WEHI-539 HCl

WEHI-539 HCl (WEHI-539 hydrochloride) has high affinity (IC50=1.1 nM) and selectivity for BCL-XL and potently kills cells by selectively antagonizing its prosurvival activity. It has more than a 400-fold higher affinity for BCL-XL versus other prosurvival BCL-2 family members.

Product information

CAS Number: 2070018-33-4

Molecular Weight: 620.18

Formula: C31H30ClN5O3S2

Synonym:

WEHI-539 hydrochloride

Chemical Name: 4-Thiazolecarboxylic acid, 5-[3-[4-(aminomethyl)phenoxy]propyl]-2-[8-[2-(2- benzothiazolyl)hydrazinylidene]-5,6,7,8-tetrahydro-2-naphthalenyl]-, hydrochloride (1:1)

Smiles: Cl.NCC1C=CC(=CC=1)OCCCC1SC(=NC=1C(O)=O)C1=CC2/C(/CCCC=2C=C1)=N/NC1=NC2=CC=CC=C2S1

InChiKey: GJBYTVIQTMIXGA-DYICZVFTSA-N

InChi: InChI=1S/C31H29N5O3S2.ClH/c32-18-19-10-14-22(15-11-19)39-16-4-9-27-28(30(37)38)34-29(40-27)21-13-12-20-5-3-7-24(23(20)17-21)35-36-31-33-25-6-1-2-8-26(25)41-31;/h1-2,6,8,10-15,17H,3-5,7,9,16,18,32H2,(H,33,36)(H,37,38);1H/b35-24+;

Technical Data

Appearance: Solid Power

Purity: ≥98% (or refer to the Certificate of Analysis)

Solubility: DMSO 100 mg/mL (161.24 mM)

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥12 months if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined

HS Tariff Code: 382200

How to use

In Vitro:

WEHI-539 shows good selectivity for BCL-XL. The tight ligand WEHI-539 retains this selectivity (500-fold over BCL-2 and 400-fold over BCL-W, MCL-1 and A1). WEHI-539 kills fibroblasts that lack MCL-1. Thus, WEHI-539 not only binds very tightly to BCL-XL, with IC50 and KD values close to or below 1 nM as well as a slow dissociation rate, but also invokes apoptotic responses that depend on BAX, BAK or both; furthermore, its biological activity is related to its binding profile, as elevated amounts of MCL-1, BCL-2 and BCL-W confer marked resistance, and its ability to destroy platelets is a well-validated marker of on-target BCL-XL inhibition. In addition, WEHI-539 induces a preferentially BAK-dependent apoptotic response in MEFs by selectively inhibiting BCL-XL.

References:

1. Lessene G, et al. Nat Chem Biol, 2013, 9(6), 390-397.

Products are for research use only. Not for human use.