Details of the Drug

General Information of Drug (ID: DM8I94Y)

Drug Name

Venetoclax

Synonyms

Venclexta

Indication

Disease Entry	ICD 11	Status	REF
Chronic lymphocytic leukaemia	2A82.0	Approved	[1]

Affected Organisms

Humans and other mammals

ATC Code

L01XX52: Venetoclax

L01XX: Other antineoplastic agents

L01X: OTHER ANTINEOPLASTIC AGENTS

L01: ANTINEOPLASTIC AGENTS

L: ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS

Drug Type

Small molecular drug

Structure

3D MOL

2D MOL

#Ro5 Violations (Lipinski):
3

Molecular Weight

868.447

Logarithm of the Partition Coefficient

Not Available

Rotatable Bond Count

Hydrogen Bond Donor Count

Hydrogen Bond Acceptor Count

ADMET Property

Absorption AUC: The area under the plot of plasma concentration (AUC) of drug is 32.8 +/- 16.9 mgh/L [2]
Absorption Cmax: The maximum plasma concentration (Cmax) of drug is 2.1 +/- 1.1 mg/L [2]
Absorption Tmax: The time to maximum plasma concentration (Tmax) is 5-8 h [2]
Clearance: The drug is mainly cleared by the liver []
Elimination: After single oral administration of 200 mg radiolabeled [14C]-venetoclax dose to healthy subjects, >99.9% of the dose was found in feces and <0.1% of the dose was excreted in urine within 9 days, suggesting that hepatic elimination is responsible for the clearance of venetoclax from systemic circulation []
Half-life: The concentration or amount of drug in body reduced by one-half in 19 - 26 hours [3]
Metabolism: The drug is metabolized via the CYP3A4/5 [4]
Vd: The volume of distribution (Vd) of drug is 256-321 L []

Chemical Identifiers

Formula: C45H50ClN7O7S
IUPAC Name: 4-[4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohexen-1-yl]methyl]piperazin-1-yl]-N-[3-nitro-4-(oxan-4-ylmethylamino)phenyl]sulfonyl-2-(1H-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide
Canonical SMILES: CC1(CCC(=C(C1)C2=CC=C(C=C2)Cl)CN3CCN(CC3)C4=CC(=C(C=C4)C(=O)NS(=O)(=O)C5=CC(=C(C=C5)NCC6CCOCC6)[N+](=O)[O-])OC7=CN=C8C(=C7)C=CN8)C
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)
InChIKey: LQBVNQSMGBZMKD-UHFFFAOYSA-N

Cross-matching ID

PubChem CID: 49846579
ChEBI ID: CHEMBL3137309
CAS Number: 1257044-40-8
UNII: N54AIC43PW
DrugBank ID: DB11581
VARIDT ID: DR00008

Drug-Molecule Activity Atlas (DMA)^NEW

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Drug ADMET Endpoint Profile (DAE)^NEW

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Combinatorial Drugs (CBD)

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Molecular Interaction Atlas of This Drug

Drug Transporter (DTP)

DTP Name	DTP ID	UniProt ID	MOA	REF
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[5]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Bcl-2 homologous antagonist/killer (BAK1)	OTDP6ILW	BAK_HUMAN	Protein Interaction/Cellular Processes	[6]
Bcl-2-binding component 3, isoforms 3/4 (BBC3)	OTUAXDAY	BBC3B_HUMAN	Drug Response	[7]
Bcl-2-like protein 1 (BCL2L1)	OTRC5K9O	B2CL1_HUMAN	Gene/Protein Processing	[6]
Broad substrate specificity ATP-binding cassette transporter ABCG2 (ABCG2)	OTW8V2V1	ABCG2_HUMAN	Protein Interaction/Cellular Processes	[8]
Phorbol-12-myristate-13-acetate-induced protein 1 (PMAIP1)	OTXEE550	APR_HUMAN	Gene/Protein Processing	[6]
Poly polymerase 1 (PARP1)	OT310QSG	PARP1_HUMAN	Protein Interaction/Cellular Processes	[9]
Receptor-type tyrosine-protein kinase FLT3 (FLT3)	OTMSRYMK	FLT3_HUMAN	Gene/Protein Processing	[10]

Molecular Interaction Atlas (MIA)

MIA Detail

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References

1	Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
2	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.
3	Venetoclax: A First-in-Class Oral BCL-2 Inhibitor for the Management of Lymphoid Malignancies. Ann Pharmacother. 2017 May;51(5):410-416. doi: 10.1177/1060028016685803. Epub 2017 Jan 6.
4	PEETS EA, SWEENEY WM, PLACE VA, BUYSKE DA: THE ABSORPTION, EXCRETION, AND METABOLIC FATE OF ETHAMBUTOL IN MAN. Am Rev Respir Dis. 1965 Jan;91:51-8. doi: 10.1164/arrd.1965.91.1.51.
5	Venclexta FDA label
6	Superior efficacy of cotreatment with BET protein inhibitor and BCL2 or MCL1 inhibitor against AML blast progenitor cells. Blood Cancer J. 2019 Jan 15;9(2):4. doi: 10.1038/s41408-018-0165-5.
7	Statin-induced Mitochondrial Priming Sensitizes Multiple Myeloma Cells to BCL2 and MCL-1 Inhibitors. Cancer Res Commun. 2023 Dec 8;3(12):2497-2509. doi: 10.1158/2767-9764.CRC-23-0350.
8	Prospective Drug Candidates as Human Multidrug Transporter ABCG2 Inhibitors: an In Silico Drug Discovery Study. Cell Biochem Biophys. 2021 Jun;79(2):189-200. doi: 10.1007/s12013-021-00985-y. Epub 2021 May 5.
9	ZCL-082, a boron-containing compound, induces apoptosis of non-Hodgkin's lymphoma via targeting p90 ribosomal S6 kinase 1/NF-B signaling pathway. Chem Biol Interact. 2022 Jan 5;351:109770. doi: 10.1016/j.cbi.2021.109770. Epub 2021 Nov 30.
10	HSP90 Inhibitor PU-H71 in Combination with BH3-Mimetics in the Treatment of Acute Myeloid Leukemia. Curr Issues Mol Biol. 2023 Aug 23;45(9):7011-7026. doi: 10.3390/cimb45090443.