SGX-523

Item no.	S1112-1000
Manufacturer	Selleckchem
CASRN	1022150-57-7
Amount	1 g
Quantity options	10 mg 1 g 10 g 25 mg 5 mg 50 mg 5 g
Category	Oncology Inhibitors & Compound Libraries Small Molecules By Organ Lung Cancer Colorectal Cancer Breast Cancer Brain Cancer
Type	Inhibitors
Specific against	other
Smiles	CN1C=C(C=N1)C2=NN3C(=NN=C3SC4=CC5=C(C=C4)N=CC=C5)C=C2
ECLASS 10.1	32160490
ECLASS 11.0	32160490
UNSPSC	12000000
Alias	1022150-57-7'
Similar products	SGX-523
Available
Manufacturer - Targets	MET
Storage Conditions	2 years -80 in solvent
Molecular Weight	359, 41
Administration	Oral gavage
Animal Models	GTL16, U87, or H441 xenografts in Harlan nude mice
Cell lines	MDCK cells
Clinical Trials	A phase I clinical trial of SGX523 for the treatment of advanced cancer has been completed.
Concentrations	200 nM
Dosages	60 mg/kg
Formulation	0.5% MC 400 with 0.05% Tween 80
IC50	4 nM [1], 4 nM [1], 4 nM [1], 4 nM [1], 4 nM [1], 4 nM [1]
In vitro	SGX-523 belongs to the class of c-Met/hepatocyte growth factor receptor (HGFR) tyrosine kinase inhibitors. SGX-523 stabilizes MET in a unique inactive conformation that is inaccessible to other protein kinases, suggesting an explanation for its selectivity. SGX523 potently inhibits the purified MET catalytic domain but not the closely related receptor tyrosine kinase RON. SGX523 indicates ATP-competitive inhibition with higher apparent affinity for the less active, unphosphorylated form of MET [MET-KD(0P), with a Ki of 2.7 nM] versus the more active phospho-enzyme [MET-KD(3P), with a Ki of 23 nM], a phenomenon consistent with preferential binding to an inactive enzyme conformation. SGX523 inhibits MET-mediated signaling, cell proliferation and cell migration at nanomolar concentrations but had no effect on signaling dependent on other protein kinases, including the closely related RON, even at micromolar concentrations.[1]
In vivo	SGX523 significantly retards the growth of preestablished GTL16 tumors when administered orally at doses of >=10 mg/kg twice daily., SGX523 potently inhibits U87MG tumor growth, at 30 mg/kg dosed twice daily, SGX523 leads to clear regression of U87MG tumors. SGX523, dosed twice daily at 30 mg/kg, also retards the growth of H441 tumors with concomitant reduction in tumor MET autophosphorylation levels. SGX523 inhibition of MET in vivo is associated with the dose-dependent inhibition of growth of tumor xenografts derived from human glioblastoma, lung and gastric cancers, confirming the dependence of these tumors on MET catalytic activity. [1]
Incubation Time	18 hours
Kinase Assay	Kinase assays, Initial rate constants are measured at 21 C in the presence of 100 mM HEPES (pH 7.5), 0.3 mg/mL poly(Glu-Tyr) peptide substrate, 10 mM MgCl2, 1 mg/mL bovine serum albumin, 5% DMSO, 20 nM MET-KD and various concentrations of ATP and SGX523. Total reaction volumes (20 uL) are quenched with 20 uL Kinase-Glo detection buffer. Luminescence is detected in a plate-reading luminometer and the results are analyzed by nonlinear regression.
Method	MDCK cells are seeded at 1 x 103 per well in a 24-well plate and incubated at 37 C in 5% CO2 for 1 week in MEM and 10% fetal bovine serum. HGF (90 ng/mL) and various concentrations of SGX523 are added and the cells are incubated for another 18 hours (37 C, 5% CO2 humidified incubator) and visualized. A549 cells are plated in 12-well plates (6 x 104 per well) and incubated to confluence to investigate cell migration. A channel is introduced into the monolayers by scratching with a pipette tip. Various dilutions of compound are added in starve medium in the presence and absence of HGF (90 ng/mL).The wells are checked for cell migration after twenty-four hours.
Solubility (25C)	DMSO 2 mg/mL, Water <1 mg/mL, Ethanol <1 mg/mL
Information	SGX-523 is a selective Met (c-Met) inhibitor with IC50 of 4 nM, no activity to BRAFV599E, c-Raf, Abl and p38α. Phase 1.
Chemical Name	6-(6-(1-methyl-1H-pyrazol-4-yl)-[1, 2, 4]triazolo[4, 3-b]pyridazin-3-ylthio)quinoline

Note: The presented information and documents (Manual, Product Datasheet, Safety Datasheet and Certificate of Analysis) correspond to our latest update and should serve for orientational purpose only. We do not guarantee the topicality. We would kindly ask you to make a request for specific requirements, if necessary.

All products are intended for research use only (RUO). Not for human, veterinary or therapeutic use.

Request Data Sheet

S1112-1000-datasheet.pdf

S1112-1000-safety-datasheet.pdf