ZX-29

ZX-29 is a potent and selective ALK inhibitor with an IC50 of 2.1 nM, 1.3 nM and 3.9 nM for ALK, ALK L1196M and ALK G1202R mutations, respectively. ZX-29 is inactive against EGFR. ZX-29 induces apoptosis by inducing endoplasmic reticulum (ER) stress and overcomes cell resistance caused by an ALK mutation. ZX-29 also induces protective autophagy and has antitumor effect.

Product information

CAS Number: 2254805-62-2

Molecular Weight: 518.03

Formula: C23H28ClN7O3S

Chemical Name: N-{2-[(5-chloro-2-{[2-methoxy-4-(4-methylpiperazin-1-yl)phenyl]amino}pyrimidin-4-yl)amino]phenyl}methanesulfonamide

Smiles: CN1CCN(CC1)C1=CC(OC)=C(C=C1)NC1=NC(NC2=CC=CC=C2NS(C)(=O)=O)=C(Cl)C=N1

InChiKey: ATHZZWBANOJUOA-UHFFFAOYSA-N

InChi: InChI=1S/C23H28ClN7O3S/c1-30-10-12-31(13-11-30)16-8-9-20(21(14-16)34-2)27-23-25-15-17(24)22(28-23)26-18-6-4-5-7-19(18)29-35(3,32)33/h4-9,14-15,29H,10-13H2,1-3H3,(H2,25,26,27,28)

Technical Data

Appearance: Solid Power

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

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:

ZX-29 (0-81 nM; 24-72 hours; NCI-H2228 cells) treatment leads to a time- and dose-dependent decrease in NCI-H2228 cell viability. ZX-29 (10 nM; 24 hours; NCI-H2228 cells) treatment causes typical signs of autophagy and the formation of autophagosomes. ZX-29 enhances the expression level of LC3 and Beclin1. ZX-29 (10 nM; 0-48 hours; NCI-H2228 cells) inhibits the proliferation of NCI-H2228 cells and arrests the cells in G1 phase. ZX-29 (10-40 nM; 24-48 hours; NCI-H2228 cells) treatment induces apoptosis of NCI-H2228 cells. ZX-29 dose-dependently upregulates the expression levels of proapoptotic protein Bax, increases the production of activated forms of caspase 3, and downregulates the expression level of antiapoptotic protein Bcl-2. ZX-29 (30-300 nM; 24 hours; NCI-H2228 cells) treatment significantly down-regulates the expression of p-ALK and its downstream signaling proteins, including p-Akt and p-STAT3, in a dose-dependent manner. ZX-29 (20 nM; 0-48 hours; NCI-H2228 cells) treatment significantly increases the mRNA level of CHOP. ZX-29 dose-dependently inhibits colony formation of NCI-H2228 cells. With an increase in ZX-29 concentration, the cell density decreased gradually, and the cells lost their normal morphology and become sharp and slender.

In Vivo:

ZX-29 (50 mg/kg; intragastric administration; every 2 days; for a total of 7 times; female BALB/c nude mice) treatment suppresses tumor growth in a mouse xenograft model.

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