ABT-737

Alias: ABT 737; ABT-737; ABT737

Cat No.:V0002 Purity: ≥98%

COA Product Data Instructions for use SDS

ABT-737 is a novel, potent,selective and orally bioavailable BH3 mimetic inhibitor of Bcl-xL, Bcl-2 and Bcl-w with EC50 of 78.7 nM, 30.3 nM and 197.8 nM in enzymatic assays, respectively.

ABT-737 Chemical Structure CAS No.: 852808-04-9
Product category: Bcl-2

This product is for research use only, not for human use. We do not sell to patients.

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Other Forms of ABT-737:

ABT-737-d8

Official Supplier of:

Top Publications Citing lnvivochem Products

Nature 2021, 597(7874):119-125.

Cell 2020,183:1202-1218.e25.

Science Adv 2022: 8, eabm9427.

Nature 597, 119–125 (2021)

Cell Stem Cell 2020,26(6):845-861.e12.

Science Trans Med 2023,15(701):eadd7872.

STTT 2023,8(1):91.

Cell Reports 2023,42(4):112313

Science Trans Med 2023, 15: eadd7872.

Cancer Cell 2021,39(4):529-547.e7.

Cancer Discov 2022,12(4):1106-1127.

Immunity 2023,56(3):620-634.e11.

J Am Chem Soc 2022,144:21831-21836.

Cell 2020,183:1202-1218.e25.

Science Adv 2022:8,eabm9427.

Nature 2021,597(7874):119-125.

Cell 2020,183:1202-1218.e25.

PNAS Nexus 2022,1(3):pgac063.

ACS Nano 2023,17(10):9110-9125.

Biomaterial 2023 Sep16:302:122333.

Purity & Quality Control Documentation

Current batch：

Purity: ≥98%

COA

MSDS

NMR

Instructions

Product Description
Bioactivity & Protocols
Physicochemical Properties
Solubility Data
Calculators
Clinical Trial Information
Biological Data

Product Description

ABT-737 is a novel, potent, selective and orally bioavailable BH3 mimetic inhibitor of Bcl-xL, Bcl-2 and Bcl-w with EC50 of 78.7 nM, 30.3 nM and 197.8 nM in enzymatic assays, respectively. Mcl-1, Bcl-B, Bfl-1, etc. are not inhibited by it. It is currently undergoing a Phase 2 clinical trial to treat cancer. ABT-737 has demonstrated significant antimyeloma activity both in vitro and in vivo, as well as single-agent activity against lymphoma and small-cell lung cancer. ABT-737 works as a BCL-2 inhibitor by mimicking BH3, which is the native ligand of BCL-2. It prevents the anti-apoptotic BCL-2 protein, causing CLL cells to undergo programmed cell death.

Biological Activity I Assay Protocols (From Reference)

Targets

Bcl-2 (EC50=30.3 nM); Bcl-xL (EC50=78.7 nM); Bcl-W (EC50=197.8 nM); Bcl-B (EC50=1820 nM); Bfl-1 (EC50>10 μM); Mcl-1 (EC50>10 μM)

ln Vitro

ABT-737 binds to the antiapoptotic BCL-2 family members BCL-2, BCL-XL, and BCL-W with high affinity (Ki 1 nM), but weakly (Ki > 460 nM) to MCL-1 and BFL-1. The BH3-binding groove of BCL-XL and BCL-2 is bound by ABT-737[1]. ABT-737 (100 nM; 1-72 hours) induces apoptosis and synergizes with chemotherapy in HL-60 cells[1]. ABT-737 (5, 7.5, and 10 M; 72 h) kills 80% of the HCT116 cells. ABT-737 cannot harm the BAX knockout variant at all[1]. ABT-737 has no effect on cell cycle distribution. In HL-60 leukemic cells, ABT-737 prevents BCL-2/BAX heterodimerization and causes a change in BAX conformation[1]. IABT-737 induces a BAX/BAK-dependent impairment of maximal O2 consumption rate in sensitive cells. An ABT-737-sensitive primed for death state is induced by stable BCL-2 overexpression in MCF10A cells. In B-cell lymphoma cells, ABT-737 causes a dose-dependent impairment of the maximal oxygen consumption rate[3].

ln Vivo

ABT-737 (20, 30 mg/kg/day; i.p.; for 21 days) suppresses the leukemia burden by 48% and 53% at the 20 and 30 mg/kg dose levels, respectively, in four- to six-week-old CB.17 Scid mice were given KG-1 cells from human leukemia[1]. ABT-737 significantly extends survival of mice in this aggressive leukemia model[1].

Enzyme Assay

To determine the binding affinity of GST-BCL-2 family proteins to the FITC-conjugated BH3 domain of BIM (FITC-Ahx-DMRPEIWIAQELRRIGDEFNAYYAR), FPAs are performed as follows. Briefly, 100 nM of GST-BCL-2 family fusion proteins are incubated with serial dilutions of ABT-737 in PBS for 2 min. Then, 20 nM of FITC-BIM BH3 peptide (FITC-Ahx-DMRPEIWIAQELRRIGDEFNAYYAR) is added. Fluorescence polarization is measured using an Analyst TM AD Assay Detection System after 10 min using the 96-well black plate. IC50s are determined using GraphPad Prism software.

Cell Assay

Cells are treated with ABT-737, ABT-263, or vehicle (DMSO) for 4 h in XF24 assay medium (6×104 MCF10A cells, see medium composition below) or RPMI 1640 medium (1×106 B-cell lymphoma cells) and apoptosis is analyzed by Annexin-V-binding/PI exclusion or by sub-diploid nuclei determination. FACS analysis is performed on Becton Dickinson FACScan or FACScalibur instruments. Data analysis is performed with CellQuest software.

Animal Protocol

20 and 30 mg/kg

1 g/mL stock solution of ABT-737 in DMSO is added to a mixture of 30% propylene glycol, 5% Tween 80, 65% D5W (5% dextrose in water) (pH 4 5; final concentration of DMSO ≤ 1%)

Scid mice injected with Luc-expressing FD/ΔRaf-1:ER cells

References

[1]. Mechanisms of apoptosis sensitivity and resistance to the BH3 mimetic ABT-737 in acute myeloid leukemia. Cancer Cell. 2006 Nov;10(5):375-88.

[2]. Effect of dual inhibition of apoptosis and autophagy in prostate cancer. Prostate. 2012 Sep 1;72(12):1374-81.

[3]. Rapid Detection of an ABT-737-Sensitive Primed for Death State in Cells Using Microplate-Based Respirometry.PLoS One. 2012;7(8):e42487. Epub 2012 Aug 3.

These protocols are for reference only. InvivoChem does not independently validate these methods.

Physicochemical Properties

Molecular Formula

C42H45CLN6O5S2

Molecular Weight

813.43

Exact Mass

812.25814

Elemental Analysis

C, 62.02; H, 5.58; Cl, 4.36; N, 10.33; O, 9.83; S, 7.88

CAS #

852808-04-9

Related CAS #

ABT-737-d8;1217686-68-4

Appearance

Solid powder

SMILES

O=C(NS(=O)(C1=CC=C(N[C@H](CCN2CCOCC2)CSC3=CC=CC=C3)C(S(=O)(C(F)(F)F)=O)=C1)=O)C4=CC=C(N5CCN(CC6=C(C7=CC=C(Cl)C=C7)CCC(C)(C)C6)CC5)C=C4

InChi Key

HPLNQCPCUACXLM-PGUFJCEWSA-N

InChi Code

InChI=1S/C42H45ClN6O5S2/c1-46(2)23-22-35(30-55-37-9-4-3-5-10-37)44-40-21-20-38(28-41(40)49(51)52)56(53,54)45-42(50)32-14-18-36(19-15-32)48-26-24-47(25-27-48)29-33-8-6-7-11-39(33)31-12-16-34(43)17-13-31/h3-21,28,35,44H,22-27,29-30H2,1-2H3,(H,45,50)/t35-/m1/s1

Chemical Name

(R)-4-(4-((4'-chloro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-((4-(dimethylamino)-1-(phenylthio)butan-2-yl)amino)-3-nitrophenyl)sulfonyl)benzamide

Synonyms

ABT 737; ABT-737; ABT737

HS Tariff Code

2934.99.9001

Storage

Powder -20°C 3 years

4°C 2 years

In solvent -80°C 6 months

-20°C 1 month

Shipping Condition

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Solubility Data

Solubility (In Vitro)

DMSO: ~100 mg/mL (~122.9 mM)

Water: <1 mg/mL(slightly soluble or insoluble)

Ethanol: <1 mg/mL

Solubility (In Vivo)

30% Propylene glycol, 5% Tween 80, 65% D5W: 30mg/mL

(Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	1.2294 mL	6.1468 mL	12.2936 mL
	5 mM	0.2459 mL	1.2294 mL	2.4587 mL
	10 mM	0.1229 mL	0.6147 mL	1.2294 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.

Calculator

Mass

Concentration

Volume

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See Example

An example of molarity calculation using the molarity calculator is shown below:
What is the mass of compound required to make a 10 mM stock solution in 5 ml of DMSO given that the molecular weight of the compound is 350.26 g/mol?

Enter 350.26 in the Molecular Weight (MW) box
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The answer of 17.513 mg appears in the Mass box. In a similar way, you may calculate the volume and concentration.

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Dilution Calculator allows you to calculate how to dilute a stock solution of known concentrations. For example, you may Enter C1, C2 & V2 to calculate V1, as detailed below:

What volume of a given 10 mM stock solution is required to make 25 ml of a 25 μM solution?
Using the equation C1V1 = C2V2, where C1=10 mM, C2=25 μM, V2=25 ml and V1 is the unknown:

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The answer of 62.5 μL (0.1 ml) appears in the Volume (Start) box

Molecular formula

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Molecular Weight Calculator allows you to calculate the molar mass and elemental composition of a compound, as detailed below:

Note: Chemical formula is case sensitive: C12H18N3O4 c12h18n3o4
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Definitions of molecular mass, molecular weight, molar mass and molar weight:

Molecular mass (or molecular weight) is the mass of one molecule of a substance and is expressed in the unified atomic mass units (u). (1 u is equal to 1/12 the mass of one atom of carbon-12)
Molar mass (molar weight) is the mass of one mole of a substance and is expressed in g/mol.

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Reconstitution Calculator allows you to calculate the volume of solvent required to reconstitute your vial.

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The answer appears in the Volume (to add to vial) box

In vivo Formulation Calculator (Clear solution)

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

Dosage mg/kg

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Step 2: Enter in vivo formulation (This is only a calculator, not the exact formulation for a specific product. Please contact us first if there is no in vivo formulation in the solubility section.)

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Calculation results

Working concentration： mg/mL；

Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution 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 stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH₂O，mix and clarify.

Note： (1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.

Clinical Trial Information

NCT Number	Status	Interventions	Conditions	Sponsor/Collaborators	Start Date	Phases
NCT01440504	Completed	Other: culture ex vivo with exposure to different the rapeutic agents alone or in combination.	Ovarian Cancer	Centre Francois Baclesse	April 2010
NCT00902018	Completed	Drug: Eltrombopag Drug: Romiplostim Other: healthy controls	Immune Thrombocytopenia	Weill Medical College of Cornell University	January 2009	Phase 2

Biological Data

Whole cell lysates of Mel-RM and MM200 cells were subjected to Western blot analysis following treatment with ABT-737 (10µM) for indicated periods. Data are representative of three individual experiments.

As an inhibitor of Bcl-2, ABT-737 is effective to reduce cell viability in HG3-CLL cells. Incubating the cells with ABT-737 in 96 well plates (3×104 cells per well) for 24h shows a dose-dependent inhibition of cell viability with EC50 value of 500nM.