ZLDI-8

ZLDI-8 is a Notch activating/cleaving enzyme ADAM-17 inhibitor and inhibits the cleavage of Notch protein. ZLDI-8 decreases the expression of pro-survival/anti-apoptosis and epithelial-mesenchymal transition (EMT) related proteins. ZLDI-8 is also a competitive and irreversible tyrosine phosphatase (Lyp) inhibitor with an IC50 of 31.6 μM and a Ki of 26.22 μM. ZLDI-8 inhibits the growth of MHCC97-H cells with an IC50 of 5.32 μM.

Product information

CAS Number: 667880-38-8

Molecular Weight: 433.52

Formula: C24H23N3O3S

Chemical Name: 5-({1-[2-(2, 4-dimethylphenoxy)ethyl]-2-methyl-1H-indol-3-yl}methylidene)-2-sulfanylidene-1, 3-diazinane-4, 6-dione

Smiles: CC1=CC(C)=C(C=C1)OCCN1C2=CC=CC=C2C(C=C2C(=O)NC(=S)NC2=O)=C1C

InChiKey: GNBZGGYWSRGVBG-UHFFFAOYSA-N

InChi: InChI=1S/C24H23N3O3S/c1-14-8-9-21(15(2)12-14)30-11-10-27-16(3)18(17-6-4-5-7-20(17)27)13-19-22(28)25-24(31)26-23(19)29/h4-9,12-13H,10-11H2,1-3H3,(H2,25,26,28,29,31)

Technical Data

Appearance: Solid Power

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

Solubility: DMSO : 62.5 mg/mL (144.17 mM; Need ultrasonic)

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: ≥360 days 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:

ZLDI-8 (0.03-30 μM; 6-72 hours; MHCC97-H cells) treatment reduces cell viability in a time- and dose-dependent manner. ZLDI-8 (1-10 μM; 6-72 hours; MHCC97-H cells) significantly decreases the level of NICD and the accumulation of NICD in the nucleus. ZLDI-8 could also reduce the expression of pro-survival/anti-apoptosis regulators, Survivin and cIAP1/2. And also increases the expression of epithelial marker E-Cadherin and reduced mesenchymal markers N-Cadherin and Vimentin. ZLDI-8 enhances chemotherapy effects on tumor cell proliferation blockage, induction of apoptosis and cell-cycle arrest by inhibiting Notch pathway and blocking chemical resistance.

In Vivo:

ZLDI-8 (0.2-2 mg/kg; intraperitoneal injection; every two days; for 20 days; nude mice) treatment enhances the effect of Sorafenib on inhibiting tumor growth in nude HCC-bearing mice model.

References:

1. Zhang Y, et al. Novel ADAM-17 inhibitor ZLDI-8 enhances the in vitro and in vivo chemotherapeutic effects of Sorafenib on hepatocellular carcinoma cells. Cell Death Dis. 2018 Jul 3;9(7):743.
2. Hou X, et al. Fast identification of novel lymphoid tyrosine phosphatase inhibitors using target-ligand interaction-based virtual screening. J Med Chem. 2014 Nov 26;57(22):9309-22.

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