 2D6 inhibitorNon-inhibitor0.848
CYP450 2C19 inhibitorNon-inhibitor0.5948
CYP450 3A4 inhibitorNon-inhibitor0.8425
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.7718
Ames testNon AMES toxic0.6714
CarcinogenicityNon-carcinogens0.7261
BiodegradationNot ready biodegradable1.0
Rat acute toxicity2.7082 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9766
hERG inhibition (predictor II)Inhibitor0.6538
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSsplash10-03xs-5617198000-83a5e695710baf354772
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSsplash10-0fee-0100029000-9e1e7e3188f522f4191e
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSsplash10-001i-1502094000-624f29d710755c9cd5ae
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSsplash10-001i-1001090000-d1adb6fc0f17d1ecadd5
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSsplash10-0671-2500495000-3378de4b52d8689ec565
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSsplash10-0kg9-0004942000-f04c45bb06332e2e512a
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSsplash10-0cei-9110487000-92d6beb23f0e594e7752
Chromatographic Properties
Collision Cross Sections (CCS)
AdductCCS Value (Å2)Source typeSource
[M-H]-252.5268718
predicted
DarkChem Lite v0.1.0
[M-H]-281.7681718
predicted
DarkChem Lite v0.1.0
[M-H]-266.5693718
predicted
DarkChem Lite v0.1.0
[M-H]-253.05579
predicted
DeepCCS 1.0 (2019)
[M+H]+254.1485718
predicted
DarkChem Lite v0.1.0
[M+H]+282.4041718
predicted
DarkChem Lite v0.1.0
[M+H]+265.7457718
predicted
DarkChem Lite v0.1.0
[M+H]+254.84868
predicted
DeepCCS 1.0 (2019)
[M+Na]+273.6958718
predicted
DarkChem Lite v0.1.0
[M+Na]+281.6401718
predicted
DarkChem Lite v0.1.0
[M+Na]+261.05154
predicted
DeepCCS 1.0 (2019)

Targets

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Kind
Protein
Organism
Human immunodeficiency virus 1
Pharmacological action
Yes
Actions
Inhibitor
General Function
Aspartic-type endopeptidase activity
Specific Function
Not Available
Gene Name
pol
Uniprot ID
Q72874
Uniprot Name
Pol polyprotein
Molecular Weight
10778.7 Da
References
  1. Dierynck I, De Wit M, Gustin E, Keuleers I, Vandersmissen J, Hallenberger S, Hertogs K: Binding kinetics of darunavir to human immunodeficiency virus type 1 protease explain the potent antiviral activity and high genetic barrier. J Virol. 2007 Dec;81(24):13845-51. Epub 2007 Oct 10. [Article]
  2. Dandache S, Sevigny G, Yelle J, Stranix BR, Parkin N, Schapiro JM, Wainberg MA, Wu JJ: In vitro antiviral activity and cross-resistance profile of PL-100, a novel protease inhibitor of human immunodeficiency virus type 1. Antimicrob Agents Chemother. 2007 Nov;51(11):4036-43. Epub 2007 Jul 16. [Article]
  3. Wood R: Atazanavir: its role in HIV treatment. Expert Rev Anti Infect Ther. 2008 Dec;6(6):785-96. doi: 10.1586/14787210.6.6.785. [Article]
  4. Le Tiec C, Barrail A, Goujard C, Taburet AM: Clinical pharmacokinetics and summary of efficacy and tolerability of atazanavir. Clin Pharmacokinet. 2005;44(10):1035-50. [Article]
  5. Pyrko P, Kardosh A, Wang W, Xiong W, Schonthal AH, Chen TC: HIV-1 protease inhibitors nelfinavir and atazanavir induce malignant glioma death by triggering endoplasmic reticulum stress. Cancer Res. 2007 Nov 15;67(22):10920-8. [Article]
  6. Menendez-Arias L, Tozser J: HIV-1 protease inhibitors: effects on HIV-2 replication and resistance. Trends Pharmacol Sci. 2008 Jan;29(1):42-9. Epub 2007 Dec 4. [Article]
  7. Lopez-Cortes LF: [Pharmacology, pharmacokinetic features and interactions of atazanavir]. Enferm Infecc Microbiol Clin. 2008 Dec;26 Suppl 17:2-8. doi: 10.1016/S0213-005X(08)76613-8. [Article]
  8. Busti AJ, Hall RG, Margolis DM: Atazanavir for the treatment of human immunodeficiency virus infection. Pharmacotherapy. 2004 Dec;24(12):1732-47. [Article]
  9. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]
  10. FDA Approved Drug Products: REYATAZ (atazanavir) capsules/oral powder, for oral use [Link]

Enzymes

Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
Inhibitor
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. Le Tiec C, Barrail A, Goujard C, Taburet AM: Clinical pharmacokinetics and summary of efficacy and tolerability of atazanavir. Clin Pharmacokinet. 2005;44(10):1035-50. [Article]
  2. Busti AJ, Hall RG, Margolis DM: Atazanavir for the treatment of human immunodeficiency virus infection. Pharmacotherapy. 2004 Dec;24(12):1732-47. [Article]
  3. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. [Article]
  4. Atazanavir FDA Label [Link]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP2C9
Uniprot ID
P11712
Uniprot Name
Cytochrome P450 2C9
Molecular Weight
55627.365 Da
References
  1. Busti AJ, Hall RG, Margolis DM: Atazanavir for the treatment of human immunodeficiency virus infection. Pharmacotherapy. 2004 Dec;24(12):1732-47. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Inhibitor
General Function
Steroid binding
Specific Function
UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This isoform glucuronidates bilirubin IX-alpha to form both the...
Gene Name
UGT1A1
Uniprot ID
P22309
Uniprot Name
UDP-glucuronosyltransferase 1-1
Molecular Weight
59590.91 Da
References
  1. Marques SC, Ikediobi ON: The clinical application of UGT1A1 pharmacogenetic testing: gene-environment interactions. Hum Genomics. 2010 Apr;4(4):238-49. doi: 10.1186/1479-7364-4-4-238. [Article]
  2. Burger DM, Huisman A, Van Ewijk N, Neisingh H, Van Uden P, Rongen GA, Koopmans P, Bertz RJ: The effect of atazanavir and atazanavir/ritonavir on UDP-glucuronosyltransferase using lamotrigine as a phenotypic probe. Clin Pharmacol Ther. 2008 Dec;84(6):698-703. doi: 10.1038/clpt.2008.106. Epub 2008 Jun 4. [Article]
  3. Atazanavir FDA Label [Link]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP2C8
Uniprot ID
P10632
Uniprot Name
Cytochrome P450 2C8
Molecular Weight
55824.275 Da
References
  1. Atazanavir FDA Label [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP1A2
Uniprot ID
P05177
Uniprot Name
Cytochrome P450 1A2
Molecular Weight
58293.76 Da
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Oxygen binding
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP3A5
Uniprot ID
P20815
Uniprot Name
Cytochrome P450 3A5
Molecular Weight
57108.065 Da
References
  1. FDA Approved Drug Products: REYATAZ (atazanavir) capsules/oral powder, for oral use [Link]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Inhibitor
General Function
Oxygen binding
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP3A7
Uniprot ID
P24462
Uniprot Name
Cytochrome P450 3A7
Molecular Weight
57525.03 Da
References
  1. FDA Approved Drug Products: REYATAZ (atazanavir) capsules/oral powder, for oral use [Link]

Carriers

Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Binder
General Function
Toxic substance binding
Specific Function
Serum albumin, the main protein of plasma, has a good binding capacity for water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs. Its main function is the regulation of the colloid...
Gene Name
ALB
Uniprot ID
P02768
Uniprot Name
Serum albumin
Molecular Weight
69365.94 Da
References
  1. Bocedi A, Notaril S, Narciso P, Bolli A, Fasano M, Ascenzi P: Binding of anti-HIV drugs to human serum albumin. IUBMB Life. 2004 Oct;56(10):609-14. [Article]
  2. Bocedi A, Notari S, Menegatti E, Fanali G, Fasano M, Ascenzi P: Allosteric modulation of anti-HIV drug and ferric heme binding to human serum albumin. FEBS J. 2005 Dec;272(24):6287-96. [Article]
  3. FDA Approved Drug Products: REYATAZ (atazanavir) capsules/oral powder, for oral use [Link]
Kind
Protein group
Organism
Humans
Pharmacological action
No
Actions
Binder
General Function
Not Available
Specific Function
Functions as transport protein in the blood stream. Binds various ligands in the interior of its beta-barrel domain. Also binds synthetic drugs and influences their distribution and availability in...

Components:
References
  1. FDA Approved Drug Products: REYATAZ (atazanavir) capsules/oral powder, for oral use [Link]

Transporters

Details
1. P-glycoprotein 1
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
Inducer
General Function
Xenobiotic-transporting atpase activity
Specific Function
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
Gene Name
ABCB1
Uniprot ID
P08183
Uniprot Name
Multidrug resistance protein 1
Molecular Weight
141477.255 Da
References
  1. Perloff ES, Duan SX, Skolnik PR, Greenblatt DJ, von Moltke LL: Atazanavir: effects on P-glycoprotein transport and CYP3A metabolism in vitro. Drug Metab Dispos. 2005 Jun;33(6):764-70. Epub 2005 Mar 11. [Article]
  2. Lucia MB, Golotta C, Rutella S, Rastrelli E, Savarino A, Cauda R: Atazanavir inhibits P-glycoprotein and multidrug resistance-associated protein efflux activity. J Acquir Immune Defic Syndr. 2005 Aug 15;39(5):635-7. [Article]
  3. Chinn LW, Gow JM, Tse MM, Becker SL, Kroetz DL: Interindividual variability in the effect of atazanavir and saquinavir on the expression of lymphocyte P-glycoprotein. J Antimicrob Chemother. 2007 Jul;60(1):61-7. Epub 2007 May 17. [Article]
  4. Wood R: Atazanavir: its role in HIV treatment. Expert Rev Anti Infect Ther. 2008 Dec;6(6):785-96. doi: 10.1586/14787210.6.6.785. [Article]
  5. Janneh O, Anwar T, Jungbauer C, Kopp S, Khoo SH, Back DJ, Chiba P: P-glycoprotein, multidrug resistance-associated proteins and human organic anion transporting polypeptide influence the intracellular accumulation of atazanavir. Antivir Ther. 2009;14(7):965-74. doi: 10.3851/IMP1399. [Article]
  6. Storch CH, Theile D, Lindenmaier H, Haefeli WE, Weiss J: Comparison of the inhibitory activity of anti-HIV drugs on P-glycoprotein. Biochem Pharmacol. 2007 May 15;73(10):1573-81. Epub 2007 Jan 24. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Transporter activity
Specific Function
Mediates export of organic anions and drugs from the cytoplasm. Mediates ATP-dependent transport of glutathione and glutathione conjugates, leukotriene C4, estradiol-17-beta-o-glucuronide, methotre...
Gene Name
ABCC1
Uniprot ID
P33527
Uniprot Name
Multidrug resistance-associated protein 1
Molecular Weight
171589.5 Da
References
  1. Janneh O, Anwar T, Jungbauer C, Kopp S, Khoo SH, Back DJ, Chiba P: P-glycoprotein, multidrug resistance-associated proteins and human organic anion transporting polypeptide influence the intracellular accumulation of atazanavir. Antivir Ther. 2009;14(7):965-74. doi: 10.3851/IMP1399. [Article]
  2. Lucia MB, Golotta C, Rutella S, Rastrelli E, Savarino A, Cauda R: Atazanavir inhibits P-glycoprotein and multidrug resistance-associated protein efflux activity. J Acquir Immune Defic Syndr. 2005 Aug 15;39(5):635-7. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Mediates the Na(+)-independent uptake of organic anions such as pravastatin, taurocholate, methotrexate, dehydroepiandrosterone sulfate, 17-beta-glucuronosyl estradiol, estrone sulfate, prostagland...
Gene Name
SLCO1B1
Uniprot ID
Q9Y6L6
Uniprot Name
Solute carrier organic anion transporter family member 1B1
Molecular Weight
76447.99 Da
References
  1. Karlgren M, Vildhede A, Norinder U, Wisniewski JR, Kimoto E, Lai Y, Haglund U, Artursson P: Classification of inhibitors of hepatic organic anion transporting polypeptides (OATPs): influence of protein expression on drug-drug interactions. J Med Chem. 2012 May 24;55(10):4740-63. doi: 10.1021/jm300212s. Epub 2012 May 15. [Article]
  2. Annaert P, Ye ZW, Stieger B, Augustijns P: Interaction of HIV protease inhibitors with OATP1B1, 1B3, and 2B1. Xenobiotica. 2010 Mar;40(3):163-76. doi: 10.3109/00498250903509375. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Mediates the Na(+)-independent uptake of organic anions such as 17-beta-glucuronosyl estradiol, taurocholate, triiodothyronine (T3), leukotriene C4, dehydroepiandrosterone sulfate (DHEAS), methotre...
Gene Name
SLCO1B3
Uniprot ID
Q9NPD5
Uniprot Name
Solute carrier organic anion transporter family member 1B3
Molecular Weight
77402.175 Da
References
  1. Karlgren M, Vildhede A, Norinder U, Wisniewski JR, Kimoto E, Lai Y, Haglund U, Artursson P: Classification of inhibitors of hepatic organic anion transporting polypeptides (OATPs): influence of protein expression on drug-drug interactions. J Med Chem. 2012 May 24;55(10):4740-63. doi: 10.1021/jm300212s. Epub 2012 May 15. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
General Function
Transporter activity
Specific Function
Involved in the ATP-dependent secretion of bile salts into the canaliculus of hepatocytes.
Gene Name
ABCB11
Uniprot ID
O95342
Uniprot Name
Bile salt export pump
Molecular Weight
146405.83 Da
References
  1. Pedersen JM, Matsson P, Bergstrom CA, Hoogstraate J, Noren A, LeCluyse EL, Artursson P: Early identification of clinically relevant drug interactions with the human bile salt export pump (BSEP/ABCB11). Toxicol Sci. 2013 Dec;136(2):328-43. doi: 10.1093/toxsci/kft197. Epub 2013 Sep 6. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Inhibitor
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Mediates the Na(+)-independent transport of organic anions such as taurocholate, the prostaglandins PGD2, PGE1, PGE2, leukotriene C4, thromboxane B2 and iloprost.
Gene Name
SLCO2B1
Uniprot ID
O94956
Uniprot Name
Solute carrier organic anion transporter family member 2B1
Molecular Weight
76709.98 Da
References
  1. Karlgren M, Vildhede A, Norinder U, Wisniewski JR, Kimoto E, Lai Y, Haglund U, Artursson P: Classification of inhibitors of hepatic organic anion transporting polypeptides (OATPs): influence of protein expression on drug-drug interactions. J Med Chem. 2012 May 24;55(10):4740-63. doi: 10.1021/jm300212s. Epub 2012 May 15. [Article]

Drug created at June 13, 2005 13:24 / Updated at July 22, 2024 03:26