Identification

Name
Venetoclax
Accession Number
DB11581
Type
Small Molecule
Groups
Approved
Description

Venetoclax is an oral selective inhibitor of B-Cell Lymphoma-2 (BCL-2), an antiapoptotic protein that plays a key role in the development of chronic lymphocytic leukemia (CLL) cells. BCL-2 and its related proteins BCL-XL and MCL-1 bind to and sequester pro-apoptotic signals in the cell, causing a down-regulation of apoptosis. As an oncogene and an important regulator of apoptosis, BCL-2 overexpression therefore results in increased tumour cell survival and resistance to chemotherapy. Venetoclax helps restore the process of apoptosis by binding directly to the BCL-2 protein, displacing pro-apoptotic proteins like BIM, triggering mitochondrial outer membrane permeabilization and the activation of caspases. Compared to navitoclax, a duel inhibitor of BCL-2 and BCL-XL, venetoclax use results in significantly less platelet killing and thrombocytopenia. This is due to its specificity for BCL-2 and sparing of BCL-XL, which is required for platelet survival.

In 2015, the United States Food and Drug Administration (FDA) granted Breakthrough Therapy Designation to venetoclax for patients with CLL who have relapsed or have been refractory to previous treatment and have the 17p deletion genetic mutation. It was approved by the FDA in April 2016.

Structure
Thumb
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
External IDs
ABT 199 / ABT-199 / ABT199 / GDC-0199 / GDC0199 / RG-7601 / RG7601
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
VenclextaTablet10 mgOralAbbvie2016-10-31Not applicableCanada
VenclextaTablet, film coated10 mg/1OralAbbvie2016-04-11Not applicableUs
VenclextaKitAbbvie2016-04-11Not applicableUs
VenclextaTablet50 mgOralAbbvie2016-10-31Not applicableCanada
VenclextaTablet, film coated50 mg/1OralAbbvie2016-04-11Not applicableUs
VenclextaTablet100 mgOralAbbvie2016-10-31Not applicableCanada
VenclextaTablet, film coated100 mg/1OralAbbvie2016-04-11Not applicableUs
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
VenclextaVenetoclax (10 mg) + Venetoclax (100 mg) + Venetoclax (50 mg)Kit; TabletOralAbbvie2016-10-31Not applicableCanada
VenclextaVenetoclax (10 mg) + Venetoclax (100 mg) + Venetoclax (50 mg)Kit; TabletOralAbbvie2016-10-31Not applicableCanada
VenclextaVenetoclax (10 mg) + Venetoclax (100 mg) + Venetoclax (50 mg)Kit; TabletOralAbbvie2016-10-31Not applicableCanada
Categories
UNII
N54AIC43PW
CAS number
1257044-40-8
Weight
Average: 868.45
Monoisotopic: 867.3180959
Chemical Formula
C45H50ClN7O7S
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

Pharmacology

Indication

For the treatment of patients with chronic lymphocytic leukemia (CLL) with 17p deletion, as detected by an FDA approved test, who have received at least one prior therapy.

Structured Indications
Pharmacodynamics

Venetoclax has not been shown to have an effect on QTc interval.

Mechanism of action

Venetoclax is a selective and orally bioavailable small-molecule inhibitor of BCL-2, an anti-apoptotic protein. Overexpression of BCL-2 has been demonstrated in CLL cells where it mediates tumor cell survival and has been associated with resistance to chemotherapeutics. Venetoclax helps restore the process of apoptosis by binding directly to the BCL-2 protein, displacing pro-apoptotic proteins like BIM, triggering mitochondrial outer membrane permeabilization and the activation of caspases. In nonclinical studies, venetoclax has demonstrated cytotoxic activity in tumor cells that overexpress BCL-2.

TargetActionsOrganism
AApoptosis regulator Bcl-2
inhibitor
Human
Absorption

Following multiple oral administrations under fed conditions, maximum plasma concentration of venetoclax was reached 5-8 hours after dose with a Cmax of 2.1 ± 1.1 μg/mL.

Volume of distribution

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

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.

Metabolism

In vitro studies demonstrated that venetoclax is predominantly metabolized by CYP3A4/5. M27 was identified as a major metabolite in plasma with an inhibitory activity against BCL-2 that is at least 58-fold lower than venetoclax in vitro

Reactions:
Route of elimination

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

Half life

26 hr

Clearance
Not Available
Toxicity

The most common adverse reactions (≥20%) were neutropenia, diarrhea, nausea, anemia, upper respiratory tract infection, thrombocytopenia, and fatigue. Patients should be monitored for development of tumor lysis syndrome and neutorpenia. Venetoclax may cause embryo-fetal harm when administered to a pregnant woman. Patients should therefore avoid pregnancy during treatment.

Affected organisms
Not Available
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteractionDrug group
AcetyldigitoxinAcetyldigitoxin may decrease the cardiotoxic activities of Venetoclax.Approved
AcetyldigoxinAcetyldigoxin may decrease the cardiotoxic activities of Venetoclax.Experimental
AmiodaroneThe metabolism of Venetoclax can be decreased when combined with Amiodarone.Approved, Investigational
AprepitantThe serum concentration of Venetoclax can be increased when it is combined with Aprepitant.Approved, Investigational
AtazanavirThe metabolism of Venetoclax can be decreased when combined with Atazanavir.Approved, Investigational
AtomoxetineThe metabolism of Venetoclax can be decreased when combined with Atomoxetine.Approved
BevacizumabBevacizumab may increase the cardiotoxic activities of Venetoclax.Approved, Investigational
BoceprevirThe metabolism of Venetoclax can be decreased when combined with Boceprevir.Approved, Withdrawn
BortezomibThe metabolism of Venetoclax can be decreased when combined with Bortezomib.Approved, Investigational
BosentanThe serum concentration of Venetoclax can be decreased when it is combined with Bosentan.Approved, Investigational
CabazitaxelThe risk or severity of adverse effects can be increased when Cabazitaxel is combined with Venetoclax.Approved
CarbamazepineThe metabolism of Venetoclax can be increased when combined with Carbamazepine.Approved, Investigational
CeritinibThe serum concentration of Venetoclax can be increased when it is combined with Ceritinib.Approved
ClarithromycinThe metabolism of Venetoclax can be decreased when combined with Clarithromycin.Approved
ClemastineThe metabolism of Venetoclax can be decreased when combined with Clemastine.Approved
ClotrimazoleThe metabolism of Venetoclax can be decreased when combined with Clotrimazole.Approved, Vet Approved
CobicistatThe metabolism of Venetoclax can be decreased when combined with Cobicistat.Approved
ConivaptanThe serum concentration of Venetoclax can be increased when it is combined with Conivaptan.Approved, Investigational
CrizotinibThe metabolism of Venetoclax can be decreased when combined with Crizotinib.Approved
CyclophosphamideCyclophosphamide may increase the cardiotoxic activities of Venetoclax.Approved, Investigational
CyclosporineThe metabolism of Venetoclax can be decreased when combined with Cyclosporine.Approved, Investigational, Vet Approved
CymarinCymarin may decrease the cardiotoxic activities of Venetoclax.Experimental
DabrafenibThe serum concentration of Venetoclax can be decreased when it is combined with Dabrafenib.Approved
DarunavirThe metabolism of Venetoclax can be decreased when combined with Darunavir.Approved
DasatinibThe serum concentration of Venetoclax can be increased when it is combined with Dasatinib.Approved, Investigational
DeferasiroxThe serum concentration of Venetoclax can be decreased when it is combined with Deferasirox.Approved, Investigational
DelavirdineThe metabolism of Venetoclax can be decreased when combined with Delavirdine.Approved
DeslanosideDeslanoside may decrease the cardiotoxic activities of Venetoclax.Approved
DigitoxinDigitoxin may decrease the cardiotoxic activities of Venetoclax.Approved, Investigational
DigoxinDigoxin may decrease the cardiotoxic activities of Venetoclax.Approved
Digoxin Immune Fab (Ovine)Digoxin Immune Fab (Ovine) may decrease the cardiotoxic activities of Venetoclax.Approved
DihydroergotamineThe metabolism of Venetoclax can be decreased when combined with Dihydroergotamine.Approved
DiltiazemThe metabolism of Venetoclax can be decreased when combined with Diltiazem.Approved
DocetaxelThe risk or severity of adverse effects can be increased when Docetaxel is combined with Venetoclax.Approved, Investigational
DoxycyclineThe metabolism of Venetoclax can be decreased when combined with Doxycycline.Approved, Investigational, Vet Approved
DronedaroneThe metabolism of Venetoclax can be decreased when combined with Dronedarone.Approved
EltrombopagThe serum concentration of Venetoclax can be increased when it is combined with Eltrombopag.Approved
EnzalutamideThe serum concentration of Venetoclax can be decreased when it is combined with Enzalutamide.Approved
ErythromycinThe metabolism of Venetoclax can be decreased when combined with Erythromycin.Approved, Vet Approved
FluconazoleThe metabolism of Venetoclax can be decreased when combined with Fluconazole.Approved
FluvoxamineThe metabolism of Venetoclax can be decreased when combined with Fluvoxamine.Approved, Investigational
FosamprenavirThe metabolism of Venetoclax can be decreased when combined with Fosamprenavir.Approved
FosaprepitantThe serum concentration of Venetoclax can be increased when it is combined with Fosaprepitant.Approved
FosphenytoinThe metabolism of Venetoclax can be increased when combined with Fosphenytoin.Approved
Fusidic AcidThe serum concentration of Venetoclax can be increased when it is combined with Fusidic Acid.Approved
GitoformateGitoformate may decrease the cardiotoxic activities of Venetoclax.Experimental
IdelalisibThe serum concentration of Venetoclax can be increased when it is combined with Idelalisib.Approved
ImatinibThe metabolism of Venetoclax can be decreased when combined with Imatinib.Approved
IndinavirThe metabolism of Venetoclax can be decreased when combined with Indinavir.Approved
IsavuconazoniumThe metabolism of Venetoclax can be decreased when combined with Isavuconazonium.Approved, Investigational
IsradipineThe metabolism of Venetoclax can be decreased when combined with Isradipine.Approved
ItraconazoleThe metabolism of Venetoclax can be decreased when combined with Itraconazole.Approved, Investigational
IvacaftorThe serum concentration of Venetoclax can be increased when it is combined with Ivacaftor.Approved
KetoconazoleThe metabolism of Venetoclax can be decreased when combined with Ketoconazole.Approved, Investigational
Lanatoside CLanatoside C may decrease the cardiotoxic activities of Venetoclax.Experimental
LopinavirThe metabolism of Venetoclax can be decreased when combined with Lopinavir.Approved
LovastatinThe metabolism of Venetoclax can be decreased when combined with Lovastatin.Approved, Investigational
LuliconazoleThe serum concentration of Venetoclax can be increased when it is combined with Luliconazole.Approved
LumacaftorThe serum concentration of Venetoclax can be decreased when it is combined with Lumacaftor.Approved
MetildigoxinMetildigoxin may decrease the cardiotoxic activities of Venetoclax.Experimental
MifepristoneThe serum concentration of Venetoclax can be increased when it is combined with Mifepristone.Approved, Investigational
MitotaneThe serum concentration of Venetoclax can be decreased when it is combined with Mitotane.Approved
NefazodoneThe metabolism of Venetoclax can be decreased when combined with Nefazodone.Approved, Withdrawn
NelfinavirThe metabolism of Venetoclax can be decreased when combined with Nelfinavir.Approved
NetupitantThe serum concentration of Venetoclax can be increased when it is combined with Netupitant.Approved
NevirapineThe metabolism of Venetoclax can be increased when combined with Nevirapine.Approved
NilotinibThe metabolism of Venetoclax can be decreased when combined with Nilotinib.Approved, Investigational
OlaparibThe metabolism of Venetoclax can be decreased when combined with Olaparib.Approved
OleandrinOleandrin may decrease the cardiotoxic activities of Venetoclax.Experimental, Investigational
OsimertinibThe serum concentration of Venetoclax can be increased when it is combined with Osimertinib.Approved
OuabainOuabain may decrease the cardiotoxic activities of Venetoclax.Approved
PaclitaxelThe risk or severity of adverse effects can be increased when Paclitaxel is combined with Venetoclax.Approved, Vet Approved
PalbociclibThe serum concentration of Venetoclax can be increased when it is combined with Palbociclib.Approved
PentobarbitalThe metabolism of Venetoclax can be increased when combined with Pentobarbital.Approved, Vet Approved
PeruvosidePeruvoside may decrease the cardiotoxic activities of Venetoclax.Experimental
PhenobarbitalThe metabolism of Venetoclax can be increased when combined with Phenobarbital.Approved
PhenytoinThe metabolism of Venetoclax can be increased when combined with Phenytoin.Approved, Vet Approved
PosaconazoleThe metabolism of Venetoclax can be decreased when combined with Posaconazole.Approved, Investigational, Vet Approved
PrimidoneThe metabolism of Venetoclax can be increased when combined with Primidone.Approved, Vet Approved
ProscillaridinProscillaridin may decrease the cardiotoxic activities of Venetoclax.Experimental
RanolazineThe serum concentration of Venetoclax can be increased when it is combined with Ranolazine.Approved, Investigational
RifabutinThe metabolism of Venetoclax can be increased when combined with Rifabutin.Approved
RifampicinThe metabolism of Venetoclax can be increased when combined with Rifampicin.Approved
RifapentineThe metabolism of Venetoclax can be increased when combined with Rifapentine.Approved
RolapitantThe serum concentration of Venetoclax can be increased when it is combined with Rolapitant.Approved
SaquinavirThe metabolism of Venetoclax can be decreased when combined with Saquinavir.Approved, Investigational
SildenafilThe metabolism of Venetoclax can be decreased when combined with Sildenafil.Approved, Investigational
SiltuximabThe serum concentration of Venetoclax can be decreased when it is combined with Siltuximab.Approved
SimeprevirThe serum concentration of Venetoclax can be increased when it is combined with Simeprevir.Approved
St. John's WortThe serum concentration of Venetoclax can be decreased when it is combined with St. John&#39;s Wort.Investigational, Nutraceutical
StiripentolThe serum concentration of Venetoclax can be increased when it is combined with Stiripentol.Approved
SulfisoxazoleThe metabolism of Venetoclax can be decreased when combined with Sulfisoxazole.Approved, Vet Approved
TelaprevirThe metabolism of Venetoclax can be decreased when combined with Telaprevir.Approved, Withdrawn
TelithromycinThe metabolism of Venetoclax can be decreased when combined with Telithromycin.Approved
TeriflunomideThe serum concentration of Venetoclax can be increased when it is combined with Teriflunomide.Approved
TiclopidineThe metabolism of Venetoclax can be decreased when combined with Ticlopidine.Approved
TocilizumabThe serum concentration of Venetoclax can be decreased when it is combined with Tocilizumab.Approved
TrastuzumabTrastuzumab may increase the cardiotoxic activities of Venetoclax.Approved, Investigational
VenlafaxineThe metabolism of Venetoclax can be decreased when combined with Venlafaxine.Approved
VerapamilThe metabolism of Venetoclax can be decreased when combined with Verapamil.Approved
VoriconazoleThe metabolism of Venetoclax can be decreased when combined with Voriconazole.Approved, Investigational
ZiprasidoneThe metabolism of Venetoclax can be decreased when combined with Ziprasidone.Approved
Food Interactions
Not Available

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]
External Links
KEGG Drug
D10679
PubChem Compound
49846579
PubChem Substance
347827991
ChemSpider
29315017
BindingDB
60828
ChEBI
133021
ChEMBL
CHEMBL3137309
PharmGKB
PA166153473
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Venetoclax
AHFS Codes
  • 10:00.00 — Antineoplastic Agents
FDA label
Download (9.7 MB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
0RecruitingTreatmentMalignant Lymphomas / Mantle Cell Lymphoma (MCL)1
1Active Not RecruitingTreatmentAcute Myelogenous Leukaemia (AML) / Leukemia Acute Myeloid Leukemia (AML)1
1Active Not RecruitingTreatmentAcute Myelogenous Leukaemia (AML) / Myelogenous Leukemia / Treatment Naive AML1
1Active Not RecruitingTreatmentChronic Lymphocytic Leukaemia (CLL) / Leukemia, Prolymphocytic / Small Lymphocytic Lymphoma (SLL)1
1Active Not RecruitingTreatmentChronic Lymphocytic Leukaemia (CLL) / Lymphocytic Leukemia, Chronic1
1Active Not RecruitingTreatmentChronic Lymphocytic Leukaemia (CLL) / Non-Hodgkin's Lymphoma (NHL)1
1Active Not RecruitingTreatmentChronic Lymphocytic Leukaemia (CLL) / Small Lymphocytic Lymphoma (SLL)1
1Active Not RecruitingTreatmentLymphocytic Leukemia, Chronic1
1Active Not RecruitingTreatmentNon-Hodgkin's Lymphoma (NHL)2
1Active Not RecruitingTreatmentRelapsed/Refractory Multiple Myeloma1
1CompletedBasic ScienceNon-Hodgkin's Lymphoma (NHL)1
1CompletedTreatmentLupus Erythematosus1
1Not Yet RecruitingTreatmentAcute Lymphoblastic Leukaemias (ALL)1
1Not Yet RecruitingTreatmentBurkitt's Lymphoma / Lymphoma, Large B-Cell, Diffuse (DLBCL) / Malignant Lymphomas / Non-Hodgkin's Lymphoma (NHL)1
1Not Yet RecruitingTreatmentLeukemias1
1Not Yet RecruitingTreatmentLymphoma, Large B-Cell, Diffuse (DLBCL)1
1Not Yet RecruitingTreatmentRelapsed or Refractory Acute Lymphoblastic Leukemia (ALL) / Relapsed or Refractory Acute Myeloid Leukemia (AML) / Relapsed or Refractory Malignancies / Relapsed or Refractory Neuroblastoma / Relapsed or Refractory Non-Hodgkin Lymphoma (NHL) / Relapsed or Refractory Tumors That Expresses B Cell Lymphoma 2 (BCL-2)1
1RecruitingTreatmentAL Amyloidosis1
1RecruitingTreatmentB-Cell Lymphoma, Unclassifiable, With Features Intermediate Between Diffuse Large B-Cell Lymphoma and Burkitt Lymphoma / Grade 1 Follicular Lymphoma / Grade 2 Follicular Lymphoma / Grade 3a Follicular Lymphoma / Recurrent Burkitt Lymphoma / Recurrent Diffuse Large B-Cell Lymphoma / Recurrent Follicular Lymphoma / Recurrent Marginal Zone Lymphoma / Refractory Burkitt Lymphoma / Refractory Diffuse Large B-Cell Lymphoma / Refractory Follicular Lymphoma / Transformed Recurrent Non-Hodgkin Lymphoma1
1RecruitingTreatmentCancer, Advanced / Cancer, Breast / Leukemia Acute Myeloid Leukemia (AML) / Lung Cancer Non-Small Cell Cancer (NSCLC) / Lung Cancer Small Cell Lung Cancer (SCLC) / Multiple Myeloma (MM) / Non-Hodgkin's Lymphoma (NHL) / Prostate Cancer1
1RecruitingTreatmentFollicular Lymphoma (FL)1
1RecruitingTreatmentHigh Grade B-cell Lymphoma / Lymphoma, Large B-Cell, Diffuse (DLBCL)1
1RecruitingTreatmentLeukemia Acute Myeloid Leukemia (AML)1
1RecruitingTreatmentLymphoma, Large B-Cell, Diffuse (DLBCL)1
1RecruitingTreatmentLymphoma, Mantle-Cell / Recurrent Lymphoma, Mantle-Cell1
1RecruitingTreatmentMultiple Myeloma (MM)1
1RecruitingTreatmentMyelodysplastic Syndromes (MDS)1
1RecruitingTreatmentNon-Hodgkin's Lymphoma (NHL)1
1RecruitingTreatmentRefractory Diffuse Large B-Cell Lymphoma / Relapsed Diffuse Large B-Cell Lymphoma1
1RecruitingTreatmentTreatment-Naïve Higher-Risk Myelodysplastic Syndromes (MDS)1
1WithdrawnBasic ScienceNon-Hodgkin's Lymphoma (NHL)1
1WithdrawnBasic ScienceRelapsed/Refractory Non-Hodgkin's Lymphoma1
1WithdrawnTreatmentChronic Lymphocytic Leukaemia (CLL) / Non-Hodgkin's Lymphoma (NHL) / Small Lymphocytic Lymphoma (SLL)1
1, 2Active Not RecruitingTreatmentChronic Lymphocytic Leukaemia (CLL) / Refractory Chronic Lymphocytic Leukemia1
1, 2Active Not RecruitingTreatmentNon-Hodgkin's Lymphoma (NHL)1
1, 2RecruitingTreatmentFollicular Lymphoma (FL) / Lymphoma, Large B-Cell, Diffuse (DLBCL)1
1, 2RecruitingTreatmentLeukemia Acute Myeloid Leukemia (AML)1
1, 2RecruitingTreatmentLeukemia Acute Myeloid Leukemia (AML) / Other Diseases of Blood and Blood-Forming Organs1
1, 2RecruitingTreatmentMantle Cell Lymphoma (MCL)1
1, 2RecruitingTreatmentMultiple Myeloma (MM)1
1, 2RecruitingTreatmentRefractory Follicular Lymphoma / Relapsed Follicular Lymphoma1
2Active Not RecruitingTreatment17 p Deletion / Cancer of the Blood and Bone Marrow / Chronic Lymphocytic Leukaemia (CLL)1
2Active Not RecruitingTreatmentChronic Lymphocytic Leucemia1
2Active Not RecruitingTreatmentChronic Lymphocytic Leukaemia (CLL)1
2Active Not RecruitingTreatmentChronic Lymphocytic Leukaemia (CLL) / Primary Lymphoid Haematopoietic Neoplasms / Small Lymphocytic Lymphoma (SLL)1
2Active Not RecruitingTreatmentChronic Lymphocytic Leukaemia (CLL) / Small Lymphocytic Lymphoma (SLL)1
2Active Not RecruitingTreatmentFollicular Lymphoma (FL) / Relapsed or Refractory Follicular Lymphoma1
2CompletedTreatmentAcute Myelogenous Leukaemia (AML) / Leukemia Acute Myeloid Leukemia (AML)1
2Not Yet RecruitingTreatmentCancer - Multiple Myeloma1
2Not Yet RecruitingTreatmentFollicular Lymphoma (FL) / Lymphoma, Large B-Cell, Diffuse (DLBCL) / Marginal Zone Lymphoma / Mucosa Associated Lymphoid Tissue1
2Not Yet RecruitingTreatmentFollicular Lymphoma (FL) / Non-Hodgkin's Lymphoma Follicular / Non-Hodgkin's Lymphoma, Adult High Grade1
2RecruitingTreatmentChronic Lymphocytic Leukaemia (CLL)1
2RecruitingTreatmentChronic Lymphocytic Leukaemia (CLL) / Chronic Lymphocytic Leumemia / Leukemia Acute Myeloid Leukemia (AML) / Multiple Myeloma (MM) / Non-Hodgkin's Lymphoma (NHL) / Small Lymphocytic Lymphoma (SLL)1
2RecruitingTreatmentChronic Lymphocytic Leukaemia (CLL) / Leukemia, Lymphocytic, Chronic, B-Cell / Small Lymphocytic Lymphoma (SLL)1
2RecruitingTreatmentChronic Lymphocytic Leukaemia (CLL) / Leukemias / Small Lymphocytic Lymphoma (SLL)1
2RecruitingTreatmentLeukemia, Lymphocytic, Chronic1
2RecruitingTreatmentLymphoma, Large B-Cell, Diffuse (DLBCL)1
2RecruitingTreatmentMantle Cell Lymphoma (MCL)1
2RecruitingTreatmentRecurrent Chronic Lymphocytic Leukemia / Recurrent Small Lymphocytic Lymphoma / Refractory Chronic Lymphocytic Leukemia / Refractory Small Lymphocytic Lymphoma1
2RecruitingTreatmentRelapsed Or Refractory Multiple Myeloma1
2RecruitingTreatmentRelapsed/Refractory Multiple Myeloma1
2RecruitingTreatmentRichter's Syndrome1
2RecruitingTreatmentWaldenstrom's Macroglobulinemia (WM)1
3Active Not RecruitingTreatmentChronic Lymphocytic Leukaemia (CLL)1
3Active Not RecruitingTreatmentLymphocytic Leukemia, Chronic1
3Active Not RecruitingTreatmentRelapsed/Refractory Multiple Myeloma1
3RecruitingTreatmentChronic Lymphocytic Leukaemia (CLL)3
3RecruitingTreatmentLeukemia Acute Myeloid Leukemia (AML)2
3RecruitingTreatmentLymphoma, Mantle-Cell1
Not AvailableAvailableNot AvailableChronic Lymphocytic Leukaemia (CLL) / Leukemia Acute Myeloid Leukemia (AML) / Multiple Myeloma (MM) / Non-Hodgkin's Lymphoma (NHL)1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
Kit
Kit; tabletOral
TabletOral10 mg
TabletOral100 mg
TabletOral50 mg
Tablet, film coatedOral10 mg/1
Tablet, film coatedOral100 mg/1
Tablet, film coatedOral50 mg/1
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US9174982No2010-05-262030-05-26Us
US8546399No2011-06-272031-06-27Us

Properties

State
Solid
Experimental Properties
Not Available
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

Taxonomy

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
Phenylpiperazine / N-arylpiperazine / Diaryl ether / Aminobenzenesulfonamide / Benzenesulfonamide / Aminobenzoic acid or derivatives / Benzenesulfonyl group / Pyrrolopyridine / Nitrobenzene / Benzoic acid or derivatives
show 52 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
Not Available

Targets

Kind
Protein
Organism
Human
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]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Substrate
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]

Transporters

Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Substrate
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]
Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Substrate
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. 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]

Drug created on April 18, 2016 10:22 / Updated on November 19, 2017 20:33