SGX-523

Name: SGX-523
Brand: Selleck Chemicals
SKU: S1112
Rating: 5 (16 reviews)

For research use only. Not for use in humans.

Catalog No.S1112

16 publications

Molecular Weight(MW): 359.41

SGX-523 is a selective Met inhibitor with IC50 of 4 nM, no activity to BRAFV599E, c-Raf, Abl and p38α. Phase 1.

Selleck's SGX-523 has been cited by 16 publications

Nat Commun, 2019, 10(1):2701

PubMed: 31221965 ( click the link to review the publication )

Cell Rep, 2019, 28(9):2331-2344

PubMed: 31461650 ( click the link to review the publication )

Cancer Res, 2018, 78(15):4360-4369

PubMed: 29844123 ( click the link to review the publication )

Sci Rep, 2018, 8(1):11894

PubMed: 30089804 ( click the link to review the publication )

Sci Rep, 2018, 8(1):1955

PubMed: 29386539 ( click the link to review the publication )

Am J Respir Crit Care Med, 2016, 10.1164/rccm.201509-1878OC

PubMed: 26959387 ( click the link to review the publication )

Nat Commun, 2016, 7:10690

PubMed: 26891683 ( click the link to review the publication )

Acta Pharmacol Sin, 2016, 37(12):1587-1596

PubMed: 27616574 ( click the link to review the publication )

Int J Oncol, 2015, 47(1):71-80

PubMed: 25955301 ( click the link to review the publication )

J Hepatol, 2014, 60(1):143-51

PubMed: 23978713 ( click the link to review the publication )

Clin Cancer Res, 2013, 19(9):2584-91

PubMed: 23515407 ( click the link to review the publication )

Biomarkers, 2013, 18(2):126-35

PubMed: 23410046 ( click the link to review the publication )

Proc Natl Acad Sci USA, 2012, 109(31):E2127-33

PubMed: 22773810 ( click the link to review the publication )

Neuro Oncol, 2012, 15(2):161-71

PubMed: 23258844 ( click the link to review the publication )

Mol Cell Proteomics, 2012, 11(6):M112.017764

PubMed: 22345495 ( click the link to review the publication )

Neoplasia, 2011, 13(12):1132-42

PubMed: 22241959 ( click the link to review the publication )

4 Customer Reviews

Association of c-Met phosphorylation and s-Met generation in EBC-1 xenograft tumor. Mice were treated with SGX523 at 10 mg/kg, 3 mg/kg, 0.1 mg/kg, at 0 h and 8 h point, respectively. Plasma and tumor lysates were collected using the method described in "Materials and methods"section at 24 h time point. The bar and line in the figure represents the average phosphorylation rate of c-Met and s-Met in subgroups, respectively. Each subgroup consists of four mice with tumor volume around 600 mm³.

Biomarkers 2013 18(2), 126-35. SGX-523 purchased from Selleck.
After starved in serum-free medium for 24h, Breast cancer cells incubated with the indicated concentrations of SGX-523 for 3h,followed by 15-minute stimolation of 100ng/ml HGF.

Dr. Zhang of Tianjin Medical University. SGX-523 purchased from Selleck.
Sci Rep, 2018, 8(1):1955. SGX-523 purchased from Selleck.
Effects of indicated compounds on modulation of protein expression. HCC827/GR6, NCI-H1650, and NCI-H1975 cells were treated with the indicated compounds for 24 h and analyzed by Western blotting.

Acta Pharmacol Sin, 2016, 37(12):1587-1596. SGX-523 purchased from Selleck.

Purity & Quality Control

Choose Selective c-Met Inhibitors

Biological Activity

Description

SGX-523 is a selective Met inhibitor with IC50 of 4 nM, no activity to BRAFV599E, c-Raf, Abl and p38α. Phase 1.

Targets

c-Met ^[1]
(Cell-free assay)

4 nM

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]

Protocol

Kinase Assay:^[1]	- Collapse 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 μL) are quenched with 20 μL Kinase-Glo detection buffer. Luminescence is detected in a plate-reading luminometer and the results are analyzed by nonlinear regression.
Cell Research:^[1]	- Collapse Cell lines: MDCK cells Concentrations: 200 nM Incubation Time: 18 hours Method: MDCK cells are seeded at 1 × 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 × 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-fou (Only for Reference)
Animal Research:^[1]	- Collapse Animal Models: GTL16, U87, or H441 xenografts in Harlan nude mice Formulation: 0.5% MC 400 with 0.05% Tween 80 Dosages: 60 mg/kg Administration: Oral gavage (Only for Reference)

References

[1] Buchanan SG, et al. Mol Cancer Ther, 2009, 8(12), 3181-3190.

Solubility (25°C)

In vitro	DMSO	3 mg/mL warmed (8.34 mM)
	Water	Insoluble
	Ethanol	Insoluble
In vivo	Add solvents to the product individually and in order(Data is from Selleck tests instead of citations): 0.5% methylcellulose+0.2% Tween 80 For best results, use promptly after mixing.	30 mg/mL

* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

Chemical Information Download SGX-523 SDF

Molecular Weight	359.41
Formula	C₁₈H₁₃N₇S
CAS No.	1022150-57-7
Storage	3 years -20°C powder
Storage	2 years -80°C in solvent
Synonyms	N/A
Smiles	C[N]1C=C(C=N1)C2=N[N]3C(=NN=C3C=C2)SC4=CC=C5N=CC=CC5=C4

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Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

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c-Met Signaling Pathway Map

c-Met Inhibitors with Unique Features

Non-specific c-Met Inhibitor

BMS-777607 : C-Met, IC50=3.9 nM；Axl, IC50=1.1 nM; Ron, IC50=1.8 nM; Tyro3, IC50=4.3 nM.
Most Potent c-Met Inhibitor

INCB28060 : C-Met, IC50=0.13 nM.
FDA-approved c-Met Inhibitor

Crizotinib (PF-02341066) : Approved by FDA for non-small cell lung carcinoma (NSCLC).
Newest c-Met Inhibitor

EMD 1214063 ^New : Potent and selective c-Met inhibitor with IC50 of 4 nM, >200-fold selective for c-Met than IRAK4, TrkA, Axl, IRAK1, and Mer.

Related c-Met Products

NPS-1034 ^New

NPS-1034 is a dual Met/Axl inhibitor with IC50 of 48 nM and 10.3 nM, respectively.
Erlotinib ^New

Erlotinib is an EGFR inhibitor with IC50 of 2 nM, >1000-fold more sensitive for EGFR than human c-Src or v-Abl.
Bemcentinib（R428) ^New

R428 (BGB324) is an inhibitor of Axl with IC50 of 14 nM, >100-fold selective for Axl versus Abl. Selectivty for Axl is also greater than Mer and Tyro3 (50-to-100- fold more selective) and InsR, EGFR, HER2, and PDGFRβ (100- fold more selective).
Crizotinib (PF-02341066)

Crizotinib (PF-02341066) is a potent inhibitor of c-Met and ALK with IC50 of 11 nM and 24 nM in cell-based assays, respectively. It is also a potent ROS1 inhibitor with Ki value less than 0.025 nM.
Foretinib (GSK1363089)

Foretinib (GSK1363089) is an ATP-competitive inhibitor of HGFR and VEGFR, mostly for Met and KDR with IC50 of 0.4 nM and 0.9 nM in cell-free assays. Less potent against Ron, Flt-1/3/4, Kit, PDGFRα/β and Tie-2, and little activity to FGFR1 and EGFR. Phase 2.
Capmatinib (INCB28060)

Capmatinib (INCB28060) is a novel, ATP-competitive inhibitor of c-MET with IC50 of 0.13 nM in a cell-free assay, inactive against RONβ, as well as EGFR and HER-3. Phase 1.

Features:Inactive against RONβ, another member of the c-MET RTK family, as well as EGFR and HER-3 (members of the EGFR RTK family).
Tivantinib (ARQ 197)

Tivantinib (ARQ 197) is the first non-ATP-competitive c-Met inhibitor with K_i of 0.355 μM in a cell-free assay, little activity to Ron, and no inhibition to EGFR, InsR, PDGFRα or FGFR1/4. Phase 3.

Features:The first selective c-Met inhibitor to be advanced into human clinical trials.
PHA-665752

PHA-665752 is a potent, selective and ATP-competitive c-Met inhibitor with IC50 of 9 nM in cell-free assays, >50-fold selectivity for c-Met than RTKs or STKs.
BMS-777607

BMS-777607 is a Met-related inhibitor for c-Met, Axl, Ron and Tyro3 with IC50 of 3.9 nM, 1.1 nM, 1.8 nM and 4.3 nM in cell-free assays, 40-fold more selective for Met-related targets versus Lck, VEGFR-2, and TrkA/B, and more than 500-fold greater selectivity versus all other receptor and non receptor kinases. Phase 1/2.

Features:A potent inhibitor of the Met family, and >40-fold selectivity vs. Lck, VEGFR2, and TrkA/B and >500-fold selective vs. other receptor and non-receptor kinases.
PF-04217903

PF-04217903 is a selective ATP-competitive c-Met inhibitor with IC50 of 4.8 nM in A549 cell line, susceptible to oncogenic mutations (no activity to Y1230C mutant). Phase 1.

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SGX-523