Identification

Name
Venetoclax
Accession Number
DB11581
Description

Venetoclax is a BCL-2 inhibitor that was initially approved by the FDA in April 2016 Label. Proteins in the B cell CLL/lymphoma 2 (BCL-2) family are important regulators of the apoptotic (programmed cell death) process 1, 2. Venetoclax is used to treat chronic lymphocytic leukemia (CLL) and certain types of small lymphocytic lymphoma Label. CLL is the most prevalent leukemia diagnosed in Western countries 7. Venetoclax was developed through reverse engineering of the BCL-2 protein family inhibitor, navitoclax 7. Venetoclax is approximately 10 times more potent than navitoclax with regard to induction of apoptosis in CLL cells 7. A new indication was approved in 2018 for the treatment patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL), with or without 17p deletion, who have received at least one prior therapy Label. Previously, this drug was indicated only for patients with 17p gene deletion 10.

Type
Small Molecule
Groups
Approved, Investigational
Structure
Thumb
Weight
Average: 868.45
Monoisotopic: 867.3180959
Chemical Formula
C45H50ClN7O7S
Synonyms
  • 4-{4-[(4'-chloro-5,5-dimethyl[3,4,5,6-tetrahydro[1,1'-biphenyl]]-2-yl)methyl]piperazin-1-yl}-N-(3-nitro-4-{[(oxan-4-yl)methyl]amino}benzene-1-sulfonyl)-2-[(1H-pyrrolo[2,3-b]pyridin-5-yl)oxy]benzamide
  • Venetoclax
External IDs
  • ABT 199
  • ABT-199
  • ABT199
  • GDC-0199
  • GDC0199
  • RG-7601
  • RG7601

Pharmacology

Indication

A BCL-2 inhibitor indicated for the treatment of patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL), with or without 17p deletion, who have received at least one prior therapy Label.

Associated Conditions
Contraindications & Blackbox Warnings
Learn about our commercial Contraindications & Blackbox Warnings data.
Learn More
Pharmacodynamics

Venetoclax induces rapid and potent onset apoptosis of CLL cells, powerful enough to act within 24h and to lead to tumor lysis syndrome 5, Label, 2. Selective targeting of BCL2 with venetoclax has demonstrated a manageable safety profile and has been shown to induce significant response in patients with relapsed CLL (chronic lymphocytic leukemia) or SLL (small lymphocytic leukemia), including patients with poor prognostic features 6. This drug is not expected to have a significant impact on the cardiac QT interval Label. Venetoclax has demonstrated efficacy in various types of lymphoid malignancies, including relapsed/ refractory CLL harboring deletion 17p, with an overall response rate of approximately 80% 7.

Mechanism of action

Proteins in the B cell CLL/lymphoma 2 (BCL-2) family are necessary regulators of the apoptotic (anti-cell programmed death) process. This family comprises proapoptotic and prosurvival proteins for various cells. Cancer cells evade apoptosis by inhibiting programmed cell death (apoptosis). The therapeutic potential of directly inhibiting prosurvival proteins was unveiled with the development of navitoclax, a selective inhibitor of both BCL-2 and BCL-2-like 1 (BCL-X(L)), which has demonstrated clinical efficacy in some BCL-2-dependent hematological cancers 1. Selective inhibition of BCL-2 by venetoclax, sparing BCL-xL enables therapeutic induction of apoptosis without the negative effect of thrombocytopenia 7, 1. Venetoclax helps restore the process of apoptosis by binding directly to the BCL-2 protein, displacing pro-apoptotic proteins, leading to mitochondrial outer membrane permeabilization and the activation of caspase enzymes. In nonclinical studies, venetoclax has shown cytotoxic activity in tumor cells that overexpress BCL-2 Label.

TargetActionsOrganism
AApoptosis regulator Bcl-2
inhibitor
Humans
Absorption

Following several oral administrations after a meal, the maximum plasma concentration of venetoclax was reached 5-8 hours after the dose 3. Venetoclax steady state AUC (area under the curve) increased proportionally over the dose range of 150-800 mg. After a low-fat meal, venetoclax mean (± standard deviation) steady-state Cmax was 2.1 ± 1.1 μg/mL and AUC0-24 was 32.8 ± 16.9 μg•h/mL at the 400 mg once daily dose Label.

When compared with the fasted state, venetoclax exposure increased by 3.4 times when ingested with a low-fat meal and 5.2 times with a high-fat meal. When comparing low versus high fat, the Cmax and AUC were both increased by 50% when ingested with a high-fat meal. The FDA label indicataes that venetoclax should be taken with food 7, Label.

Volume of distribution

The population estimate for apparent volume of distribution (Vdss/F) of venetoclax ranged from 256-321 L Label.

Protein binding

Venetoclax is highly bound to human plasma protein with unbound fraction in plasma <0.01 across a concentration range of 1-30 µM (0.87-26 µg/mL). The mean blood-to-plasma ratio was 0.57 Label.

Metabolism

In vitro studies demonstrated that venetoclax is predominantly metabolized as a substrate of CYP3A4/5 Label, 4, 9.

Hover over products below to view reaction partners

Route of elimination

After single oral administration of 200 mg radiolabeled [14C]-venetoclax dose to healthy subjects, >99.9% of the dose was found in feces and <0.1% of the dose was excreted in urine within 9 days, suggesting that hepatic elimination is responsible for the clearance of venetoclax from systemic circulation. Unchanged venetoclax accounted for 20.8% of the radioactive dose excreted in feces Label.

Half-life

The half-life of venetoclax is reported to be 19-26 hours, after administration of a single 50-mg dose 7, Label.

Clearance

Mainly hepatic Label.

Adverse Effects
Learn about our commercial Adverse Effects data.
Learn More
Toxicity

Acute toxicity: oral toxicity (LD50) >2001 mg/kg (mouse) 8.

Venetoclax may cause embryo-fetal harm when administered to a pregnant woman. Patients should avoid pregnancy during treatment. A risk to human male fertility exists based on the results of testicular toxicity (germ cell loss) seen in dogs at exposures as low as 0.5 times the human AUC exposure at the recommended dose Label.

Carcinogenicity studies have not yet been performed with venetoclax Label.

Venetoclax was not shown to be mutagenic in an in vitro bacterial mutagenicity (Ames) assay, did not induce aberrations in an in vitro chromosome aberration assay with human peripheral blood lymphocytes. It was not clastogenic in an in vivo mouse bone marrow micronucleus assay at doses up to 835 mg/kg. The M27 metabolite was negative for genotoxic activity during both in vitro Ames and chromosome aberration assays Label.

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

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
AbametapirThe serum concentration of Venetoclax can be increased when it is combined with Abametapir.
AbataceptThe metabolism of Venetoclax can be increased when combined with Abatacept.
AbemaciclibVenetoclax may decrease the excretion rate of Abemaciclib which could result in a higher serum level.
AbirateroneThe metabolism of Abiraterone can be decreased when combined with Venetoclax.
AcalabrutinibThe metabolism of Acalabrutinib can be decreased when combined with Venetoclax.
AcenocoumarolThe serum concentration of Acenocoumarol can be increased when it is combined with Venetoclax.
AcetaminophenThe metabolism of Venetoclax can be increased when combined with Acetaminophen.
AcetazolamideThe metabolism of Venetoclax can be decreased when combined with Acetazolamide.
AdalimumabThe metabolism of Venetoclax can be increased when combined with Adalimumab.
AfatinibThe serum concentration of Afatinib can be increased when it is combined with Venetoclax.
Additional Data Available
  • Extended Description
    Extended Description

    Extended description of the mechanism of action and particular properties of each drug interaction.

    Learn more
  • Severity
    Severity

    A severity rating for each drug interaction, from minor to major.

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  • Evidence Level
    Evidence Level

    A rating for the strength of the evidence supporting each drug interaction.

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  • Action
    Action

    An effect category for each drug interaction. Know how this interaction affects the subject drug.

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Food Interactions
  • Avoid grapefruit products. Grapefruit inhibits CYP3A metabolism, which may increase the serum concentration of venetoclax.
  • Avoid St. John's Wort. This herb induces CYP3A metabolism and may reduce serum levels of venetoclax.
  • Take at the same time every day.
  • Take with a full glass of water.
  • Take with food.

Products

Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
VenclextaTablet10 mgOralAbbvie2016-10-31Not applicableCanada flag
VenclextaTablet, film coated10 mg/1OralAbbVie Inc.2016-04-11Not applicableUS flag
VenclextaTablet100 mgOralAbbvie2016-10-31Not applicableCanada flag
VenclextaTablet, film coated100 mg/1OralAbbVie Inc.2016-04-11Not applicableUS flag
VenclextaTablet50 mgOralAbbvie2016-10-31Not applicableCanada flag
VenclextaTablet, film coated50 mg/1OralAbbVie Inc.2016-04-11Not applicableUS flag
Additional Data Available
  • Application Number
    Application Number

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

    Learn more
  • Product Code
    Product Code

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

    Learn more
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing EndRegionImage
VenclextaVenetoclax (10 mg) + Venetoclax (50 mg) + Venetoclax (100 mg)Kit; TabletOralAbbvie2016-10-31Not applicableCanada flag
VenclextaVenetoclax (10 mg/1) + Venetoclax (50 mg/1) + Venetoclax (100 mg/1) + Venetoclax (100 mg/1)OralAbbVie Inc.2016-04-11Not applicableUS flag
VenclextaVenetoclax (10 mg) + Venetoclax (50 mg) + Venetoclax (100 mg)Kit; TabletOralAbbvie2016-10-31Not applicableCanada flag
VenclextaVenetoclax (10 mg/1) + Venetoclax (50 mg/1) + Venetoclax (100 mg/1) + Venetoclax (100 mg/1)OralAbbVie Inc.2016-04-11Not applicableUS flag
VenclextaVenetoclax (10 mg/1) + Venetoclax (50 mg/1) + Venetoclax (100 mg/1) + Venetoclax (100 mg/1)OralAbbVie Inc.2016-04-11Not applicableUS flag
VenclextaVenetoclax (10 mg) + Venetoclax (50 mg) + Venetoclax (100 mg)Kit; TabletOralAbbvie2016-10-31Not applicableCanada flag
VenclextaVenetoclax (10 mg/1) + Venetoclax (50 mg/1) + Venetoclax (100 mg/1) + Venetoclax (100 mg/1)OralAbbVie Inc.2016-04-11Not applicableUS flag

Categories

ATC Codes
L01XX52 — Venetoclax
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as phenylpiperazines. These are compounds containing a phenylpiperazine skeleton, which consists of a piperazine bound to a phenyl group.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Diazinanes
Sub Class
Piperazines
Direct Parent
Phenylpiperazines
Alternative Parents
N-arylpiperazines / Aminobenzenesulfonamides / Diarylethers / Aminobenzoic acids and derivatives / Pyrrolopyridines / Benzenesulfonyl compounds / Nitrobenzenes / Aniline and substituted anilines / Benzoyl derivatives / Dialkylarylamines
show 26 more
Substituents
Allyl-type 1,3-dipolar organic compound / Amine / Amino acid or derivatives / Aminobenzenesulfonamide / Aminobenzoic acid or derivatives / Aminosulfonyl compound / Aniline or substituted anilines / Aromatic heteropolycyclic compound / Aryl chloride / Aryl halide
show 52 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
Not Available

Chemical Identifiers

UNII
N54AIC43PW
CAS number
1257044-40-8
InChI Key
LQBVNQSMGBZMKD-UHFFFAOYSA-N
InChI
InChI=1S/C45H50ClN7O7S/c1-45(2)15-11-33(39(26-45)31-3-5-34(46)6-4-31)29-51-17-19-52(20-18-51)35-7-9-38(42(24-35)60-36-23-32-12-16-47-43(32)49-28-36)44(54)50-61(57,58)37-8-10-40(41(25-37)53(55)56)48-27-30-13-21-59-22-14-30/h3-10,12,16,23-25,28,30,48H,11,13-15,17-22,26-27,29H2,1-2H3,(H,47,49)(H,50,54)
IUPAC Name
4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-1-yl]methyl}piperazin-1-yl)-N-(3-nitro-4-{[(oxan-4-yl)methyl]amino}benzenesulfonyl)-2-{1H-pyrrolo[2,3-b]pyridin-5-yloxy}benzamide
SMILES
CC1(C)CCC(CN2CCN(CC2)C2=CC=C(C(=O)NS(=O)(=O)C3=CC=C(NCC4CCOCC4)C(=C3)[N+]([O-])=O)C(OC3=CN=C4NC=CC4=C3)=C2)=C(C1)C1=CC=C(Cl)C=C1

References

General References
  1. Souers AJ, Leverson JD, Boghaert ER, Ackler SL, Catron ND, Chen J, Dayton BD, Ding H, Enschede SH, Fairbrother WJ, Huang DC, Hymowitz SG, Jin S, Khaw SL, Kovar PJ, Lam LT, Lee J, Maecker HL, Marsh KC, Mason KD, Mitten MJ, Nimmer PM, Oleksijew A, Park CH, Park CM, Phillips DC, Roberts AW, Sampath D, Seymour JF, Smith ML, Sullivan GM, Tahir SK, Tse C, Wendt MD, Xiao Y, Xue JC, Zhang H, Humerickhouse RA, Rosenberg SH, Elmore SW: ABT-199, a potent and selective BCL-2 inhibitor, achieves antitumor activity while sparing platelets. Nat Med. 2013 Feb;19(2):202-8. doi: 10.1038/nm.3048. Epub 2013 Jan 6. [PubMed:23291630]
  2. Cang S, Iragavarapu C, Savooji J, Song Y, Liu D: ABT-199 (venetoclax) and BCL-2 inhibitors in clinical development. J Hematol Oncol. 2015 Nov 20;8:129. doi: 10.1186/s13045-015-0224-3. [PubMed:26589495]
  3. Salem AH, Agarwal SK, Dunbar M, Enschede SL, Humerickhouse RA, Wong SL: Pharmacokinetics of Venetoclax, a Novel BCL-2 Inhibitor, in Patients with Relapsed or Refractory Chronic Lymphocytic Leukemia or Non-Hodgkin's Lymphoma. J Clin Pharmacol. 2016 Aug 25. doi: 10.1002/jcph.821. [PubMed:27558232]
  4. Agarwal SK, Hu B, Chien D, Wong SL, Salem AH: Evaluation of Rifampin's Transporter Inhibitory and CYP3A Inductive Effects on the Pharmacokinetics of Venetoclax, a Bcl-2 Inhibitor: Results of a Single- and Multiple-dose Study. J Clin Pharmacol. 2016 Mar 7. doi: 10.1002/jcph.730. [PubMed:26953185]
  5. Anderson MA, Deng J, Seymour JF, Tam C, Kim SY, Fein J, Yu L, Brown JR, Westerman D, Si EG, Majewski IJ, Segal D, Heitner Enschede SL, Huang DC, Davids MS, Letai A, Roberts AW: The BCL2 selective inhibitor venetoclax induces rapid onset apoptosis of CLL cells in patients via a TP53-independent mechanism. Blood. 2016 Jun 23;127(25):3215-24. doi: 10.1182/blood-2016-01-688796. Epub 2016 Apr 11. [PubMed:27069256]
  6. Roberts AW, Davids MS, Pagel JM, Kahl BS, Puvvada SD, Gerecitano JF, Kipps TJ, Anderson MA, Brown JR, Gressick L, Wong S, Dunbar M, Zhu M, Desai MB, Cerri E, Heitner Enschede S, Humerickhouse RA, Wierda WG, Seymour JF: Targeting BCL2 with Venetoclax in Relapsed Chronic Lymphocytic Leukemia. N Engl J Med. 2016 Jan 28;374(4):311-22. doi: 10.1056/NEJMoa1513257. Epub 2015 Dec 6. [PubMed:26639348]
  7. King AC, Peterson TJ, Horvat TZ, Rodriguez M, Tang LA: Venetoclax: A First-in-Class Oral BCL-2 Inhibitor for the Management of Lymphoid Malignancies. Ann Pharmacother. 2017 May;51(5):410-416. doi: 10.1177/1060028016685803. Epub 2017 Jan 6. [PubMed:28056525]
  8. Venetoclax, Safety Sheet [Link]
  9. Australian Product Information: Venetoclax [File]
  10. Venetoclax, Previous FDA label [File]
KEGG Drug
D10679
PubChem Compound
49846579
PubChem Substance
347827991
ChemSpider
29315017
BindingDB
60828
RxNav
1747556
ChEBI
133021
ChEMBL
CHEMBL3137309
ZINC
ZINC000150338755
PharmGKB
PA166153473
PDBe Ligand
LBM
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Venetoclax
AHFS Codes
  • 10:00.00 — Antineoplastic Agents
PDB Entries
6o0k / 6o0l / 6o0m / 6o0p
FDA label
Download (1.31 MB)
MSDS
Download (230 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
3Active Not RecruitingTreatmentAcute Myeloid Leukemia (AML)2
3Active Not RecruitingTreatmentChronic Lymphocytic Leukaemia (CLL)5
3Active Not RecruitingTreatmentChronic Lymphocytic Leukaemia (CLL) / Small Lymphocytic Lymphoma1
3Active Not RecruitingTreatmentLeukemia, Lymphocytic, Chronic, B-Cell1
3Enrolling by InvitationTreatmentAcute Lymphoblastic Leukaemias (ALL) / Acute Myeloid Leukemia (AML) / Chronic Lymphocytic Leukaemia (CLL) / Malignancies / Multiple Myeloma (MM) / Non-Hodgkin's Lymphoma (NHL)1
3Not Yet RecruitingTreatmentChronic Lymphocytic Leukaemia (CLL) / Small Lymphocytic Lymphoma1
3RecruitingTreatmentAcute Myeloid Leukemia (AML)3
3RecruitingTreatmentAcute Myeloid Leukemia (AML) / Malignancies2
3RecruitingTreatmentChronic Lymphocytic Leukaemia (CLL)3
3RecruitingTreatmentChronic Lymphocytic Leukaemia (CLL) / Small Lymphocytic Lymphoma2

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
Kit; tabletOral
TabletOral10 mg
TabletOral100 mg
TabletOral50 mg
Tablet, coatedOral10 mg
Tablet, film coatedOral10 mg/1
Tablet, film coatedOral100 mg/1
Tablet, film coatedOral50 mg/1
Tablet
Tablet, film coatedOral10 MG
Tablet, film coatedOral100 MG
Tablet, film coatedOral50 MG
Tablet, coated10 mg
Tablet, coated100 mg
Tablet, coated50 mg
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)Region
US9174982No2015-11-032030-05-26US flag
US8546399No2013-10-012031-06-27US flag
US9539251No2017-01-102033-09-06US flag
US8722657No2014-05-132032-01-29US flag
US10730873No2011-11-212031-11-21US flag
Additional Data Available
  • Filed On
    Filed On

    The date on which a patent was filed with the relevant government.

    Learn more

Properties

State
Solid
Experimental Properties
PropertyValueSource
logP99MSDS
Predicted Properties
PropertyValueSource
Water Solubility0.000933 mg/mLALOGPS
logP6.92ALOGPS
logP6.76ChemAxon
logS-6ALOGPS
pKa (Strongest Acidic)4.19ChemAxon
pKa (Strongest Basic)7.96ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count10ChemAxon
Hydrogen Donor Count3ChemAxon
Polar Surface Area172.03 Å2ChemAxon
Rotatable Bond Count12ChemAxon
Refractivity238.59 m3·mol-1ChemAxon
Polarizability93.95 Å3ChemAxon
Number of Rings8ChemAxon
Bioavailability0ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET Features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
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

Targets

Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
General Function
Ubiquitin protein ligase binding
Specific Function
Suppresses apoptosis in a variety of cell systems including factor-dependent lymphohematopoietic and neural cells. Regulates cell death by controlling the mitochondrial membrane permeability. Appea...
Gene Name
BCL2
Uniprot ID
P10415
Uniprot Name
Apoptosis regulator Bcl-2
Molecular Weight
26265.66 Da
References
  1. Davids MS, Letai A: ABT-199: taking dead aim at BCL-2. Cancer Cell. 2013 Feb 11;23(2):139-41. doi: 10.1016/j.ccr.2013.01.018. [PubMed:23410971]
  2. Souers AJ, Leverson JD, Boghaert ER, Ackler SL, Catron ND, Chen J, Dayton BD, Ding H, Enschede SH, Fairbrother WJ, Huang DC, Hymowitz SG, Jin S, Khaw SL, Kovar PJ, Lam LT, Lee J, Maecker HL, Marsh KC, Mason KD, Mitten MJ, Nimmer PM, Oleksijew A, Park CH, Park CM, Phillips DC, Roberts AW, Sampath D, Seymour JF, Smith ML, Sullivan GM, Tahir SK, Tse C, Wendt MD, Xiao Y, Xue JC, Zhang H, Humerickhouse RA, Rosenberg SH, Elmore SW: ABT-199, a potent and selective BCL-2 inhibitor, achieves antitumor activity while sparing platelets. Nat Med. 2013 Feb;19(2):202-8. doi: 10.1038/nm.3048. Epub 2013 Jan 6. [PubMed:23291630]
  3. King AC, Peterson TJ, Horvat TZ, Rodriguez M, Tang LA: Venetoclax: A First-in-Class Oral BCL-2 Inhibitor for the Management of Lymphoid Malignancies. Ann Pharmacother. 2017 May;51(5):410-416. doi: 10.1177/1060028016685803. Epub 2017 Jan 6. [PubMed:28056525]

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. Agarwal SK, Hu B, Chien D, Wong SL, Salem AH: Evaluation of Rifampin's Transporter Inhibitory and CYP3A Inductive Effects on the Pharmacokinetics of Venetoclax, a Bcl-2 Inhibitor: Results of a Single- and Multiple-dose Study. J Clin Pharmacol. 2016 Mar 7. doi: 10.1002/jcph.730. [PubMed:26953185]
  2. Weiss J, Gajek T, Kohler BC, Haefeli WE: Venetoclax (ABT-199) Might Act as a Perpetrator in Pharmacokinetic Drug-Drug Interactions. Pharmaceutics. 2016 Feb 24;8(1). pii: pharmaceutics8010005. doi: 10.3390/pharmaceutics8010005. [PubMed:26927160]
  3. Freise KJ, Hu B, Salem AH: Impact of ritonavir dose and schedule on CYP3A inhibition and venetoclax clinical pharmacokinetics. Eur J Clin Pharmacol. 2018 Apr;74(4):413-421. doi: 10.1007/s00228-017-2403-3. Epub 2018 Jan 4. [PubMed:29302721]
  4. Venclexta FDA label [File]

Transporters

Kind
Protein
Organism
Humans
Pharmacological action
No
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. Agarwal SK, Hu B, Chien D, Wong SL, Salem AH: Evaluation of Rifampin's Transporter Inhibitory and CYP3A Inductive Effects on the Pharmacokinetics of Venetoclax, a Bcl-2 Inhibitor: Results of a Single- and Multiple-dose Study. J Clin Pharmacol. 2016 Mar 7. doi: 10.1002/jcph.730. [PubMed:26953185]
  2. Australian Product Information, Venetoclax [File]
  3. Venclexta FDA label [File]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Xenobiotic-transporting atpase activity
Specific Function
High-capacity urate exporter functioning in both renal and extrarenal urate excretion. Plays a role in porphyrin homeostasis as it is able to mediates the export of protoporhyrin IX (PPIX) both fro...
Gene Name
ABCG2
Uniprot ID
Q9UNQ0
Uniprot Name
ATP-binding cassette sub-family G member 2
Molecular Weight
72313.47 Da
References
  1. Venclexta FDA label [File]
  2. FDA label, Venclexta [File]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
Curator comments
Data supported only by in vitro evidence.
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. Weiss J, Gajek T, Kohler BC, Haefeli WE: Venetoclax (ABT-199) Might Act as a Perpetrator in Pharmacokinetic Drug-Drug Interactions. Pharmaceutics. 2016 Feb 24;8(1). pii: pharmaceutics8010005. doi: 10.3390/pharmaceutics8010005. [PubMed:26927160]
  2. FDA label, Venclexta [File]

Drug created on April 18, 2016 10:22 / Updated on October 19, 2020 07:46

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