HY-15531-10mg | Venetoclax [1257044-40-8] Clinisciences

Description

Venetoclax (ABT-199; GDC-0199) is a highly potent, selective and orally bioavailable Bcl-2 inhibitor with a K_i of less than 0.01 nM. Venetoclax induces autophagy^[1]^[2]^[3].

IC₅₀ & Target^[1]

Bcl-2

0.01 nM (Ki)

Bcl-xL

48 nM (Ki)

Bcl-W

245 nM (Ki)

Cellular Effect

Cell Line	Type	Value	Description	References
Cancer cell lines	GI₅₀	2.6 μM Compound: ABT-199	Cytotoxicity against human renal cancer cells assessed as cell growth inhibition after 48 hrs by SRB assay Cytotoxicity against human renal cancer cells assessed as cell growth inhibition after 48 hrs by SRB assay	[PMID: 27994761]
Cancer cell lines	GI₅₀	2.7 μM Compound: ABT-199	Cytotoxicity against human non-small cell lung cancer cells assessed as cell growth inhibition after 48 hrs by SRB assay Cytotoxicity against human non-small cell lung cancer cells assessed as cell growth inhibition after 48 hrs by SRB assay	[PMID: 27994761]
Cancer cell lines	GI₅₀	2.77 μM Compound: ABT-199	Cytotoxicity against human breast cancer cells assessed as cell growth inhibition after 48 hrs by SRB assay Cytotoxicity against human breast cancer cells assessed as cell growth inhibition after 48 hrs by SRB assay	[PMID: 27994761]
Cancer cell lines	GI₅₀	2.85 μM Compound: ABT-199	Cytotoxicity against human colon cancer cells assessed as cell growth inhibition after 48 hrs by SRB assay Cytotoxicity against human colon cancer cells assessed as cell growth inhibition after 48 hrs by SRB assay	[PMID: 27994761]
Cancer cell lines	GI₅₀	3.33 μM Compound: ABT-199	Cytotoxicity against human ovarian cancer cells assessed as cell growth inhibition after 48 hrs by SRB assay Cytotoxicity against human ovarian cancer cells assessed as cell growth inhibition after 48 hrs by SRB assay	[PMID: 27994761]
Cancer cell lines	GI₅₀	3.35 μM Compound: ABT-199	Cytotoxicity against human CNS cancer cells assessed as cell growth inhibition after 48 hrs by SRB assay Cytotoxicity against human CNS cancer cells assessed as cell growth inhibition after 48 hrs by SRB assay	[PMID: 27994761]
Cancer cell lines	GI₅₀	3.51 μM Compound: ABT-199	Cytotoxicity against human prostate cancer cells assessed as cell growth inhibition after 48 hrs by SRB assay Cytotoxicity against human prostate cancer cells assessed as cell growth inhibition after 48 hrs by SRB assay	[PMID: 27994761]
HEK-293T	IC₅₀	> 20 μM Compound: ABT-199	Cytotoxicity against HEK293T cells assessed as reduction in cell viability incubated for 48 hrs by CCK8 assay Cytotoxicity against HEK293T cells assessed as reduction in cell viability incubated for 48 hrs by CCK8 assay	[PMID: 34228434]
HeLa	IC₅₀	> 20 μM Compound: ABT-199	Cytotoxicity against human HeLa cells assessed as inhibition of cell growth incubated for 48 hrs by CCK8 assay Cytotoxicity against human HeLa cells assessed as inhibition of cell growth incubated for 48 hrs by CCK8 assay	[PMID: 34228434]
HL-60	IC₅₀	0.077 μM Compound: ABT-199	Cytotoxicity against human HL-60 cells assessed as inhibition of cell growth incubated for 48 hrs by CCK8 assay Cytotoxicity against human HL-60 cells assessed as inhibition of cell growth incubated for 48 hrs by CCK8 assay	[PMID: 34228434]
HL-60	EC₅₀	8.1 μM Compound: ABT-199	Induction of apoptosis in human HL-60 cells measured after 48 hrs by FITC-Annexin V/PS staining based Induction of apoptosis in human HL-60 cells measured after 48 hrs by FITC-Annexin V/PS staining based	[PMID: 33197310]
K562	EC₅₀	2.1 μM Compound: ABT199	Cytotoxicity against human K562 cells assessed as cell survival measured after 72 hrs by MTT assay Cytotoxicity against human K562 cells assessed as cell survival measured after 72 hrs by MTT assay	[PMID: 34216984]
KG-1	EC₅₀	0.85 μM Compound: ABT-199	Induction of apoptosis in human KG-1 cells measured after 48 hrs by FITC-Annexin V/PS staining based Induction of apoptosis in human KG-1 cells measured after 48 hrs by FITC-Annexin V/PS staining based	[PMID: 33197310]
Leukemia cell	GI₅₀	2.11 μM Compound: ABT-199	Cytotoxicity against human leukemia cells assessed as cell growth inhibition after 48 hrs by SRB assay Cytotoxicity against human leukemia cells assessed as cell growth inhibition after 48 hrs by SRB assay	[PMID: 27994761]
MCF7	EC₅₀	1.35 μM Compound: ABT-199	Induction of apoptosis in human MCF7 cells measured after 48 hrs by FITC-Annexin V/PS staining based Induction of apoptosis in human MCF7 cells measured after 48 hrs by FITC-Annexin V/PS staining based	[PMID: 33197310]
Melanoma cell	GI₅₀	1.75 μM Compound: ABT-199	Cytotoxicity against human melanoma cells assessed as cell growth inhibition after 48 hrs by SRB assay Cytotoxicity against human melanoma cells assessed as cell growth inhibition after 48 hrs by SRB assay	[PMID: 27994761]
OCI-AML-3	EC₅₀	6.8 μM Compound: ABT-199	Induction of apoptosis in human OCI-AML-3 cells measured after 48 hrs by FITC-Annexin V/PS staining based Induction of apoptosis in human OCI-AML-3 cells measured after 48 hrs by FITC-Annexin V/PS staining based	[PMID: 33197310]
RPMI-8226	IC₅₀	2.7 μM Compound: ABT-199	Growth inhibition of human RPMI8226 cells after 72 hrs by MTT assay Growth inhibition of human RPMI8226 cells after 72 hrs by MTT assay	[PMID: 30594434]
RS4-11	IC₅₀	0.0043 μM Compound: ABT-199	Cytotoxicity against human RS4-11 cells assessed as inhibition of cell growth incubated for 48 hrs by CCK8 assay Cytotoxicity against human RS4-11 cells assessed as inhibition of cell growth incubated for 48 hrs by CCK8 assay	[PMID: 34228434]
RS4-11	IC₅₀	0.006 μM Compound: ABT-199; 1	Antiproliferative activity against human RS4:11 cells after 72 hrs by MTS assay Antiproliferative activity against human RS4:11 cells after 72 hrs by MTS assay	[PMID: 30278333]
RS4-11	IC₅₀	0.33 μM Compound: ABT-199	Cytotoxicity against human RS4:11 cells assessed as reduction in cell viability after 24 hrs by MTT assay Cytotoxicity against human RS4:11 cells assessed as reduction in cell viability after 24 hrs by MTT assay	[PMID: 29453135]
RS4-11	IC₅₀	1.8 nM Compound: 6; ABT-199	Antiproliferative activity against human RS4-11 cells assessed as inhibition of cell proliferation measured after 72 hrs by CCK8 assay Antiproliferative activity against human RS4-11 cells assessed as inhibition of cell proliferation measured after 72 hrs by CCK8 assay	[PMID: 34536651]
Toledo	IC₅₀	0.011 μM Compound: ABT-199; 1	Antiproliferative activity against human Toledo cells after 72 hrs by MTS assay Antiproliferative activity against human Toledo cells after 72 hrs by MTS assay	[PMID: 30278333]
U-266	IC₅₀	94 μM Compound: ABT-199	Growth inhibition of human U266 cells after 72 hrs by MTT assay Growth inhibition of human U266 cells after 72 hrs by MTT assay	[PMID: 30594434]

In Vitro

Venetoclax (ABT-199) potently kills FL5.12-BCL-2 cells (EC₅₀=4 nM), Venetoclax (ABT-199) shows much weaker activity against FL5.12-BCL-XL cells (EC₅₀=261 nM). ABT-199 also shows selectivity in cellular mammalian two-hybrid assays, where it disrupts BCL-2-BIM complexes (EC₅₀=3 nM) but is much less effective against BCL-XL-BCL-XS (EC₅₀=2.2 μM) or MCL-1-NOXA complexes^[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

In Vivo

After a single oral dose of 12.5 mg per kg body weight in xenografts derived from RS4;11 cells (ALL), Venetoclax (ABT-199) causes a maximal tumor growth inhibition (TGI_max) of 47% (P<0.001) and tumor growth delay (TGD) of 26% (P<0.05)^[1].
Treatment of established xenografted (a mouse xenograft model of the T-ALL cell line LOUCY) tumors with Venetoclax (ABT-199) 100 mg/kg for 4 days results in a significant reduction of leukemic burden^[2].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Essai clinique

Masse moléculaire

868.44

Formule

C₄₅H₅₀ClN₇O₇S

CAS No.

1257044-40-8

Appearance

Solid

Color

Light yellow to yellow

SMILES

O=C(NS(=O)(C1=CC=C(NCC2CCOCC2)C([N+]([O-])=O)=C1)=O)C3=CC=C(N4CCN(CC5=C(C6=CC=C(Cl)C=C6)CC(C)(C)CC5)CC4)C=C3OC7=CN=C(NC=C8)C8=C7

Livraison

Room temperature in continental US; may vary elsewhere.

Stockage

Powder	-20°C	3 years
	4°C	2 years
In solvent	-80°C	2 years
	-20°C	1 year

Solvant et solubilité

In Vitro:

DMSO : 77.5 mg/mL (89.24 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)

Ethanol : < 1 mg/mL (insoluble)

Preparing
Stock Solutions

Concentration Solvent Mass	1 mg	5 mg	10 mg

1 mM	1.1515 mL	5.7575 mL	11.5149 mL
5 mM	0.2303 mL	1.1515 mL	2.3030 mL
10 mM	0.1151 mL	0.5757 mL	1.1515 mL

View the Complete Stock Solution Preparation Table

* Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.

Calculateur de molarité
Calculateur de dilution

Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)

Concentration _(start) × Volume _(start) = Concentration _(final) × Volume _(final)

This equation is commonly abbreviated as: C₁V₁ = C₂V₂

Concentration _(start)

Volume _(start)

Concentration _(final)

Volume _(final)

In Vivo:

Select the appropriate dissolution method based on your experimental animal and administration route.

For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for in vivo experiments, it is recommended to prepare freshly and use it on the same day.
The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.

Protocol 1

Add each solvent one by one: 10% Ethanol 60% Phosal 50 PG 30% PEG400
Solubility: 20 mg/mL (23.03 mM); Suspended solution; Need ultrasonic
Protocol 2

Add each solvent one by one: 5% DMSO 40% PEG300 5% Tween-80 50% Saline
Solubility: 5 mg/mL (5.76 mM); Suspended solution; Need ultrasonic and warming and heat to 49°C
Protocol 3

Add each solvent one by one: 10% DMSO 40% PEG300 5% Tween-80 45% Saline
Solubility: 2.5 mg/mL (2.88 mM); Suspended solution; Need ultrasonic

This protocol yields a suspended solution of 2.5 mg/mL. Suspended solution can be used for oral and intraperitoneal injection.
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.
Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
Protocol 4

Add each solvent one by one: 10% DMSO 90% (20% SBE-β-CD in Saline)
Solubility: 2.5 mg/mL (2.88 mM); Suspended solution; Need ultrasonic and warming

This protocol yields a suspended solution of 2.5 mg/mL. Suspended solution can be used for oral and intraperitoneal injection.
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 900 μL 20% SBE-β-CD in Saline, and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C, storage for one week): 2 g SBE-β-CD powder is dissolved in 10 mL Saline, completely dissolve until clear.

For the following dissolution methods, please prepare the working solution directly. It is recommended to prepare fresh solutions and use them promptly within a short period of time.
The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.

Protocol 1

Add each solvent one by one: 45% PEG300 5% Tween-80 50% Saline
Solubility: 10 mg/mL (11.51 mM); Suspended solution; Need ultrasonic
Protocol 2

Add each solvent one by one: 15% Cremophor EL 85% Saline
Solubility: 10 mg/mL (11.51 mM); Suspended solution; Need ultrasonic

In Vivo Dissolution Calculator

Please enter the basic information of animal experiments:

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Dosing volume
(per animal)

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Number of animals

Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.

Please enter your animal formula composition:

DMSO +

Tween-80 +

Saline

Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.

The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).

Calculation results:

Working solution concentration: mg/mL

Method for preparing stock solution: mg drug dissolved in μL DMSO (Stock solution concentration: mg/mL).

The concentration of the stock solution you require exceeds the measured solubility. The following solution is for reference only. If necessary, please contact MedChemExpress (MCE).

Method for preparing in vivo working solution for animal experiments: Take μL DMSO stock solution, add μL . μL , mix evenly, next add μL Tween 80, mix evenly, then add μL Saline.

If the continuous dosing period exceeds half a month, please choose this protocol carefully.

Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.

Pureté et documentation

Purity: 99.95%

Select Batch:

SDS (558 KB)

COA (250 KB) HNMR (220 KB) LCMS (139 KB) Elemental Analysis Report (107 KB)

Instruction de manipulation (2659 KB)

Références

[1]. Souers AJ, et al. ABT-199, a potent and selective BCL-2 inhibitor, achieves antitumor activity while sparing platelets. Nat Med. 2013 Feb;19(2):202-8. [Content Brief]

[2]. Peirs S, et al. ABT-199 mediated inhibition of BCL-2 as a novel therapeutic strategy in T-cell acute lymphoblastic leukemia. Blood. 2014 Dec 11;124(25):3738-47. [Content Brief]

[3]. Bi C, et al. Inhibition of 4EBP phosphorylation mediates the cytotoxic effect of mechanistic target of rapamycin kinase inhibitors in aggressive B-cell lymphomas. Haematologica. 2017 Apr;102(4):755-764. [Content Brief]

Test cellulaire ^[1]	RS4;11 cells are seeded at 50,000 per well in 96-well plates and treated with compounds diluted in half-log steps starting at 1 μM and ending at 0.00005 μM. All other leukemia and lymphoma cell lines are seeded at 15,000-20,000 cells per well in the appropriate medium and incubated with Venetoclax or Navitoclax for 48 h. Effects on proliferation are determined using Cell TiterGlo reagent. EC₅₀ values are determined by nonlinear regression analysis of the concentration-response data. Mouse FL5.12-BCL-2 and FL5.12-BCL-XL cells are propagated and assessed. Bak^-/- Bax^-/- double knockout mouse embryonic fibroblasts are seeded into 96-well microtiter plates at 5,000 cells per well in DMEM supplemented with 10% FBS. Venetoclax (ABT-199) in the same culture medium is added in half-log dilutions starting at 5 μM. The cells are then incubated at 37°C (5% CO₂) for 48 h, and the effects on proliferation are determined using Cell TiterGlo reagent^[1]. MCE n'a pas confirmé de manière indépendante l'exactitude de ces méthodes. Ils sont pour référence seulement.
Administration animale ^[2]	Mice^[2] Nonobese diabetic/severe combined immunodeficient γ (NSG) mice are injected at 6 weeks of age in the tail vein with 150 µL phosphate-buffered saline containing 5×10⁶ luciferase-labeled LOUCY cells. At regular time points, the bioluminescence is measured using the IVIS Lumina II imaging system. At 6 weeks, the cells are engrafted and the mice are randomly divided into 2 groups (with an equal number of males and females in both groups), and the treatment is started on day 0. Mice are treated with Venetoclax (ABT-199) 100 mg/kg body weight or with vehicle via oral gavage for 4 consecutive days. At days 0, 2, and 4 the bioluminescene is measured. MCE n'a pas confirmé de manière indépendante l'exactitude de ces méthodes. Ils sont pour référence seulement.
Références	[1]. Souers AJ, et al. ABT-199, a potent and selective BCL-2 inhibitor, achieves antitumor activity while sparing platelets. Nat Med. 2013 Feb;19(2):202-8. [Content Brief] [2]. Peirs S, et al. ABT-199 mediated inhibition of BCL-2 as a novel therapeutic strategy in T-cell acute lymphoblastic leukemia. Blood. 2014 Dec 11;124(25):3738-47. [Content Brief] [3]. Bi C, et al. Inhibition of 4EBP phosphorylation mediates the cytotoxic effect of mechanistic target of rapamycin kinase inhibitors in aggressive B-cell lymphomas. Haematologica. 2017 Apr;102(4):755-764. [Content Brief]

Complete Stock Solution Preparation Table

Optional Solvent	Concentration Solvent Mass	1 mg	5 mg	10 mg	25 mg

DMSO	1 mM	1.1515 mL	5.7575 mL	11.5149 mL	28.7873 mL
	5 mM	0.2303 mL	1.1515 mL	2.3030 mL	5.7575 mL
	10 mM	0.1151 mL	0.5757 mL	1.1515 mL	2.8787 mL
	15 mM	0.0768 mL	0.3838 mL	0.7677 mL	1.9192 mL
	20 mM	0.0576 mL	0.2879 mL	0.5757 mL	1.4394 mL
	25 mM	0.0461 mL	0.2303 mL	0.4606 mL	1.1515 mL
	30 mM	0.0384 mL	0.1919 mL	0.3838 mL	0.9596 mL
	40 mM	0.0288 mL	0.1439 mL	0.2879 mL	0.7197 mL
	50 mM	0.0230 mL	0.1151 mL	0.2303 mL	0.5757 mL
	60 mM	0.0192 mL	0.0960 mL	0.1919 mL	0.4798 mL
	80 mM	0.0144 mL	0.0720 mL	0.1439 mL	0.3598 mL

Venetoclax Related Classifications

Apoptosis Autophagy
Bcl-2 Family Autophagy

Venetoclax [1257044-40-8]

Cat# HY-15531-10mg

Contatta il distributore locale :

Marca : MedChemExpress

Contatta il distributore locale :

Other Forms of Venetoclax:

Voir tous les produits spécifiques à Isoform Bcl-2 Family:

Calculateur de molarité

Calculateur de dilution

Complete Stock Solution Preparation Table

Venetoclax Related Classifications

Keywords:

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Venetoclax [1257044-40-8]

Cat# HY-15531-10mg

Contatta il distributore locale :

Marca : MedChemExpress

Contatta il distributore locale :

Other Forms of Venetoclax:

Voir tous les produits spécifiques à Isoform Bcl-2 Family:

Venetoclax Related Antibodies

Calculateur de molarité

Calculateur de dilution

Complete Stock Solution Preparation Table

Venetoclax Related Classifications

Keywords:

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