General
Preferred name
VENETOCLAX
Synonyms
ABT-199 ()
ABT 199 ()
GDC-0199 ()
ABT199 ()
UNII-N54AIC43PW ()
C45H50ClN7O7S ()
VENCLEXTA ()
A-1231 ()
4-[4-[[2-(4-Chlorophenyl)-4,4-dimethylcyclohex-1-en-1-yl]methyl]piperazin-1-yl]-N-[[3-nitro-4-[[(tetrahydro-2H-pyran-4-yl)methyl]amino]phenyl]sulfonyl]-2-[(1H-pyrrolo[2,3-b]pyridin-5-yl)oxy]benzamide ()
RG7601 ()
chronic lymphocytic leukaemia therapy, AbbVie ()
Venetoclax (ABT-199) ()
Venclyxto ()
RG-7601 ()
P&D ID
PD003393
CAS
1257044-40-8
Tags
available
probe
drug
Approved by
FDA
EMA
PMDA
First approval
2016
Drug indication
Chronic lymphocytic leukemia
Solid tumour/cancer
Chronic lymphocytic leukaemia
Drug Status
approved
investigational
Max Phase
4.0
Probe info
Probe selectivity
protein-selective
Probe type
experimental probe
P&D approved
Probe sources
Probe targets
[[ compound.targets[t].gene_name ]]
Probe control
Probe control not defined
Orthogonal probes
1
No orthogonal probes found
Similar probes
6
No structurally similar probes found
Structure
P&D probe-likeness score
Structure formats
[[ format ]]
[[ compound[format === 'MOL' ? 'molblock' : format.toLowerCase()] ]]
Description
(extracted from source data)
TOXICITY
**Acute toxicity**: oral toxicity (LD50) >2001 mg/kg (mouse) [L4816].; ; Venetoclax may cause embryo-fetal harm when administered to a pregnant woman. Patients should avoid pregnancy during treatment. A risk to human male fertility exists based on the results of testicular toxicity (germ cell loss) seen in dogs at exposures as low as 0.5 times the human AUC exposure at the recommended dose [FDA label].; ; Carcinogenicity studies have not yet been performed with venetoclax [FDA label].; ; Venetoclax was not shown to be mutagenic in an in vitro bacterial mutagenicity (Ames) assay, did not induce aberrations in an in vitro chromosome aberration assay with human peripheral blood lymphocytes. It was not clastogenic in an in vivo mouse bone marrow micronucleus assay at doses up to 835 mg/kg. The M27 metabolite was negative for genotoxic activity during both in vitro Ames and chromosome aberration assays [FDA label].
ABSORPTION
Following several oral administrations after a meal, the maximum plasma concentration of venetoclax was reached 5-8 hours after the dose [A18567]. Venetoclax steady state AUC (area under the curve) increased proportionally over the dose range of 150-800 mg. After a low-fat meal, venetoclax mean (± standard deviation) steady-state Cmax was 2.1 ± 1.1 μg/mL and AUC0-24 was 32.8 ± 16.9 μgâ¢h/mL at the 400 mg once daily dose [FDA label]. ; ; When compared with the fasted state, venetoclax exposure increased by 3.4 times when ingested with a low-fat meal and 5.2 times with a high-fat meal. When comparing low versus high fat, the Cmax and AUC were both increased by 50% when ingested with a high-fat meal. The FDA label indicataes that venetoclax should be taken with food [A40022], [FDA label].
COMMENT
Early studies with Venetoclax (ABT-199), a potent and selective orally-bioavailable B-cell lymphoma 2 small-molecule inhibitor, which has shown an remarkable response across a number of hematologic malignancies, with an acceptable safety profile. This drug has been approved by the US Food and Drug Administration and the European Medicines Agency for treatment of adult patients with 17p deleted relapsed/refractory chronic lymphocytic leukemia (del(17p) CLL) Venetoclax is sold under the brand names Venclexta and Venclyxto. Nov 11 2020 - 10:57am
DESCRIPTION
Venetoclax is a BH3 mimetic that selectively targets Bcl-2 , utilised for its pro-apoptotic activity. It is noteworthy that venetoclax is the first approved medicine designed to induce a natural process that helps cells self-destruct.
The IUPAC name provided by PubChem matches 'Example 5' claimed in patent US8580794 . (GtoPdb)
The IUPAC name provided by PubChem matches 'Example 5' claimed in patent US8580794 . (GtoPdb)
MOA
BH3 mimetic
(Chemical Probes.org)
DESCRIPTION
inhibitor of BCL2
(Informer Set)
DESCRIPTION
Frizzled 4 allosteric agonist; exhibits biased siginaling; preserves stemness
(Tocris Bioactive Compound Library)
[[ p.pathway_name ]]
[[ compound.targets[tid].gene_name ]]
Cell lines
9
Organisms
0
Compound Sets
28
AdooQ Bioactive Compound Library
Axon Medchem Screening Library
Cayman Chemical Bioactives
ChEMBL Approved Drugs
ChEMBL Drugs
Chemical Probes.org
CZ-OPENSCREEN Bioactive Library
Drug Repurposing Hub
DrugBank
DrugBank Approved Drugs
DrugCentral
DrugCentral Approved Drugs
EU-OPENSCREEN Bioactive Compound Library
EUbOPEN Chemogenomics Library
Guide to Pharmacology
High-quality chemical probes
Informer Set
IPPI - DB
MedChem Express Bioactive Compound Library
NCATS Inxight Approved Drugs
NIH Approved Oncology Drugs
Novartis Chemogenetic Library (NIBR MoA Box)
ReFrame library
Selleckchem Bioactive Compound Library
TargetMol Bioactive Compound Library
Tocris Bioactive Compound Library
[[ a.name ]]
[[ ligand_id ]]
free of charge
External IDs
38
Molecular Weight
867.32
Hydrogen Bond Acceptors
11
Hydrogen Bond Donors
3
Rotatable Bonds
13
Ring Count
8
Aromatic Ring Count
5
cLogP
8.66
TPSA
172.03
Fraction CSP3
0.38
Chiral centers
0.0
Largest ring
6.0
QED
0.08
Structural alerts
0
No structural alerts detected
Related compounds
Custom attributes
(extracted from source data)
Target
BCL2
Bcl-2
Bcl-2 inhibitor
Autophagy,Bcl-2
Compound status
clinical
Pathway
Apoptosis
Autophagy
Primary Target
Bcl-2 Family
MOA
BCL
Inhibitor
Bcl-2 inhibtion, apoptosis inducer
BCL2 inhibitor
BCL inhibitor
Member status
member
Indication
chronic lymphocytic leukemia (CLL)
Target subclass
Protein Phosphatase
Recommended Cell Concentration
None
Source data
