Identification
NameVenetoclax
Accession NumberDB11581
TypeSmall Molecule
GroupsApproved
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
Product Ingredients Not Available
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
VenclextaTablet, film coated10 mg/1OralAbbvie2016-04-11Not applicableUs
VenclextaKitAbbvie2016-04-11Not applicableUs
VenclextaTablet100 mgOralAbbvie2016-10-31Not applicableCanada
VenclextaTablet, film coated50 mg/1OralAbbvie2016-04-11Not applicableUs
VenclextaTablet10 mgOralAbbvie2016-10-31Not applicableCanada
VenclextaTablet, film coated100 mg/1OralAbbvie2016-04-11Not applicableUs
VenclextaTablet50 mgOralAbbvie2016-10-31Not applicableCanada
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International BrandsNot Available
Brand mixtures
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
VenclextaKit; TabletOralAbbvie2016-10-31Not applicableCanada
Categories
UNIIN54AIC43PW
CAS number1257044-40-8
WeightAverage: 868.45
Monoisotopic: 867.3180959
Chemical FormulaC45H50ClN7O7S
InChI KeyLQBVNQSMGBZMKD-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.

TargetKindPharmacological actionActionsOrganismUniProt ID
Apoptosis regulator Bcl-2Proteinyes
inhibitor
HumanP10415 details
Related Articles
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

SubstrateEnzymesProduct
Venetoclax
M27 Details
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

ClearanceNot 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 organismsNot Available
PathwaysNot Available
Pharmacogenomic Effects/ADRs Not Available
Interactions
Drug Interactions
DrugInteractionDrug group
AcetaminophenThe serum concentration of Venetoclax can be increased when it is combined with Acetaminophen.Approved
AfatinibThe serum concentration of Venetoclax can be increased when it is combined with Afatinib.Approved
AlbendazoleThe serum concentration of Venetoclax can be increased when it is combined with Albendazole.Approved, Vet Approved
AldosteroneThe serum concentration of Venetoclax can be decreased when it is combined with Aldosterone.Experimental
AlectinibThe serum concentration of Venetoclax can be increased when it is combined with Alectinib.Approved
AlfentanilThe serum concentration of Venetoclax can be increased when it is combined with Alfentanil.Approved, Illicit
AmantadineThe serum concentration of Venetoclax can be increased when it is combined with Amantadine.Approved
Aminohippuric acidThe serum concentration of Venetoclax can be increased when it is combined with Aminohippuric acid.Approved
AmiodaroneThe metabolism of Venetoclax can be decreased when combined with Amiodarone.Approved, Investigational
AmitriptylineThe serum concentration of Venetoclax can be increased when it is combined with Amitriptyline.Approved
AmlodipineThe serum concentration of Venetoclax can be increased when it is combined with Amlodipine.Approved
AmprenavirThe serum concentration of Venetoclax can be decreased when it is combined with Amprenavir.Approved
AmsacrineThe serum concentration of Venetoclax can be increased when it is combined with Amsacrine.Approved
AprepitantThe serum concentration of Venetoclax can be increased when it is combined with Aprepitant.Approved, Investigational
AstemizoleThe serum concentration of Venetoclax can be increased when it is combined with Astemizole.Approved, Withdrawn
AtazanavirThe metabolism of Venetoclax can be decreased when combined with Atazanavir.Approved, Investigational
AtenololThe serum concentration of Venetoclax can be increased when it is combined with Atenolol.Approved
AtomoxetineThe metabolism of Venetoclax can be decreased when combined with Atomoxetine.Approved
AtorvastatinThe serum concentration of Venetoclax can be increased when it is combined with Atorvastatin.Approved
AzelastineThe serum concentration of Venetoclax can be increased when it is combined with Azelastine.Approved
AzithromycinThe serum concentration of Venetoclax can be increased when it is combined with Azithromycin.Approved
BenzocaineThe serum concentration of Venetoclax can be increased when it is combined with Benzocaine.Approved
BepridilThe serum concentration of Venetoclax can be increased when it is combined with Bepridil.Approved, Withdrawn
BexaroteneThe serum concentration of Venetoclax can be decreased when it is combined with Bexarotene.Approved, Investigational
BiperidenThe serum concentration of Venetoclax can be increased when it is combined with Biperiden.Approved
BoceprevirThe metabolism of Venetoclax can be decreased when combined with Boceprevir.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
BosutinibThe serum concentration of Venetoclax can be increased when it is combined with Bosutinib.Approved
BromocriptineThe serum concentration of Venetoclax can be increased when it is combined with Bromocriptine.Approved, Investigational
BuprenorphineThe serum concentration of Venetoclax can be increased when it is combined with Buprenorphine.Approved, Illicit, Investigational, Vet Approved
BuspironeThe serum concentration of Venetoclax can be increased when it is combined with Buspirone.Approved, Investigational
CabazitaxelThe serum concentration of Venetoclax can be increased when it is combined with Cabazitaxel.Approved
CaffeineThe serum concentration of Venetoclax can be increased when it is combined with Caffeine.Approved
CanagliflozinThe serum concentration of Venetoclax can be increased when it is combined with Canagliflozin.Approved
CandesartanThe serum concentration of Venetoclax can be increased when it is combined with Candesartan.Approved
CaptoprilThe serum concentration of Venetoclax can be increased when it is combined with Captopril.Approved
CarbamazepineThe metabolism of Venetoclax can be increased when combined with Carbamazepine.Approved, Investigational
CarvedilolThe serum concentration of Venetoclax can be increased when it is combined with Carvedilol.Approved, Investigational
CaspofunginThe serum concentration of Venetoclax can be increased when it is combined with Caspofungin.Approved
CeritinibThe serum concentration of Venetoclax can be increased when it is combined with Ceritinib.Approved
ChloroquineThe serum concentration of Venetoclax can be increased when it is combined with Chloroquine.Approved, Vet Approved
ChlorpromazineThe serum concentration of Venetoclax can be increased when it is combined with Chlorpromazine.Approved, Vet Approved
ChlorpropamideThe serum concentration of Venetoclax can be increased when it is combined with Chlorpropamide.Approved
ChlorprothixeneThe serum concentration of Venetoclax can be increased when it is combined with Chlorprothixene.Approved, Withdrawn
CholesterolThe serum concentration of Venetoclax can be increased when it is combined with Cholesterol.Experimental
Cholic AcidThe serum concentration of Venetoclax can be decreased when it is combined with Cholic Acid.Approved
CilazaprilThe serum concentration of Venetoclax can be increased when it is combined with Cilazapril.Approved
CimetidineThe serum concentration of Venetoclax can be decreased when it is combined with Cimetidine.Approved
CiprofloxacinThe serum concentration of Venetoclax can be increased when it is combined with Ciprofloxacin.Approved, Investigational
CitalopramThe serum concentration of Venetoclax can be increased when it is combined with Citalopram.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
ClofazimineThe serum concentration of Venetoclax can be increased when it is combined with Clofazimine.Approved, Investigational
ClomipramineThe serum concentration of Venetoclax can be increased when it is combined with Clomipramine.Approved, Vet 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
ColchicineThe serum concentration of Venetoclax can be increased when it is combined with Colchicine.Approved
ColforsinThe serum concentration of Venetoclax can be increased when it is combined with Colforsin.Experimental
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
CyclophosphamideThe serum concentration of Venetoclax can be increased when it is combined with Cyclophosphamide.Approved, Investigational
CyclosporineThe metabolism of Venetoclax can be decreased when combined with Cyclosporine.Approved, Investigational, Vet Approved
DabrafenibThe serum concentration of Venetoclax can be decreased when it is combined with Dabrafenib.Approved
DaclatasvirThe serum concentration of Venetoclax can be increased when it is combined with Daclatasvir.Approved
DactinomycinThe serum concentration of Venetoclax can be increased when it is combined with Dactinomycin.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
DaunorubicinThe serum concentration of Venetoclax can be decreased when it is combined with Daunorubicin.Approved
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
DesipramineThe serum concentration of Venetoclax can be increased when it is combined with Desipramine.Approved
DesloratadineThe serum concentration of Venetoclax can be increased when it is combined with Desloratadine.Approved, Investigational
DexamethasoneThe serum concentration of Venetoclax can be decreased when it is combined with Dexamethasone.Approved, Investigational, Vet Approved
DextromethorphanThe serum concentration of Venetoclax can be increased when it is combined with Dextromethorphan.Approved
DiclofenacThe serum concentration of Venetoclax can be increased when it is combined with Diclofenac.Approved, Vet Approved
DigoxinThe serum concentration of Venetoclax can be decreased when it is combined with Digoxin.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
DipyridamoleThe serum concentration of Venetoclax can be increased when it is combined with Dipyridamole.Approved
DoxazosinThe serum concentration of Venetoclax can be increased when it is combined with Doxazosin.Approved
DoxepinThe serum concentration of Venetoclax can be increased when it is combined with Doxepin.Approved
DoxorubicinThe serum concentration of Venetoclax can be decreased when it is combined with Doxorubicin.Approved, Investigational
DoxycyclineThe metabolism of Venetoclax can be decreased when combined with Doxycycline.Approved, Investigational, Vet Approved
DronabinolThe serum concentration of Venetoclax can be increased when it is combined with Dronabinol.Approved, Illicit
DronedaroneThe metabolism of Venetoclax can be decreased when combined with Dronedarone.Approved
EfavirenzThe serum concentration of Venetoclax can be decreased when it is combined with Efavirenz.Approved, Investigational
ElbasvirThe serum concentration of Venetoclax can be increased when it is combined with Elbasvir.Approved
EltrombopagThe serum concentration of Venetoclax can be increased when it is combined with Eltrombopag.Approved
EnalaprilThe serum concentration of Venetoclax can be increased when it is combined with Enalapril.Approved, Vet Approved
EnzalutamideThe serum concentration of Venetoclax can be decreased when it is combined with Enzalutamide.Approved
ErgonovineThe serum concentration of Venetoclax can be increased when it is combined with Ergonovine.Approved
ErgotamineThe serum concentration of Venetoclax can be increased when it is combined with Ergotamine.Approved
ErythromycinThe metabolism of Venetoclax can be decreased when combined with Erythromycin.Approved, Vet Approved
Eslicarbazepine acetateThe serum concentration of Venetoclax can be decreased when it is combined with Eslicarbazepine acetate.Approved
EstramustineThe serum concentration of Venetoclax can be increased when it is combined with Estramustine.Approved
EstriolThe serum concentration of Venetoclax can be decreased when it is combined with Estriol.Approved, Vet Approved
EstroneThe serum concentration of Venetoclax can be decreased when it is combined with Estrone.Approved
EtoposideThe serum concentration of Venetoclax can be increased when it is combined with Etoposide.Approved
EtravirineThe serum concentration of Venetoclax can be decreased when it is combined with Etravirine.Approved
FelodipineThe serum concentration of Venetoclax can be increased when it is combined with Felodipine.Approved, Investigational
FentanylThe serum concentration of Venetoclax can be increased when it is combined with Fentanyl.Approved, Illicit, Investigational, Vet Approved
FexofenadineThe serum concentration of Venetoclax can be increased when it is combined with Fexofenadine.Approved
FidaxomicinThe serum concentration of Venetoclax can be increased when it is combined with Fidaxomicin.Approved
FluconazoleThe metabolism of Venetoclax can be decreased when combined with Fluconazole.Approved
FluoxetineThe serum concentration of Venetoclax can be increased when it is combined with Fluoxetine.Approved, Vet Approved
FlupentixolThe serum concentration of Venetoclax can be increased when it is combined with Flupentixol.Approved, Withdrawn
FluphenazineThe serum concentration of Venetoclax can be increased when it is combined with Fluphenazine.Approved
FlurazepamThe serum concentration of Venetoclax can be increased when it is combined with Flurazepam.Approved, Illicit
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
GefitinibThe serum concentration of Venetoclax can be increased when it is combined with Gefitinib.Approved, Investigational
GenisteinThe serum concentration of Venetoclax can be increased when it is combined with Genistein.Investigational
GlyburideThe serum concentration of Venetoclax can be increased when it is combined with Glyburide.Approved
Gramicidin DThe serum concentration of Venetoclax can be increased when it is combined with Gramicidin D.Approved
GrepafloxacinThe serum concentration of Venetoclax can be increased when it is combined with Grepafloxacin.Withdrawn
HaloperidolThe serum concentration of Venetoclax can be increased when it is combined with Haloperidol.Approved
HydrocortisoneThe serum concentration of Venetoclax can be increased when it is combined with Hydrocortisone.Approved, Vet Approved
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
ImipramineThe serum concentration of Venetoclax can be increased when it is combined with Imipramine.Approved
IndinavirThe metabolism of Venetoclax can be decreased when combined with Indinavir.Approved
IndomethacinThe serum concentration of Venetoclax can be increased when it is combined with Indomethacin.Approved, Investigational
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
IvermectinThe serum concentration of Venetoclax can be increased when it is combined with Ivermectin.Approved, Vet Approved
KetamineThe serum concentration of Venetoclax can be increased when it is combined with Ketamine.Approved, Vet Approved
KetoconazoleThe metabolism of Venetoclax can be decreased when combined with Ketoconazole.Approved, Investigational
LansoprazoleThe serum concentration of Venetoclax can be increased when it is combined with Lansoprazole.Approved, Investigational
LapatinibThe serum concentration of Venetoclax can be increased when it is combined with Lapatinib.Approved, Investigational
LevofloxacinThe serum concentration of Venetoclax can be increased when it is combined with Levofloxacin.Approved, Investigational
LevothyroxineThe serum concentration of Venetoclax can be decreased when it is combined with Levothyroxine.Approved
LidocaineThe serum concentration of Venetoclax can be increased when it is combined with Lidocaine.Approved, Vet Approved
LiothyronineThe serum concentration of Venetoclax can be decreased when it is combined with Liothyronine.Approved, Vet Approved
LiotrixThe serum concentration of Venetoclax can be decreased when it is combined with Liotrix.Approved
LisinoprilThe serum concentration of Venetoclax can be increased when it is combined with Lisinopril.Approved, Investigational
LomitapideThe serum concentration of Venetoclax can be increased when it is combined with Lomitapide.Approved
LoperamideThe serum concentration of Venetoclax can be increased when it is combined with Loperamide.Approved
LopinavirThe metabolism of Venetoclax can be decreased when combined with Lopinavir.Approved
LoratadineThe serum concentration of Venetoclax can be increased when it is combined with Loratadine.Approved
LosartanThe serum concentration of Venetoclax can be increased when it is combined with Losartan.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
MaprotilineThe serum concentration of Venetoclax can be increased when it is combined with Maprotiline.Approved
MebendazoleThe serum concentration of Venetoclax can be increased when it is combined with Mebendazole.Approved, Vet Approved
MefloquineThe serum concentration of Venetoclax can be increased when it is combined with Mefloquine.Approved
Megestrol acetateThe serum concentration of Venetoclax can be increased when it is combined with Megestrol acetate.Approved, Vet Approved
MeprobamateThe serum concentration of Venetoclax can be increased when it is combined with Meprobamate.Approved, Illicit
MethadoneThe serum concentration of Venetoclax can be increased when it is combined with Methadone.Approved
MetoprololThe serum concentration of Venetoclax can be increased when it is combined with Metoprolol.Approved, Investigational
MibefradilThe serum concentration of Venetoclax can be increased when it is combined with Mibefradil.Withdrawn
MiconazoleThe serum concentration of Venetoclax can be increased when it is combined with Miconazole.Approved, Investigational, Vet Approved
MidazolamThe serum concentration of Venetoclax can be decreased when it is combined with Midazolam.Approved, Illicit
MifepristoneThe serum concentration of Venetoclax can be increased when it is combined with Mifepristone.Approved, Investigational
MitomycinThe serum concentration of Venetoclax can be increased when it is combined with Mitomycin.Approved
MitotaneThe serum concentration of Venetoclax can be decreased when it is combined with Mitotane.Approved
MitoxantroneThe serum concentration of Venetoclax can be decreased when it is combined with Mitoxantrone.Approved, Investigational
ModafinilThe serum concentration of Venetoclax can be decreased when it is combined with Modafinil.Approved, Investigational
MorphineThe serum concentration of Venetoclax can be increased when it is combined with Morphine.Approved, Investigational
NafcillinThe serum concentration of Venetoclax can be decreased when it is combined with Nafcillin.Approved
NaltrexoneThe serum concentration of Venetoclax can be increased when it is combined with Naltrexone.Approved, Investigational, Vet Approved
NaringeninThe serum concentration of Venetoclax can be increased when it is combined with Naringenin.Experimental
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
NeostigmineThe serum concentration of Venetoclax can be increased when it is combined with Neostigmine.Approved, Vet 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
NicardipineThe serum concentration of Venetoclax can be increased when it is combined with Nicardipine.Approved
NifedipineThe serum concentration of Venetoclax can be decreased when it is combined with Nifedipine.Approved
NilotinibThe metabolism of Venetoclax can be decreased when combined with Nilotinib.Approved, Investigational
NisoldipineThe serum concentration of Venetoclax can be increased when it is combined with Nisoldipine.Approved
NitrazepamThe serum concentration of Venetoclax can be increased when it is combined with Nitrazepam.Approved
NitrendipineThe serum concentration of Venetoclax can be increased when it is combined with Nitrendipine.Approved
NorethisteroneThe serum concentration of Venetoclax can be decreased when it is combined with Norethisterone.Approved
OlaparibThe metabolism of Venetoclax can be decreased when combined with Olaparib.Approved
OmeprazoleThe serum concentration of Venetoclax can be increased when it is combined with Omeprazole.Approved, Investigational, Vet Approved
OsimertinibThe serum concentration of Venetoclax can be increased when it is combined with Osimertinib.Approved
P-NitrophenolThe serum concentration of Venetoclax can be increased when it is combined with P-Nitrophenol.Experimental
PaclitaxelThe serum concentration of Venetoclax can be increased when it is combined with Paclitaxel.Approved, Vet Approved
PalbociclibThe serum concentration of Venetoclax can be increased when it is combined with Palbociclib.Approved
Palmitic AcidThe serum concentration of Venetoclax can be increased when it is combined with Palmitic Acid.Experimental
PantoprazoleThe serum concentration of Venetoclax can be increased when it is combined with Pantoprazole.Approved
ParoxetineThe serum concentration of Venetoclax can be increased when it is combined with Paroxetine.Approved, Investigational
PentobarbitalThe metabolism of Venetoclax can be increased when combined with Pentobarbital.Approved, Vet Approved
PerindoprilThe serum concentration of Venetoclax can be increased when it is combined with Perindopril.Approved
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
PimozideThe serum concentration of Venetoclax can be increased when it is combined with Pimozide.Approved
Platelet Activating FactorThe serum concentration of Venetoclax can be decreased when it is combined with Platelet Activating Factor.Experimental
PonatinibThe serum concentration of Venetoclax can be increased when it is combined with Ponatinib.Approved
PosaconazoleThe metabolism of Venetoclax can be decreased when combined with Posaconazole.Approved, Investigational, Vet Approved
PravastatinThe serum concentration of Venetoclax can be increased when it is combined with Pravastatin.Approved
PrazosinThe serum concentration of Venetoclax can be increased when it is combined with Prazosin.Approved
PrednisoneThe serum concentration of Venetoclax can be increased when it is combined with Prednisone.Approved, Vet Approved
PrimidoneThe metabolism of Venetoclax can be increased when combined with Primidone.Approved, Vet Approved
ProbenecidThe serum concentration of Venetoclax can be increased when it is combined with Probenecid.Approved
ProgesteroneThe serum concentration of Venetoclax can be decreased when it is combined with Progesterone.Approved, Vet Approved
PromethazineThe serum concentration of Venetoclax can be increased when it is combined with Promethazine.Approved
PropafenoneThe serum concentration of Venetoclax can be increased when it is combined with Propafenone.Approved
PropranololThe serum concentration of Venetoclax can be increased when it is combined with Propranolol.Approved, Investigational
ProtriptylineThe serum concentration of Venetoclax can be increased when it is combined with Protriptyline.Approved
QuercetinThe serum concentration of Venetoclax can be increased when it is combined with Quercetin.Experimental
QuinacrineThe serum concentration of Venetoclax can be increased when it is combined with Quinacrine.Approved
QuinidineThe serum concentration of Venetoclax can be increased when it is combined with Quinidine.Approved
QuinineThe serum concentration of Venetoclax can be increased when it is combined with Quinine.Approved
RanitidineThe serum concentration of Venetoclax can be increased when it is combined with Ranitidine.Approved
RanolazineThe serum concentration of Venetoclax can be increased when it is combined with Ranolazine.Approved, Investigational
ReboxetineThe serum concentration of Venetoclax can be increased when it is combined with Reboxetine.Approved, Investigational
RegorafenibThe serum concentration of Venetoclax can be increased when it is combined with Regorafenib.Approved
ReserpineThe serum concentration of Venetoclax can be decreased when it is combined with Reserpine.Approved
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
RilpivirineThe serum concentration of Venetoclax can be increased when it is combined with Rilpivirine.Approved
RitonavirThe metabolism of Venetoclax can be decreased when combined with Ritonavir.Approved, Investigational
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
ScopolamineThe serum concentration of Venetoclax can be increased when it is combined with Scopolamine.Approved
SelegilineThe serum concentration of Venetoclax can be increased when it is combined with Selegiline.Approved, Investigational, Vet Approved
SertralineThe serum concentration of Venetoclax can be increased when it is combined with Sertraline.Approved
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
SimvastatinThe serum concentration of Venetoclax can be increased when it is combined with Simvastatin.Approved
SirolimusThe serum concentration of Venetoclax can be decreased when it is combined with Sirolimus.Approved, Investigational
SorafenibThe serum concentration of Venetoclax can be increased when it is combined with Sorafenib.Approved, Investigational
SpironolactoneThe serum concentration of Venetoclax can be increased when it is combined with Spironolactone.Approved
St. John's WortThe serum concentration of Venetoclax can be decreased when it is combined with St. John&#39;s Wort.Nutraceutical
StaurosporineThe serum concentration of Venetoclax can be increased when it is combined with Staurosporine.Experimental
StiripentolThe serum concentration of Venetoclax can be increased when it is combined with Stiripentol.Approved
StreptozocinThe serum concentration of Venetoclax can be decreased when it is combined with Streptozocin.Approved
SulfinpyrazoneThe serum concentration of Venetoclax can be increased when it is combined with Sulfinpyrazone.Approved
SulfisoxazoleThe metabolism of Venetoclax can be decreased when combined with Sulfisoxazole.Approved, Vet Approved
SumatriptanThe serum concentration of Venetoclax can be increased when it is combined with Sumatriptan.Approved, Investigational
SunitinibThe serum concentration of Venetoclax can be increased when it is combined with Sunitinib.Approved, Investigational
TacrineThe serum concentration of Venetoclax can be increased when it is combined with Tacrine.Withdrawn
TacrolimusThe serum concentration of Venetoclax can be decreased when it is combined with Tacrolimus.Approved, Investigational
TamoxifenThe serum concentration of Venetoclax can be decreased when it is combined with Tamoxifen.Approved
Taurocholic AcidThe serum concentration of Venetoclax can be increased when it is combined with Taurocholic Acid.Experimental
TelaprevirThe metabolism of Venetoclax can be decreased when combined with Telaprevir.Withdrawn
TelithromycinThe metabolism of Venetoclax can be decreased when combined with Telithromycin.Approved
TelmisartanThe serum concentration of Venetoclax can be increased when it is combined with Telmisartan.Approved, Investigational
TemsirolimusThe serum concentration of Venetoclax can be increased when it is combined with Temsirolimus.Approved
TerazosinThe serum concentration of Venetoclax can be increased when it is combined with Terazosin.Approved
TerfenadineThe serum concentration of Venetoclax can be increased when it is combined with Terfenadine.Withdrawn
TeriflunomideThe serum concentration of Venetoclax can be increased when it is combined with Teriflunomide.Approved
TesmilifeneThe serum concentration of Venetoclax can be decreased when it is combined with Tesmilifene.Investigational
TestosteroneThe serum concentration of Venetoclax can be increased when it is combined with Testosterone.Approved, Investigational
TicagrelorThe serum concentration of Venetoclax can be increased when it is combined with Ticagrelor.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
TolvaptanThe serum concentration of Venetoclax can be increased when it is combined with Tolvaptan.Approved
TrazodoneThe serum concentration of Venetoclax can be decreased when it is combined with Trazodone.Approved, Investigational
TrifluoperazineThe serum concentration of Venetoclax can be increased when it is combined with Trifluoperazine.Approved
TriflupromazineThe serum concentration of Venetoclax can be increased when it is combined with Triflupromazine.Approved, Vet Approved
TrimethoprimThe serum concentration of Venetoclax can be decreased when it is combined with Trimethoprim.Approved, Vet Approved
TrimipramineThe serum concentration of Venetoclax can be increased when it is combined with Trimipramine.Approved
VenlafaxineThe metabolism of Venetoclax can be decreased when combined with Venlafaxine.Approved
VerapamilThe metabolism of Venetoclax can be decreased when combined with Verapamil.Approved
VinblastineThe serum concentration of Venetoclax can be decreased when it is combined with Vinblastine.Approved
VincristineThe serum concentration of Venetoclax can be decreased when it is combined with Vincristine.Approved, Investigational
VinorelbineThe serum concentration of Venetoclax can be increased when it is combined with Vinorelbine.Approved, Investigational
VoriconazoleThe metabolism of Venetoclax can be decreased when combined with Voriconazole.Approved, Investigational
ZimelidineThe serum concentration of Venetoclax can be increased when it is combined with Zimelidine.Withdrawn
ZiprasidoneThe metabolism of Venetoclax can be decreased when combined with Ziprasidone.Approved
Food InteractionsNot Available
References
Synthesis ReferenceNot Available
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
ATC CodesNot Available
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelDownload (9.7 MB)
MSDSNot Available
Clinical Trials
Clinical Trials
PhaseStatusPurposeConditionsCount
1Active Not RecruitingTreatmentAcute Myelogenous Leukaemia (AML) / AML1
1Active Not RecruitingTreatmentAcute Myelogenous Leukaemia (AML) / Myelogenous Leukemia / Treatment Naive AML1
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 Myeloma2
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 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
1RecruitingTreatmentAcute Myeloid Leukaemias (AML)1
1RecruitingTreatmentAcute Myeloid Leukaemias (AML) / Cancer, Advanced / Cancer, Breast / Lung Cancer Small Cell Lung Cancer (SCLC) / Multiple Myeloma (MM) / Non-Hodgkin's Lymphoma (NHL) / Non-Small-Cell Lung Carcinoma (NSCLC) / Prostate Cancer1
1RecruitingTreatmentAcute Myeloid Leukaemias (AML) / Chronic Lymphocytic Leukaemia (CLL) / Chronic Lymphocytic Leumemia / Multiple Myeloma (MM) / Non-Hodgkin's Lymphoma (NHL) / Small Lymphocytic Lymphoma (SLL)1
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
1RecruitingTreatmentFollicular Lymphoma (FL)1
1RecruitingTreatmentHigh Grade B-cell Lymphoma / Lymphoma, Large B-Cell, Diffuse (DLBCL)1
1RecruitingTreatmentLymphoma, Large B-Cell, Diffuse (DLBCL)1
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
1SuspendedTreatmentLymphoma, Mantle-Cell / Recurrent Lymphoma, Mantle-Cell1
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, 2Not Yet RecruitingTreatmentAcute Myeloid Leukaemias (AML) / Other Diseases of Blood and Blood-Forming Organs1
1, 2Not Yet RecruitingTreatmentRecurrent Chronic Lymphocytic Leukemia / Recurrent Small Lymphocytic Lymphoma / Refractory Chronic Lymphocytic Leukemia / Refractory Small Lymphocytic Lymphoma1
1, 2RecruitingTreatmentFollicular Lymphoma (FL) / Lymphoma, Large B-Cell, Diffuse (DLBCL)1
1, 2RecruitingTreatmentLeukemia, Myeloid, Acute1
1, 2RecruitingTreatmentMantle Cell Lymphoma (MCL)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 RecruitingTreatmentFollicular Lymphoma (FL) / Relapsed or Refractory Follicular Lymphoma1
2CompletedTreatmentAcute Myelogenous Leukaemia (AML) / Acute Myeloid Leukaemias (AML) / AML1
2Not Yet RecruitingTreatmentChronic Lymphocytic Leukaemia (CLL)1
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) / Leukemia, Lymphocytic, Chronic, B-Cell / Small Lymphocytic Lymphoma (SLL)1
2RecruitingTreatmentChronic Lymphocytic Leukaemia (CLL) / Leukemias / Small Lymphocytic Lymphoma (SLL)1
2RecruitingTreatmentChronic Lymphocytic Leukaemia (CLL) / Small Lymphocytic Lymphoma (SLL)1
2RecruitingTreatmentLeukemia, Lymphocytic, Chronic1
2RecruitingTreatmentLymphoma, Large B-Cell, Diffuse (DLBCL)1
2RecruitingTreatmentMantle Cell Lymphoma (MCL)1
2RecruitingTreatmentRelapsed Or Refractory Multiple Myeloma1
2RecruitingTreatmentRichter's Syndrome1
2RecruitingTreatmentWaldenstrom's Macroglobulinemia (WM)1
2SuspendedTreatmentTreatment-Naïve Higher-Risk Myelodysplastic Syndromes (MDS)1
3Active Not RecruitingTreatmentChronic Lymphocytic Leukaemia (CLL)1
3Active Not RecruitingTreatmentLymphocytic Leukemia, Chronic1
3RecruitingTreatmentAcute Myeloid Leukaemias (AML)2
3RecruitingTreatmentChronic Lymphocytic Leukaemia (CLL)3
3RecruitingTreatmentRelapsed/Refractory Multiple Myeloma1
Not AvailableAvailableNot AvailableAcute Myeloid Leukaemias (AML) / Chronic Lymphocytic Leukaemia (CLL) / Multiple Myeloma (MM) / Non-Hodgkin's Lymphoma (NHL)1
Pharmacoeconomics
ManufacturersNot Available
PackagersNot 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
PricesNot Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US9174982 No2010-05-262030-05-26Us
US8546399 No2011-06-272031-06-27Us
Properties
StateSolid
Experimental PropertiesNot 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 featuresNot Available
Spectra
Mass Spec (NIST)Not Available
Spectra
Spectrum TypeDescriptionSplash Key
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, NegativeNot Available
Taxonomy
DescriptionThis 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.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassDiazinanes
Sub ClassPiperazines
Direct ParentPhenylpiperazines
Alternative ParentsN-arylpiperazines / Aminobenzenesulfonamides / Diarylethers / Aminobenzoic acids and derivatives / Pyrrolopyridines / Benzenesulfonyl compounds / Nitrobenzenes / Aniline and substituted anilines / Benzoyl derivatives / Dialkylarylamines
SubstituentsN-arylpiperazine / Phenylpiperazine / Diaryl ether / Aminobenzenesulfonamide / Benzenesulfonamide / Aminobenzoic acid or derivatives / Nitrobenzene / Benzoic acid or derivatives / Pyrrolopyridine / Benzenesulfonyl group
Molecular FrameworkAromatic heteropolycyclic compounds
External DescriptorsNot 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. Appears to function in a feedback loop system with caspases. Inhibits caspase activity either by preventing the release of cytochrome c from the mitochondria and/or by binding to the apoptosis-activating f...
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 reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4-hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiot...
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 from mitochondria to cytosol and from cytosol to extracellular space, and cellular export of hemin, and heme. Xenobiotic transporter that may play an important role in the exclusion of xenobiotics from t...
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 September 01, 2017 12:10