SAR125884 hydrochlorid (1116743-46-4(free base))

SKU: orb1301593

Description

SAR125844 is a highly potent and selective inhibitor of the MET kinase, demonstrating an IC50 of 4.2 nM. It has shown a favorable preclinical safety profile and is a valuable tool compound for investigating MET-driven cancers in both cellular and animal model studies.

Research Area

Signal Transduction

Key Properties

• MW: 587
• Purity: 97.95% (May vary between batches)
• Formula: C₂₅H₂₃FN₈O₂S₂.HCl
• SMILES: Cl.Fc1ccc(cc1)-c1ccc2nnc(Sc3ccc4nc(NC(=O)NCCN5CCOCC5)sc4c3)n2n1
• Target: c-Met/HGFR
• Solubility: DMSO:55 mg/mL (93.7 mM)

Bioactivity

• Target IC50:
  MET RTK:4.2 nM
• In Vivo:
  SAR125844 inhibited autophosphorylation of AXL and cell proliferation of TPM–NTRK1-overexpressing KM12 cell line with IC50 values of 110 and 1,400 nmol/L, respectively, indicating a 30- and 500-fold selectivity index for AXL and NTRK1 in cell-based assays. The selectivity profile of SAR125844 was further confirmed in cell lines with a single-digit nanomolar antiproliferative activity in MET-addicted cell lines and a complete lack of impact in cells not addicted to the MET pathway. This is in contrast to ARQ197 that has equal antiproliferative activity on MET-addicted and MET-independent tumor cell lines.
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• In Vitro:
  MKN-45, Hs 746T, and SNU-5 cells were seeded in poly d-lysine 96-well plates in complete medium. Plates were incubated with increasing SAR125844 concentrations for 1 hour, cell lysates were generated using standard procedures and pMETY1230/1234/1235 level evaluated. IC50 values were calculated using the software and a 4-parameter logistic model.
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• Animal Research:
  The antitumor activity of SAR125844 was investigated after administration of SAR125844 solution daily in SNU-5 bearing mice at 10, 20, and 45 mg/kg and every 2 days in Hs 746T tumor–bearing mice (at 5, 10, 20, and 45 mg/kg for SAR125844 solution and at 5, 11, 21, 53, 106, and 213 mg/kg for SAR125844 nanosuspension). Tumor volumes (in mm^3, based on the following formula, volume = length (mm) × width2 (mm2)/2), were measured twice weekly and body weight recorded every day. Endpoints collected were complete regressions (CR, regression below the palpable limit), partial regressions (PR, regression of 50% of the initial tumor volume), and the percentage of tumor regression (% of volume decrease posttreatment compared with pretreatment). Statistical significance was determined by a Dunnett test versus vehicle after a two-way ANOVA with repeated measures performed separately on ranks of changes from baseline with P < 0.05 considered significant.
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Storage & Handling

• Storage: -20°C
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

SAR125884 hydrochlorid (1116743 46 4(free base)), SAR125884 hydrochlorid (1116743464(free base)), SAR-125884 hydrochlorid (1116743-46-4(free base)), SAR125884 hydrochlorid (1116743-46-4(free base)), cMet, c-Met, cMet/HGFR, HGFR, MET RTK

Compound Identifiers

PubChem CID

154578321