Identification

Name
Venetoclax
Accession Number
DB11581
Type
Small Molecule
Groups
Approved, Investigational
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
VenclextaTablet, film coated100 mg/1OralAbbVie Inc.2016-04-11Not applicableUs
VenclextaTablet100 mgOralAbbvie2016-10-31Not applicableCanada
VenclextaTablet, film coated50 mg/1OralAbbVie Inc.2016-04-11Not applicableUs
VenclextaTablet50 mgOralAbbvie2016-10-31Not applicableCanada
VenclextaTablet, film coated10 mg/1OralAbbVie Inc.2016-04-11Not applicableUs
VenclextaTablet10 mgOralAbbvie2016-10-31Not applicableCanada
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
VenclextaVenetoclax (10 mg/1) + Venetoclax (50 mg/1) + Venetoclax (100 mg/1) + Venetoclax (100 mg/1)KitAbbVie Inc.2016-04-11Not applicableUs
VenclextaVenetoclax (10 mg) + Venetoclax (50 mg) + Venetoclax (100 mg)Kit; TabletOralAbbvie2016-10-31Not applicableCanada
VenclextaVenetoclax (10 mg/1) + Venetoclax (50 mg/1) + Venetoclax (100 mg/1) + Venetoclax (100 mg/1)KitAbbVie Inc.2016-04-11Not applicableUs
VenclextaVenetoclax (10 mg) + Venetoclax (50 mg) + Venetoclax (100 mg)Kit; TabletOralAbbvie2016-10-31Not applicableCanada
VenclextaVenetoclax (10 mg/1) + Venetoclax (50 mg/1) + Venetoclax (100 mg/1) + Venetoclax (100 mg/1)KitAbbVie Inc.2016-04-11Not applicableUs
VenclextaVenetoclax (10 mg) + Venetoclax (50 mg) + Venetoclax (100 mg)Kit; TabletOralAbbvie2016-10-31Not applicableCanada
VenclextaVenetoclax (10 mg/1) + Venetoclax (50 mg/1) + Venetoclax (100 mg/1) + Venetoclax (100 mg/1)KitAbbVie Inc.2016-04-11Not applicableUs
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.

Associated Conditions
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

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
DrugInteraction
(R)-warfarinThe metabolism of Venetoclax can be decreased when combined with (R)-warfarin.
(S)-WarfarinThe metabolism of (S)-Warfarin can be decreased when combined with Venetoclax.
3,5-diiodothyropropionic acidThe metabolism of 3,5-diiodothyropropionic acid can be decreased when combined with Venetoclax.
4-hydroxycoumarinThe metabolism of 4-hydroxycoumarin can be decreased when combined with Venetoclax.
5-androstenedioneThe metabolism of Venetoclax can be decreased when combined with 5-androstenedione.
6-Deoxyerythronolide BThe metabolism of Venetoclax can be decreased when combined with 6-Deoxyerythronolide B.
6-O-benzylguanineThe metabolism of 6-O-benzylguanine can be decreased when combined with Venetoclax.
AbemaciclibThe serum concentration of Abemaciclib can be increased when it is combined with Venetoclax.
AbirateroneThe metabolism of Venetoclax can be decreased when combined with Abiraterone.
AcalabrutinibThe metabolism of Venetoclax can be decreased when combined with Acalabrutinib.
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 RecruitingTreatmentChronic Lymphocytic Leukaemia (CLL)2
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 RecruitingTreatmentLymphoma, Large B-Cell, Diffuse (DLBCL)1
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 RecruitingBasic ScienceMalignancies, Hematologic1
1Not Yet RecruitingTreatmentChronic Lymphocytic Leukaemia (CLL) / Chronic Lymphocytic Leukemia (CLL) - Refractory / Relapsed Chronic Lymphocytic Leukemia1
1Not Yet RecruitingTreatmentLeukemia Acute Myeloid Leukemia (AML)2
1Not Yet RecruitingTreatmentMantle Cell Lymphoma (MCL)1
1Not Yet RecruitingTreatmentNon-Hodgkin's Lymphoma (NHL)1
1RecruitingOtherFollicular Lymphoma (FL) / Lymphoma, Large B-Cell, Diffuse (DLBCL) / Non-Hodgkin's Lymphoma (NHL)1
1RecruitingTreatmentAL Amyloidosis1
1RecruitingTreatmentAcute Lymphoblastic Leukaemias (ALL) / Leukemia Acute Myeloid Leukemia (AML) / Malignancies / Neuroblastomas / Non-Hodgkin's Lymphoma (NHL) / Relapsed 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
1RecruitingTreatmentAcute Lymphoblastic Leukaemias (ALL) / Lymphoma, Lymphoblastic1
1RecruitingTreatmentAdvanced Solid Tumors Cancer / Malignancies, Hematologic / Tumors, Solid1
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
1RecruitingTreatmentBlastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN)1
1RecruitingTreatmentBurkitt's Lymphoma / Lymphoma, Large B-Cell, Diffuse (DLBCL) / Malignant Lymphomas / Non-Hodgkin's Lymphoma (NHL)1
1RecruitingTreatmentCancer - Acute Myeloid Leukemia / Leukemia Acute Myeloid Leukemia (AML)1
1RecruitingTreatmentCancer, Advanced / Cancer, Breast / Leukemia Acute Myeloid Leukemia (AML) / Lung Cancer Non-Small Cell Cancer (NSCLC) / Lung Cancer Small Cell Lung Cancer (SCLC) / Malignancies / Multiple Myeloma (MM) / Non-Hodgkin's Lymphoma (NHL) / Prostate Cancer1
1RecruitingTreatmentChronic Lymphocytic Leukaemia (CLL) / Leukemia, Prolymphocytic / Small Lymphocytic Lymphoma (SLL)1
1RecruitingTreatmentChronic Lymphocytic Leukaemia (CLL) / Small Lymphocytic Lymphoma (SLL)1
1RecruitingTreatmentChronic Myelomonocytic Leukemia (CMML) / Hematopoietic Stem Cell Transplant (HSCT) / Leukemia Acute Myeloid Leukemia (AML) / MDS/Myeloproliferative Neoplasm-unclassifiable (MDS/MPN-unclassifiable) / Myelodysplastic Syndromes (MDS)1
1RecruitingTreatmentFollicular Lymphoma (FL)1
1RecruitingTreatmentHigh Grade B-cell Lymphoma / Lymphoma, Large B-Cell, Diffuse (DLBCL)1
1RecruitingTreatmentLeukemia Acute Myeloid Leukemia (AML)3
1RecruitingTreatmentLeukemias1
1RecruitingTreatmentLymphoma, Large B-Cell, Diffuse (DLBCL)1
1RecruitingTreatmentMantle Cell Lymphoma (MCL) / Recurrent Lymphoma, Mantle-Cell1
1RecruitingTreatmentMultiple Myeloma (MM)1
1RecruitingTreatmentMyelodysplastic Syndromes (MDS)1
1RecruitingTreatmentMyelodysplastic Syndromes (MDS) / Treatment-Naïve Higher-Risk Myelodysplastic Syndromes (MDS)1
1RecruitingTreatmentNon-Hodgkin's Lymphoma (NHL)1
1RecruitingTreatmentRefractory Diffuse Large B Cell Lymphoma / Relapsed, Diffuse Large B-cell Lymphoma1
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
1WithdrawnTreatmentLeukemia, Lymphocytic, Chronic, B-Cell1
1, 2Active Not RecruitingTreatmentAcute Myelogenous Leukaemia (AML) / Leukemia Acute Myeloid Leukemia (AML)1
1, 2Active Not RecruitingTreatmentAcute Myelogenous Leukaemia (AML) / Myelogenous Leukemia / Treatment Naive AML1
1, 2Active Not RecruitingTreatmentChronic Lymphocytic Leukaemia (CLL) / Chronic Lymphocytic Leukemia (CLL) - Refractory1
1, 2Active Not RecruitingTreatmentChronic Lymphocytic Leukaemia (CLL) / Chronic Lymphocytic Leumemia / Chronic Lymphocytic Leumemia (CLL) / Leukemia Acute Myeloid Leukemia (AML) / Multiple Myeloma (MM) / Non-Hodgkin's Lymphoma (NHL) / Small Lymphocytic Lymphoma (SLL)1
1, 2Active Not RecruitingTreatmentNon-Hodgkin's Lymphoma (NHL)1
1, 2Not Yet RecruitingTreatmentRecurrent Plasma Cell Myeloma / Refractory Plasma Cell Myeloma1
1, 2Not Yet RecruitingTreatmentRelapsed Non Hodgkin Lymphoma1
1, 2RecruitingTreatmentAdvanced Hematologic Malignancies / Leukemia Acute Myeloid Leukemia (AML) / Other Diseases of Blood and Blood-Forming Organs1
1, 2RecruitingTreatmentB Acute Lymphoblastic Leukemia / Lymphoblasts 5 Percent or More of Bone Marrow Nucleated Cells / Recurrent Adult Acute Lymphoblastic Leukemia / Recurrent Childhood Acute Lymphoblastic Leukemia / Refractory Acute Lymphoblastic Leukemia / T Acute Lymphoblastic Leukemia1
1, 2RecruitingTreatmentChronic Lymphocytic Leukaemia (CLL)2
1, 2RecruitingTreatmentFollicular Lymphoma (FL) / Lymphoma, Large B-Cell, Diffuse (DLBCL)1
1, 2RecruitingTreatmentHematopoietic Cell Transplantation Recipient / Recurrent Diffuse Large B-Cell Lymphoma / Recurrent Grade 1 Follicular Lymphoma / Recurrent Grade 2 Follicular Lymphoma / Recurrent Grade 3 Follicular Lymphoma / Recurrent Marginal Zone Lymphoma / Recurrent Non-Hodgkin Lymphoma / Refractory Diffuse Large B Cell Lymphoma / Refractory Follicular Lymphoma / Refractory Marginal Zone Lymphoma / Refractory Non-Hodgkin's lymphoma / Refractory Transformed Indolent Non-Hodgkin Lymphoma1
1, 2RecruitingTreatmentLeukemia Acute Myeloid Leukemia (AML)1
1, 2RecruitingTreatmentLeukemia Acute Myeloid Leukemia (AML) / Other Diseases of Blood and Blood-Forming Organs1
1, 2RecruitingTreatmentLeukemias1
1, 2RecruitingTreatmentMantle Cell Lymphoma (MCL)1
1, 2RecruitingTreatmentMultiple Myeloma (MM)1
1, 2RecruitingTreatmentMultiple Myeloma (MM) / Relapsed/Refractory Multiple Myeloma1
1, 2RecruitingTreatmentRecurrent Plasma Cell Myeloma / T(11;14)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) / Leukemia, Lymphocytic, Chronic, B-Cell / Small Lymphocytic Lymphoma (SLL)1
2Active Not RecruitingTreatmentChronic Lymphocytic Leukaemia (CLL) / Small Lymphocytic Lymphoma (SLL)1
2Active Not RecruitingTreatmentWaldenström's Macroglobulinemia (WM)1
2CompletedTreatmentAcute Myelogenous Leukaemia (AML) / Leukemia Acute Myeloid Leukemia (AML)1
2CompletedTreatmentFollicular Lymphoma (FL) / Relapsed or Refractory Follicular Lymphoma1
2Not Yet RecruitingTreatmentCD20 Positive / Mantle Cell Lymphoma (MCL)1
2Not Yet RecruitingTreatmentChronic Lymphocytic Leukaemia (CLL)1
2Not Yet RecruitingTreatmentChronic Lymphocytic Leukaemia (CLL) / Ibrutinib Resistance1
2Not Yet RecruitingTreatmentChronic Lymphocytic Leukaemia (CLL) / Leukemias / Relapsed or Refractory Chronic Lymphocytic Leukemia (CLL)1
2Not Yet RecruitingTreatmentChronic Myeloid Leukemia (CML)1
2Not Yet RecruitingTreatmentLeukemia Acute Myeloid Leukemia (AML)2
2Not Yet RecruitingTreatmentMantle Cell Lymphoma (MCL)1
2Not Yet RecruitingTreatmentRecurrent Cutaneous T-cell lymphoma / Refractory T-Cell Lymphoma1
2RecruitingTreatmentCancer - Multiple Myeloma / Multiple Myeloma (MM)1
2RecruitingTreatmentChronic Lymphocytic Leukaemia (CLL)4
2RecruitingTreatmentChronic Lymphocytic Leukaemia (CLL) / Leukemias / Small Lymphocytic Lymphoma (SLL)1
2RecruitingTreatmentChronic Lymphocytic Leukaemia (CLL) / Primary Lymphoid Haematopoietic Neoplasms / Small Lymphocytic Lymphoma (SLL)1
2RecruitingTreatmentChronic Lymphocytic Leukemia (CLL) - Refractory / Chronic, recurrent Lymphocytic Leukemia / Recurrent Small Lymphocytic Lymphoma / Refractory Small Lymphocytic Lymphoma1
2RecruitingTreatmentEstrogen Receptor-positive (ER+)/Human Epidermal Growth Factor Receptor (HER2)-Negative Locally Advanced or Metastatic Breast Cancer1
2RecruitingTreatmentFollicular Lymphoma (FL) / Lymphoma, Large B-Cell, Diffuse (DLBCL) / Marginal Zone Lymphoma / Mucosa Associated Lymphoid Tissue1
2RecruitingTreatmentLeukemia Acute Myeloid Leukemia (AML)2
2RecruitingTreatmentLeukemia Acute Myeloid Leukemia (AML) / Myelodysplastic Syndrome / Other Diseases of Blood and Blood-Forming Organs1
2RecruitingTreatmentLymphoma, Large B-Cell, Diffuse (DLBCL)1
2RecruitingTreatmentMantle Cell Lymphoma (MCL)1
2RecruitingTreatmentMultiple Myeloma (MM)1
2RecruitingTreatmentMultiple Myeloma (MM) / Relapsed Or Refractory Multiple Myeloma1
2RecruitingTreatmentRecurrent Mature T- and NK-Cell Non-Hodgkin Lymphoma / Refractory Mature T-Cell and NK-Cell Non-Hodgkin Lymphoma1
2RecruitingTreatmentAcute, recurrent Myeloid Leukemia / Refractory Acute Myeloid Leukemia / Untreated Adult Acute Myeloid Leukemia1
2RecruitingTreatmentRichter's Syndrome1
2RecruitingTreatmentChronic Chronic myelogenous leukemia1
2SuspendedTreatmentFollicular Lymphoma (FL) / Non-Hodgkin's Lymphoma Follicular / Non-Hodgkin's Lymphoma, Adult High Grade1
3Active Not RecruitingTreatmentChronic Lymphocytic Leukaemia (CLL)4
3Active Not RecruitingTreatmentRelapsed/Refractory Multiple Myeloma1
3Not Yet RecruitingTreatmentCCND1 Negative / Chronic Lymphocytic Leukaemia (CLL) / Small Lymphocytic Lymphoma (SLL) / T(11;14) Negative1
3RecruitingTreatmentCancer - Chronic Lymphocytic Leukemia / Chronic Lymphocytic Leukaemia (CLL) / Small Lymphocytic Lymphoma (SLL)1
3RecruitingTreatmentChronic Lymphocytic Leukaemia (CLL)1
3RecruitingTreatmentLeukemia Acute Myeloid Leukemia (AML)2
3RecruitingTreatmentLeukemia, Lymphocytic, Chronic, B-Cell1
3RecruitingTreatmentMantle Cell Lymphoma (MCL)1
3RecruitingTreatmentMultiple Myeloma (MM)1
Not AvailableAvailableNot AvailableChronic Lymphocytic Leukaemia (CLL) / Leukemia Acute Myeloid Leukemia (AML) / Multiple Myeloma (MM) / Non-Hodgkin's Lymphoma (NHL)1
Not AvailableRecruitingNot AvailableLeukemia Acute Myeloid Leukemia (AML)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)
US9174982No2015-11-032030-05-26Us
US8546399No2013-10-012031-06-27Us

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 17, 2018 04:48