Identification

Name
Atazanavir
Accession Number
DB01072  (APRD00804)
Type
Small Molecule
Groups
Approved, Investigational
Description

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.

Structure
Thumb
Synonyms
  • Atazanavirum
  • ATZ
External IDs
BMS-232632 / CGP-73547
Product Ingredients
IngredientUNIICASInChI Key
Atazanavir sulfate4MT4VIE29P229975-97-7DQSGVVGOPRWTKI-QVFAWCHISA-N
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
ReyatazCapsule100 mgOralBristol Myers SquibbNot applicableNot applicableCanada
ReyatazCapsule, gelatin coated300 mg/1OralRemedy Repack2017-05-09Not applicableUs
ReyatazCapsule300 mgOralBristol Myers Squibb Pharma Eeig2004-03-02Not applicableEu
ReyatazCapsule150 mgOralBristol Myers Squibb Pharma Eeig2004-03-02Not applicableEu
ReyatazCapsule150 mgOralBristol Myers Squibb2004-01-09Not applicableCanada
ReyatazCapsule, gelatin coated300 mg/1OralA-S Medication Solutions2003-06-24Not applicableUs
ReyatazCapsule, gelatin coated150 mg/1OralAvera McKennan Hospital2015-04-28Not applicableUs
ReyatazCapsule100 mgOralBristol Myers Squibb Pharma Eeig2004-03-02Not applicableEu
ReyatazCapsule, gelatin coated300 mg/1OralE.R. Squibb & Sons, L.L.C.2003-06-24Not applicableUs
ReyatazCapsule, gelatin coated200 mg/1OralA S Medication Solutions2003-06-24Not applicableUs
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
AtazanavirCapsule, gelatin coated200 mg/1OralCipla USA Inc.2018-09-14Not applicableUs
AtazanavirCapsule, gelatin coated200 mg/1OralGreenstone, Llc2018-01-02Not applicableUs
AtazanavirCapsule, gelatin coated150 mg/1OralGreenstone, Llc2018-01-02Not applicableUs
AtazanavirCapsule, gelatin coated150 mg/1OralCipla USA Inc.2018-09-14Not applicableUs
AtazanavirCapsule, gelatin coated300 mg/1OralCipla USA Inc.2018-09-14Not applicableUs
AtazanavirCapsule, gelatin coated300 mg/1OralGreenstone, Llc2018-01-02Not applicableUs
AtazanavirCapsule, gelatin coated100 mg/1OralCipla USA Inc.2018-08-09Not applicableUs
Atazanavir SulfateCapsule300 mg/1OralTeva2017-12-27Not applicableUs
Atazanavir SulfateCapsule300 mg/1OralAurobindo Pharma2018-06-25Not applicableUs
Atazanavir SulfateCapsule150 mg/1OralAurobindo Pharma2018-06-25Not applicableUs
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
EvotazAtazanavir sulfate (300 mg/1) + Cobicistat (150 mg/1)TabletOralE.R. Squibb & Sons, L.L.C.2015-01-29Not applicableUs
EvotazAtazanavir (300 mg) + Cobicistat (150 mg)TabletOralBristol Myers Squibb2016-02-11Not applicableCanada
EvotazAtazanavir sulfate (300 mg/1) + Cobicistat (150 mg/1)TabletOralA-S Medication Solutions2015-01-29Not applicableUs
EvotazAtazanavir sulfate (300 mg/1) + Cobicistat (150 mg/1)TabletOralA-S Medication Solutions2015-01-29Not applicableUs
International/Other Brands
Latazanavir / Zrivada
Categories
UNII
QZU4H47A3S
CAS number
198904-31-3
Weight
Average: 704.8555
Monoisotopic: 704.389748048
Chemical Formula
C38H52N6O7
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

Pharmacology

Indication

Used in combination with other antiretroviral agents for the treatment of HIV-1 infection, as well as postexposure prophylaxis of HIV infection in individuals who have had occupational or nonoccupational exposure to potentially infectious body fluids of a person known to be infected with HIV when that exposure represents a substantial risk for HIV transmission.

Associated Conditions
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.

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.

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. Administration of atazanavir with food enhances bioavailability and reduces pharmacokinetic variability. Oral bioavailability is 60-68%.

Volume of distribution
Not Available
Protein binding

86% bound to human serum proteins (alpha-1-acid glycoprotein and albumin). Protein binding is independent of concentration.

Metabolism

Atazanavir is extensively metabolized in humans, primarily by the liver. 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. In vitro studies using human liver microsomes suggested that atazanavir is metabolized by CYP3A.

Route of elimination
Not Available
Half life

Elimination half-life in adults (healthy and HIV infected) is approximately 7 hours (following a 400 mg daily dose with a light meal). Elimination half-life in hepatically impaired is 12.1 hours (following a single 400 mg dose).

Clearance
Not Available
Toxicity
Not Available
Affected organisms
  • Human Immunodeficiency Virus
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
DrugInteraction
(R)-warfarinThe metabolism of (R)-warfarin can be decreased when combined with Atazanavir.
(S)-WarfarinThe metabolism of (S)-Warfarin can be decreased when combined with Atazanavir.
2,4-thiazolidinedioneThe therapeutic efficacy of 2,4-thiazolidinedione can be decreased when used in combination with Atazanavir.
3,5-diiodothyropropionic acidThe metabolism of 3,5-diiodothyropropionic acid can be decreased when combined with Atazanavir.
4-hydroxycoumarinThe metabolism of 4-hydroxycoumarin can be decreased when combined with Atazanavir.
5-androstenedioneThe metabolism of 5-androstenedione can be decreased when combined with Atazanavir.
6-Deoxyerythronolide BThe metabolism of Atazanavir can be decreased when combined with 6-Deoxyerythronolide B.
6-O-benzylguanineThe metabolism of 6-O-benzylguanine can be decreased when combined with Atazanavir.
AbacavirThe metabolism of Abacavir can be decreased when combined with Atazanavir.
AbemaciclibThe metabolism of Abemaciclib can be decreased when combined with Atazanavir.
Food Interactions
  • Administration with food reduces pharmacokinetic variability.
  • Food increases product absorption.

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. [PubMed:19496633]
  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. [PubMed:18389089]
  3. Swainston Harrison T, Scott LJ: Atazanavir: a review of its use in the management of HIV infection. Drugs. 2005;65(16):2309-36. [PubMed:16266202]
  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. [PubMed:16176117]
  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. [PubMed:20116610]
  6. Busti AJ, Hall RG, Margolis DM: Atazanavir for the treatment of human immunodeficiency virus infection. Pharmacotherapy. 2004 Dec;24(12):1732-47. [PubMed:15585441]
External Links
Human Metabolome Database
HMDB0015205
KEGG Drug
D07471
PubChem Compound
148192
PubChem Substance
46508504
ChemSpider
130642
BindingDB
13934
ChEBI
37924
ChEMBL
CHEMBL1163
Therapeutic Targets Database
DNC000332
PharmGKB
PA10251
HET
DR7
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
PDRhealth
PDRhealth Drug Page
Wikipedia
Atazanavir
ATC Codes
J05AE08 — AtazanavirJ05AR15 — Atazanavir and cobicistat
AHFS Codes
  • 08:18.08.08 — HIV Protease Inhibitors
PDB Entries
2aqu / 2fxd / 2fxe / 2o4k / 3ekw / 3eky / 3el1 / 3el9 / 3em4 / 3oxx
FDA label
Download (412 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1Active Not RecruitingOtherHIV (Adult) / HIV in Adults1
1CompletedNot AvailableDiabetes, Diabetes Mellitus Type 11
1CompletedNot AvailableHealthy Volunteers2
1CompletedNot AvailableHepatitis C Viral Infection / Human Immunodeficiency Virus (HIV)1
1CompletedNot AvailableHuman Immunodeficiency Virus (HIV)1
1CompletedNot AvailableHuman Immunodeficiency Virus (HIV) Infections6
1CompletedNot AvailableHuman Immunodeficiency Virus (HIV) Infections / Human Immunodeficiency Virus Type 1 (HIV-1)1
1CompletedNot AvailableHuman Immunodeficiency Virus (HIV) Infections / Protease Inhibitors2
1CompletedNot AvailableHuman Immunodeficiency Virus (HIV) Infections / Substance Abuse1
1CompletedNot AvailableHuman Immunodeficiency Virus Type 1 (HIV-1)1
1CompletedBasic ScienceHealthy Volunteers1
1CompletedSupportive CareHuman Immunodeficiency Virus (HIV) Infections1
1CompletedTreatmentAntivirals/HIV1
1CompletedTreatmentChronic Hepatitis C Virus (HCV) Infection / Human Immunodeficiency Virus (HIV) Infections1
1CompletedTreatmentHealthy Volunteers3
1CompletedTreatmentHuman Immunodeficiency Virus (HIV)1
1CompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections4
1TerminatedHealth Services ResearchHuman Immunodeficiency Virus (HIV)1
1Unknown StatusBasic ScienceAtazanavir1
1, 2CompletedTreatmentHepatitis C Viral Infection / Human Immunodeficiency Virus (HIV)1
1, 2CompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections3
2Active Not RecruitingTreatmentHuman Immunodeficiency Virus (HIV) Infections1
2CompletedTreatmentAcquired Immune Deficiency Syndrome (AIDS) / Human Immunodeficiency Virus (HIV) Infections1
2CompletedTreatmentHuman Immunodeficiency Virus (HIV)1
2CompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections6
2CompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections / Human Immunodeficiency Virus Type 1 (HIV-1)1
2CompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections / Infection, Human Immunodeficiency Virus I1
2CompletedTreatmentInfection, Human Immunodeficiency Virus I2
2CompletedTreatmentType 2 Diabetes Mellitus Related Endothelial Dysfunction1
2TerminatedTreatmentHuman Immunodeficiency Virus (HIV)1
2TerminatedTreatmentHuman Immunodeficiency Virus (HIV) Infections1
2TerminatedTreatmentHuman Immunodeficiency Virus (HIV) Infections / Human Immunodeficiency Virus Infection(HIV)/Acquired Immunodeficiency Syndrome (AIDS)1
2TerminatedTreatmentInfection, Human Immunodeficiency Virus I1
2, 3CompletedBasic ScienceHuman Immunodeficiency Virus (HIV)1
2, 3CompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections1
2, 3CompletedTreatmentPeriodontitis, Chronic2
2, 3RecruitingTreatmentAcquired Immune Deficiency Syndrome (AIDS) / Human Immunodeficiency Virus (HIV) Infections1
3Active Not RecruitingTreatmentHuman Immunodeficiency Virus (HIV) Infections1
3Active Not RecruitingTreatmentHuman Immunodeficiency Virus (HIV) / Human Immunodeficiency Virus (HIV) Infections1
3Active Not RecruitingTreatmentInfection, Human Immunodeficiency Virus I2
3CompletedNot AvailableHuman Immunodeficiency Virus (HIV)1
3CompletedPreventionHuman Immunodeficiency Virus (HIV) Infections1
3CompletedTreatmentAcquired Immune Deficiency Syndrome (AIDS) / Human Immunodeficiency Virus (HIV) Infections2
3CompletedTreatmentAcquired Immune Deficiency Syndrome (AIDS) / Human Immunodeficiency Virus (HIV) / Human Immunodeficiency Virus (HIV) Infections1
3CompletedTreatmentHuman Immunodeficiency Virus (HIV)1
3CompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections14
3CompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections / Hyperlipidemias2
3CompletedTreatmentHuman Immunodeficiency Virus (HIV) / Human Immunodeficiency Virus (HIV) Infections2
3CompletedTreatmentInfection, Human Immunodeficiency Virus I1
3TerminatedTreatmentHuman Immunodeficiency Virus (HIV)1
3TerminatedTreatmentHuman Immunodeficiency Virus (HIV) Infections1
3WithdrawnTreatmentHuman Immunodeficiency Virus (HIV)2
3WithdrawnTreatmentHuman Immunodeficiency Virus (HIV) Infections1
4Active Not RecruitingTreatmentChronic Infection With HIV1
4Active Not RecruitingTreatmentHIV, Pediatric / Human Immunodeficiency Virus (HIV) Infections1
4Active Not RecruitingTreatmentHuman Immunodeficiency Virus (HIV)1
4CompletedNot AvailableHealthy Volunteers1
4CompletedNot AvailableHuman Immunodeficiency Virus (HIV)1
4CompletedNot AvailableHuman Immunodeficiency Virus (HIV) Infections1
4CompletedNot AvailableHuman Immunodeficiency Virus (HIV) / Proteinuria1
4CompletedOtherHuman Immunodeficiency Virus (HIV)1
4CompletedPreventionHuman Immunodeficiency Virus (HIV) Infections2
4CompletedTreatmentAlveolar Socket Preservations1
4CompletedTreatmentDyslipidemias / Human Immunodeficiency Virus (HIV) Infections1
4CompletedTreatmentHIV, Combination Therapy1
4CompletedTreatmentHIV, Pediatric1
4CompletedTreatmentHIV-Associated Lipodystrophy Syndrome1
4CompletedTreatmentHuman Immunodeficiency Virus (HIV)3
4CompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections15
4CompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections / Infection, Human Immunodeficiency Virus I1
4CompletedTreatmentHuman Immunodeficiency Virus Type 1 (HIV-1)1
4CompletedTreatmentImmunosuppression-related Infectious Disease / Infection, Human Immunodeficiency Virus I1
4CompletedTreatmentInfection, Human Immunodeficiency Virus I1
4CompletedTreatmentSocket Preservation1
4RecruitingTreatmentHuman Immunodeficiency Virus (HIV) Infections1
4TerminatedPreventionHuman Immunodeficiency Virus (HIV)1
4TerminatedTreatmentHuman Immunodeficiency Virus (HIV) Infections2
4TerminatedTreatmentHuman Immunodeficiency Virus (HIV) Infections / Mitochondrial Dysfunction1
4TerminatedTreatmentHuman Immunodeficiency Virus (HIV) Infections / Osteopenia1
4Unknown StatusTreatmentHepatitis C Viral Infection / Human Immunodeficiency Virus (HIV) Infections1
4Unknown StatusTreatmentHuman Immunodeficiency Virus (HIV) Infections1
4Unknown StatusTreatmentHuman Immunodeficiency Virus (HIV) Infections / Lipodystrophies1
4WithdrawnTreatmentHepatitis C Viral Infection / Human Immunodeficiency Virus (HIV)1
Not AvailableCompletedNot AvailableHuman Immunodeficiency Virus (HIV)1
Not AvailableCompletedNot AvailableHuman Immunodeficiency Virus (HIV) Infections3
Not AvailableCompletedNot AvailableInfection, Human Immunodeficiency Virus I1
Not AvailableCompletedOtherEndothelial Dysfunction1
Not AvailableCompletedTreatmentAcquired Immune Deficiency Syndrome (AIDS) / Human Immunodeficiency Virus (HIV) / Human Immunodeficiency Virus (HIV) Infections1
Not AvailableCompletedTreatmentEndotoxaemia / Inflammatory Reaction / Multi Organ Dysfunction Syndrome / Sepsis1
Not AvailableCompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections2
Not AvailableCompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections / Lipodystrophies / Wasting Disease1
Not AvailableCompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections / Tuberculosis Infection1
Not AvailableNo Longer AvailableNot AvailableHuman Immunodeficiency Virus (HIV) Infections1
Not AvailableRecruitingNot AvailableMinor Patient Treated by One or More Antiretroviral and for Which a Blood Test Has Been Performed1
Not AvailableUnknown StatusTreatmentHuman Immunodeficiency Virus (HIV)1
Not AvailableWithdrawnNot AvailableHIV-infected Patients1

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
CapsuleOral100 mg/1
CapsuleOral150 mg/1
CapsuleOral200 mg/1
CapsuleOral300 mg/1
TabletOral
CapsuleOral100 mg
CapsuleOral150 mg
CapsuleOral200 mg
CapsuleOral300 mg
Capsule, gelatin coatedOral100 mg/1
Capsule, gelatin coatedOral150 mg/1
Capsule, gelatin coatedOral200 mg/1
Capsule, gelatin coatedOral300 mg/1
PowderOral50 mg
PowderOral50 mg/1
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)
CA2250840No2006-07-042017-04-14Canada
CA2317736No2004-11-022018-12-22Canada
US5849911Yes1998-12-152017-12-20Us
US6087383Yes2000-07-112019-06-21Us
US8148374No2012-04-032029-09-03Us
US10039718No2012-10-042032-10-04Us

Properties

State
Solid
Experimental Properties
PropertyValueSource
water solubilityFree base slightly soluble (4-5 mg/mL)Not Available
logP4.5Not Available
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-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

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
Valine or derivatives / Alpha-amino acid amide / 2-phenylpyridine / Phenylbutylamine / Amphetamine or derivatives / Monocyclic benzene moiety / Fatty amide / N-acyl-amine / Fatty acyl / Benzenoid
show 21 more
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
carbohydrazide (CHEBI:37924)

Targets

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. [PubMed:17928344]
  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. [PubMed:17638694]
  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. [PubMed:19053892]
  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. [PubMed:16176117]
  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. [PubMed:18006837]
  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. [PubMed:18054799]
  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. [PubMed:20116610]
  8. Busti AJ, Hall RG, Margolis DM: Atazanavir for the treatment of human immunodeficiency virus infection. Pharmacotherapy. 2004 Dec;24(12):1732-47. [PubMed:15585441]
  9. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
Unknown
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. [PubMed:16176117]
  2. Busti AJ, Hall RG, Margolis DM: Atazanavir for the treatment of human immunodeficiency virus infection. Pharmacotherapy. 2004 Dec;24(12):1732-47. [PubMed:15585441]
  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. [PubMed:19515014]
  4. Atazanavir FDA Label [Link]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
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. [PubMed:15585441]
Kind
Protein
Organism
Human
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. [PubMed:20511137]
  2. Atazanavir FDA Label [Link]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
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]

Carriers

Kind
Protein
Organism
Human
Pharmacological action
Unknown
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. [PubMed:15814459]
  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. [PubMed:16336266]

Transporters

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
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. [PubMed:15764714]
  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. [PubMed:16044020]
  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. [PubMed:17510066]
  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. [PubMed:19053892]
  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. [PubMed:19918100]
  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. [PubMed:17328866]
Kind
Protein
Organism
Human
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. [PubMed:19918100]
  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. [PubMed:16044020]
Kind
Protein
Organism
Human
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. [PubMed:22541068]
  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. [PubMed:20102298]
Kind
Protein
Organism
Human
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. [PubMed:22541068]
Kind
Protein
Organism
Human
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. [PubMed:24014644]

Drug created on June 13, 2005 07:24 / Updated on November 18, 2018 13:31