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Venetoclax (ABT-199) Bcl-2 inhibitor

Name: Venetoclax (ABT-199)
Brand: Selleck Chemicals
SKU: S8048
Availability: InStock
Rating: 5 (625 reviews)

Cat.No.S8048

Venetoclax (ABT-199, GDC-0199) is a Bcl-2-selective inhibitor with K_i of <0.01 nM in cell-free assays, >4800-fold more selective versus Bcl-xL and Bcl-w, and no activity to Mcl-1. This compound is reported to induce cell growth suppression, apoptosis, cell cycle arrest, and autophagy in triple negative breast cancer MDA-MB-231 cells. Phase 3.

Chemical Structure

Molecular Weight: 868.44

Jump to Mechanism of Action Cell Culture & Working Concentration Solubility Chemical Information, Storage & Stability Specificity

Quality Control

Batch: Purity: 99.97%

99.97

Products Often Used Together with Venetoclax (ABT-199)

A-1210477

This compound and A-1210477 increase MCL1 expression and synergistically induce apoptosis in acute myeloid leukemia (AML) cells, MOLM13/MV4-11/SKM1/OCI-AML5.

Navitoclax (ABT-263)

It, Navitoclax and chemotherapy show promising efficacy and tolerability in patients with relapsed/refractory acute lymphoblastic leukemia.

S63845

It and S63845 significantly delay the time to viral rebound by 4-fold after antiretroviral therapy (ART) cessation in a humanized mouse model of HIV-1 infection.

Related Targets	Apoptosis related Ras STAT TNF-alpha Caspase PD-1/PD-L1 Ferroptosis p53 RIP kinase c-RET MDM2/MDMX Myc Antifolate MRP IAP OXPHOS PERK FKBP Thymidylate Synthase ABC Transporter Heme Oxygenase PFKFB Pyroptosis Photosensitizer PKD Survivin Annexin A ASK Bcl-6 Nur77
Related Products	ABT-737 Navitoclax (ABT-263) Obatoclax Mesylate (GX15-070) S63845 A-1210477 TW-37 A-1331852 A-1155463 Dihydrochloride UMI-77 AZD5991 (R)-(-)-Gossypol (AT-101) acetic acid Sabutoclax WEHI-539 HA14-1 MIK665 (S64315) Obatoclax (GX15-070) Gambogic Acid Marinopyrrole A (Maritoclax) BAI1 A-1155463 BTSA1 S55746 Ruxotemitide (LTX 315) BAM7 BDA-366 Solanum lyratum Extract Bcl-2 Antibody [H20N17] Bcl-w Antibody [G2B1] BNIP3L/Nix Antibody [K19B13] APG-2575 (lisaftoclax)

Cell Culture, Treatment & Working Concentration

Cell Lines	Assay Type	Concentration	Incubation Time	Formulation	Activity Description	PMID
CS-THL1	Growth Inhibition Assay	20 nM	72 h	DMSO	Inhibits cell growth assessed by cell viability	25916698
CS-THL1	Apoptotic Assay	25 nM		DMSO	Induces apoptosis	25916698
DoGKiT	Apoptotic Assay	50 nM		DMSO	Induces apoptosis	25916698
RS4-11	Growth Inhibition Assay		72 h		IC50=0.0402 μM	25649768
NALM-6	Growth Inhibition Assay		72 h		IC50>3 μM	25649768
SU-DHL-6	Growth Inhibition Assay	0.8 μM			Inhibits cell growth assessed by cell viability	25590803
OCI-Ly19	Growth Inhibition Assay	1 μM			Inhibits cell growth assessed by cell viability	25590803
SU-DHL-6	Function Assay	0.75 μM	18 h		Increases pro-survival protein MCL-1 expression	25590803
KCL22	Function Assay	2 μM	48 h	DMSO	Increases DNA fragamentation	25333252
LOUCY	Growth Inhibition Assay	10 μM	48 h	DMSO	IC50=0.0139 μM	25301704
ALL-SIL	Growth Inhibition Assay	10 μM	48 h	DMSO	IC50=0.1803 μM	25301704
CUTLL1	Growth Inhibition Assay	10 μM	48 h	DMSO	IC50=0.3823 μM	25301704
KOPTK1	Growth Inhibition Assay	10 μM	48 h	DMSO	IC50=0.6432 μM	25301704
DND-41	Growth Inhibition Assay	10 μM	48 h	DMSO	IC50=1.9695 μM	25301704
PF-382	Growth Inhibition Assay	10 μM	48 h	DMSO	IC50=2.1824 μM	25301704
KARPAS-45	Growth Inhibition Assay	10 μM	48 h	DMSO	IC50=3.2225 μM	25301704
PEER	Growth Inhibition Assay	10 μM	48 h	DMSO	IC50=4.6403 μM	25301704
CX-1	Growth Inhibition Assay	100 μM	72 h		IC50=6.7 μM	25208882
LS147T	Growth Inhibition Assay	100 μM	72 h		IC50=29.5 μM	25208882
HL-60	Growth Inhibition Assay		48 h		IC50<1 μM	24346116
MOLM-13	Growth Inhibition Assay		48 h		IC50<1 μM	24346116
OCI-AML2	Growth Inhibition Assay		48 h		IC50<1 μM	24346116
Kasumi-1	Growth Inhibition Assay		48 h		IC50<1 μM	24346116
KG-1	Growth Inhibition Assay		48 h		IC50<1 μM	24346116
THP-1	Growth Inhibition Assay		48 h		IC50<1 μM	24346116
MOLM-14	Growth Inhibition Assay		48 h		IC50<1 μM	24346116
MOLM-13	Apoptotic Assay	50 nM	24 h		Apoptosis induction	24346116
HSB	Growth Inhibition Assay	10 μM	48 h	DMSO	IC50=4.448 μM	24342948
MOLT4	Growth Inhibition Assay	10 μM	48 h	DMSO	IC50=4.154 μM	24342948
SKW-3/KE-37	Growth Inhibition Assay	10 μM	48 h	DMSO	IC50=0.712 μM	24342948
SUPT-11	Growth Inhibition Assay	10 μM	48 h	DMSO	IC50=4.473 μM	24342948
JURKAT	Growth Inhibition Assay	10 μM	48 h	DMSO	IC50=4.893 μM	24342948
CCRF-CEM	Growth Inhibition Assay	10 μM	48 h	DMSO	IC50=1.360 μM	24342948
LOUCY	Apoptotic Assay	2 μM	48 h	DMSO	Apoptosis induction	24342948
RS4:11	Cytotoxicity assay					29407973
RS4:11	MTS assay		72 h			30278333
RS4:11	MTS assay					28926247
Toledo	MTS assay		72 h			30278333
NCI60	SRB assay		48 h			27994761
RS4:11	MTT assay		24 h			29453135
melanoma	SRB assay		48 h			27994761
leukemia	SRB assay		48 h			27994761
renal cancer	SRB assay		48 h			27994761
non-small cell lung cancer	SRB assay		48 h			27994761
breast cancer	SRB assay		48 h			27994761
colon cancer	SRB assay		48 h			27994761
ovarian cancer	SRB assay		48 h			27994761
CNS cancer	SRB assay		48 h			27994761
prostate cancer	SRB assay		48 h			27994761
Remb1	MTT assay		24 h			29453135
Click to View More Cell Line Experimental Data

Chemical Information, Storage & Stability

Molecular Weight	868.44	Formula	C₄₅H₅₀ClN₇O₇S	Storage (From the date of receipt)	3 years-20°Cpowder
CAS No.	1257044-40-8	Download SDF		Storage of Stock Solutions	1 year-80°Cin solvent 1 month-20°Cin solvent
Synonyms	GDC-0199			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

Solubility

In vitro
Batch:

DMSO : 100 mg/mL (115.14 mM)
(Moisture-contaminated DMSO may reduce solubility. Use fresh, anhydrous DMSO.)

Water : Insoluble

Ethanol : Insoluble

DMSO : 250 mg/mL (287.87 mM) Warmed with 50°C water bath; Ultrasonicated;
(Moisture-contaminated DMSO may reduce solubility. Use fresh, anhydrous DMSO.)

Water : Insoluble

Ethanol : Insoluble

Molarity Calculator

Mass	Concentration	Volume	Molecular Weight
Mass value Mass unit	Concentration value Concentration unit	Volume value Volume unit	Molecular weight (g/mol)

Dilution Calculator Molecular Weight Calculator

In vivo batch selection In vivo Batch:
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Clear solution	5%DMSO 1 Corn oil Validated by Selleck labs. Should you need adjustments to this formulation, contact our sales team for custom testing.	2.500mg/ml (2.88mM)	Taking the 1 mL working solution as an example, add 50 μL of 50 mg/ml clear DMSO stock solution to 950 μL of corn oil and mix evenly. The mixed solution should be used immediately for optimal results.
Clear solution	10% DMSO 1 40% PEG 300 2 5%Tween80 3 45%ddH2O Validated by Selleck labs. Should you need adjustments to this formulation, contact our sales team for custom testing.	1.800mg/ml (2.07mM)	Taking the 1 mL working solution as an example, add 100 μL of 18 mg/ml clarified DMSO stock solution to 400 μL of PEG300, mix evenly to clarify it; add 50 μL of Tween80 to the above system, mix evenly to clarify; then continue to add 450 μL of ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Clear solution	5%DMSO 1 50%PEG300 2 5%Tween80 3 40%ddH2O Validated by Selleck labs. Should you need adjustments to this formulation, contact our sales team for custom testing.	2.500mg/ml (2.88mM)	Taking the 1 mL working solution as an example, add 50 μL of 50 mg/ml clarified DMSO stock solution to 500 μL of PEG300, mix evenly to clarify it; add 50 μL of Tween80 to the above system, mix evenly to clarify; then continue to add 400 μL of ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)

Dosage: mg/kg

Average weight of animals: g

Dosing volume per animal: μL

Number of animals:

Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)

% DMSO

% Tween 80

% ddH₂O

% DMSO

Calculation results:

Working concentration: mg/ml;

Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )

Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH₂O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such
as vortex, ultrasound or hot water bath can be used to aid dissolving.

Mechanism of Action

Features	Re-engineered version of ABT-263 (Navitoclax).
Targets/IC₅₀/Ki	Bcl-2 ^[1] (Cell-free assay) <0.01 nM(Ki)
In vitro	Venetoclax (ABT-199) shows less sensitivity to Bcl-xL, Mcl-1 and Bcl-w with K_i of 48 nM, > 444 nM and 245 nM, respectively. It potently inhibits FL5.12-Bcl-2 cells, RS4;11 cells with EC50 of 4 nM and 8 nM, while shows low activity against FL5.12-Bcl-xL cells with EC50 of 261 nM. This compound induces a rapid apoptosis in RS4;11 cells with cytochrome c release, caspase activation, the externalization of phosphatidylserine and the accumulation of sub-G0/G1 DNA. Quantitative immunoblotting reveals that sensitivity to it correlated strongly with the expression of Bcl-2, including NHL, DLBCL, MCL, AML and ALL cell lines. It also induces apoptosis in CLL with an average EC50 of 3.0 nM. ^[1]
Kinase Assay	Binding affinity assays
Kinase Assay	Binding affinities (K_i or IC50) of Venetoclax (ABT-199) against different isoforms of Bcl-2 family are determined with competitive fluorescence polarization assays. The following peptide probe/protein pairs are used: f-bad (1 nM) and Bcl-xL (6 nM), f-Bax (1 nM) and Bcl-2 (10 nM), f-Bax (1 nM) and Bcl-w (40 nM), f-Noxa (2 nM) and Mcl-1 (40 nM), and f-Bax (1 nM) and Bcl-2-A1 (15 nM). Its binding affinities for Bcl-xL are also determined using a time-resolved fluorescence resonance energy transfer assay. In this assay, Bcl-xL (1 nM, His tagged) is mixed with 200 nM f-Bak, 1 nM Tb-labeled anti-His antibody, and the compound at room temperature for 30 min. Fluorescence is measured on an Envision plate reader using a 340/35 nm excitation filter and 520/525 (f-Bak) and 495/510 nm (Tb-labeled anti-His antibody) emission filters.
In vivo	Venetoclax (ABT-199) causes a maximal tumor growth inhibition of 95% and tumor growth delay of 152% in RS4;11 xenografts. It also inhibits xenograft growth (DoHH2, Granta-519) as a single agent or in combination with SDX-105 and other agents. ^[1]
References	[1] https://pubmed.ncbi.nlm.nih.gov/23291630/

Applications

Methods	Biomarkers	PMID
Western blot	Mcl-1 / Bcl-xl / Bcl-2 / Bak / NOXA / Bim PARP / Cleaved PARP / Caspase 3 / Cleaved caspase3 / p-S6(Ser236/236)	30663221
Growth inhibition assay	Cell death Cell viability	28714472
Immunofluorescence	Bcl-2 / Mcl-1	28767232

Clinical Trial Information

(data from https://clinicaltrials.gov, updated on 2024-05-22)

NCT Number	Recruitment	Conditions	Sponsor/Collaborators	Start Date	Phases
NCT06382168	Not yet recruiting	Leukemia Myeloid Acute	Delta-Fly Pharma Inc.	May 31 2024	Phase 1\|Phase 2
NCT06263387	Not yet recruiting	AML Adult	French Innovative Leukemia Organisation\|Acute Leukemia French Association	April 29 2024	--

Tech Support

Handling Instructions

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Frequently Asked Questions

Question 1:
Could you please offer some advice on the half-life of it ?

Answer:
According to the reference (https://www.ncbi.nlm.nih.gov/pubmed/24212376), its half-life in dogs is 12.9 hr.

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