WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 205889
CAS#: 1116743-46-4
Description: SAR125844 is a potent and highly selective c-Met inhibitor with potential antineoplastic activity. Upon intravenous administration, SAR125844 binds to c-Met, thereby disrupting c-Met-mediated signal transduction pathways. SAR125844 displayed nanomolar activity against the wild-type kinase (IC50 value of 4.2 nmol/L) and the M1250T and Y1235D mutants. Broad biochemical profiling revealed that SAR125844 was highly selective for MET kinase. SAR125844 inhibits MET autophosphorylation in cell-based assays in the nanomolar range, and promotes low nanomolar proapoptotic and antiproliferative activities selectively in cell lines with MET gene amplification or pathway addiction.
MedKoo Cat#: 205889
Name: SAR125844
CAS#: 1116743-46-4
Chemical Formula: C25H23FN8O2S2
Exact Mass: 550.1369
Molecular Weight: 550.6314
Elemental Analysis: C, 54.53; H, 4.21; F, 3.45; N, 20.35; O, 5.81; S, 11.64
Synonym: SAR125844; SAR 125844; SAR-125844
IUPAC/Chemical Name: 1-(6-((6-(4-fluorophenyl)-[1,2,4]triazolo[4,3-b]pyridazin-3-yl)thio)benzo[d]thiazol-2-yl)-3-(2-morpholinoethyl)urea
InChi Key: ODIUNTQOXRXOIV-UHFFFAOYSA-N
InChi Code: InChI=1S/C25H23FN8O2S2/c26-17-3-1-16(2-4-17)19-7-8-22-30-31-25(34(22)32-19)37-18-5-6-20-21(15-18)38-24(28-20)29-23(35)27-9-10-33-11-13-36-14-12-33/h1-8,15H,9-14H2,(H2,27,28,29,35)
SMILES Code: O=C(NC1=NC2=CC=C(C=C2S1)SC3=NN=C4C=CC(C5=CC=C(C=C5)F)=NN43)NCCN6CCOCC6
Appearance: Solid powder
Purity: >98% (or refer to the Certificate of Analysis)
Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility: Soluble in DMSO, not in water
Shelf Life: >2 years if stored properly
Drug Formulation: This drug may be formulated in DMSO
Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code: 2934.99.9001
The following data is based on the product molecular weight 550.6314 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass | 1 mg | 5 mg | 10 mg |
|---|---|---|---|
| 1 mM | 1.15 mL | 5.76 mL | 11.51 mL |
| 5 mM | 0.23 mL | 1.15 mL | 2.3 mL |
| 10 mM | 0.12 mL | 0.58 mL | 1.15 mL |
| 50 mM | 0.02 mL | 0.12 mL | 0.23 mL |
1. Anti-tumoral composition comprising the compound 1-(6-{[6-(4-fluorophenyl)[1,2,4]triazolo[4,3-b]pyridazin-3-yl]sulfanyl}-1,3-benzothiazol-2-yl)-3-(2-morpholin-4-ylethyl)urea. By Authelin, Jean-Rene; Assadourian, Sylvie; Benard, Tsiala; Goulaouic, Helene; Mathieu, Amandine; Peracchia, Maria-Teresa From PCT Int. Appl. (2014), WO 2014009500 A1 20140116.
2. Egile C, Kenigsberg M, Delaisi C, Bégassat F, Do-Vale V, Mestadier J, Bonche F, Bénard T, Nicolas JP, Valence S, Lefranc C, Francesconi E, Castell C, Lefebvre AM, Nemecek C, Calvet L, Goulaouic H. The selective intravenous inhibitor of the MET tyrosine kinase SAR125844 inhibits tumor growth in MET-amplified cancer. Mol Cancer Ther. 2015 Feb;14(2):384-94. doi: 10.1158/1535-7163.MCT-14-0428. Epub 2014 Dec 10. PubMed PMID: 25504634.
Activation of the MET/HGF pathway is common in human cancer and is thought to promote tumor initiation, metastasis, angiogenesis, and resistance to diverse therapies. We report here the pharmacologic characterization of the triazolopyridazine derivative SAR125844, a potent and highly selective inhibitor of the MET receptor tyrosine kinase (RTK), for intravenous administration. SAR125844 displayed nanomolar activity against the wild-type kinase (IC50 value of 4.2 nmol/L) and the M1250T and Y1235D mutants. Broad biochemical profiling revealed that SAR125844 was highly selective for MET kinase. SAR125844 inhibits MET autophosphorylation in cell-based assays in the nanomolar range, and promotes low nanomolar proapoptotic and antiproliferative activities selectively in cell lines with MET gene amplification or pathway addiction. In two MET-amplified human gastric tumor xenograft models, SNU-5 and Hs 746T, intravenous treatment with SAR125844 leads to potent, dose- and time-dependent inhibition of the MET kinase and to significant impact on downstream PI3K/AKT and RAS/MAPK pathways. Long duration of MET kinase inhibition up to 7 days was achieved with a nanosuspension formulation of SAR125844. Daily or every-2-days intravenous treatment of SAR125844 promoted a dose-dependent tumor regression in MET-amplified human gastric cancer models at tolerated doses without treatment-related body weight loss. Our data demonstrated that SAR125844 is a potent and selective MET kinase inhibitor with a favorable preclinical toxicity profile, supporting its clinical development in patients with MET-amplified and MET pathway-addicted tumors. (see: Mol Cancer Ther. 2015 Feb;14(2):384-94. doi: 10.1158/1535-7163.MCT-14-0428. Epub 2014 Dec 10.).
