ZW4864 - CAS# 2632259-93-7

ZW4864 is an orally active and selective β catenin/B-Cell lymphoma 9 protein protein interaction (β catenin/BCL9 PPI) inhibitor. ZW4864 inhibits β catenin/BCL9 PPI with a Ki value of 0.76 μM and an IC50 value of 0.87 μM.

Product information

CAS Number: 2632259-93-7

Molecular Weight: 607.19

Formula: C33H43ClN6O3

Chemical Name: 4-(2-{3-[(3R)-3-[cyclopropyl({[4-(1H-pyrazol-4-yl)phenyl]methyl})carbamoyl]piperidin-1-yl]phenoxy}-2-methylpropanoyl)piperazin-1-ium chloride

Smiles: [Cl-].CC(C)(OC1=CC(=CC=C1)N1C[C@@H](CCC1)C(=O)N(CC1C=CC(=CC=1)C1=CNN=C1)C1CC1)C(=O)N1CC[NH2+]CC1

InChiKey: PQRRIGABHUYXRQ-UFTMZEDQSA-N

InChi: InChI=1S/C33H42N6O3.ClH/c1-33(2,32(41)37-17-14-34-15-18-37)42-30-7-3-6-29(19-30)38-16-4-5-26(23-38)31(40)39(28-12-13-28)22-24-8-10-25(11-9-24)27-20-35-36-21-27;/h3,6-11,19-21,26,28,34H,4-5,12-18,22-23H2,1-2H3,(H,35,36);1H/t26-;/m1./s1

Technical Data

Appearance: Solid Power

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

Solubility: DMSO : 41.67 mg/mL (68.63 mM; ultrasonic and warming and heat to 60°C; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO).

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:

ZW4864 (10~40 μM; 24 hours; SW480 and MBA-MD-231 cells) decreases the expression levels of Axin2 and cyclin D1 proteins. ZW4864 (10~40 μM; 72 hours; MDA-MB231, MCF10A and MDA-MB-468 cells) selectively triggeres rapid apoptosis of triple-negative breast cancer cells with hyperactive β-catenin signaling while sparing normal mammary epithelial MCF10A cells. ZW4864 (10~40 μM; 24 hours; SW480 and MBA-MD-231 cells) suppresses the transcription of β-catenin target genes in a concentration-dependent manner without affecting the expression of HPRT, a house-keeper gene, in both SW480 and Wnt 3a-activated MDA-MB-231 cells. ZW4864 binds with β-catenin and selectively disrupts the protein protein interaction (PPI) between B-cell lymphoma 9 (BCL9) and β-catenin while sparing the β-catenin/E-cadherin PPI. ZW4864 dose-dependently suppresses β-catenin signaling activation, downregulates oncogenic β-catenin target genes, and abrogates invasiveness of β-catenin-dependent cancer cells. ZW4864 suppresses TOPFlash luciferase activities in β-catenin expressing HEK293 cells in a dose-dependent manner with an IC50 of 11 μM. ZW4864 also dose-dependently suppresses the TOPFlash luciferase activities in SW480 and Wnt 3a-activated MDA-MB-468 cells with the IC50s of 7.0 and 6.3 μM, respectively. ZW4864 selectively suppresses transactivation of β-catenin signaling.

In Vivo:

ZW4864 (20 mg/kg; p.o.) exhibits good pharmacokinetic properties with an oral bioavailability (F) of 83 %. ZW4864 (90 mg/kg; p.o.) shows a variation in tumor growth in mice. ZW4864 shows good pharmacokinetic properties and effectively suppresses β-catenin target gene expression in the patient-derived xenograft mouse model.

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