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SAR131675

CAS No. : 1433953-83-3

MCE 国际站：SAR131675

产品活性：SAR131675是有效，选择性的 VEGFR3 抑制剂，IC₅₀ 值为23 nM。

研究领域：Protein Tyrosine Kinase/RTK

作用靶点：VEGFR

In Vitro: AR131675 is highly selective for VEGFR-3. However, it is moderately active on VEGFR-2 with a VEGFR-3/VEGFR-2 ratio of about 10. SAR131675 inhibits VEGFR-3 tyrosine kinase activity and VEGFR-3 autophosphorylation in HEK cells with IC₅₀ values of 20 and 45 nM, respectively. SAR131675 dose dependently inhibits the proliferation of primary human lymphatic cells, induced by the VEGFR-3 ligands VEGFC and VEGFD, with an IC₅₀ of about 20 nM. SSAR131675 has no antiproliferative activity on a panel of 30 tumors and primary cells, further showing its high specificity and indicating that SAR131675 is not a cytotoxic or cytostatic agent.

In Vivo: SAR131675 is very well tolerated in mice and shows a potent antitumoral effect in several orthotopic and syngenic models, including mammary 4T1 carcinoma and RIP1.Tag2 tumors. Interestingly, it significantly reduces lymph node invasion and lung metastasis, showing its antilymphangiogenic activity in vivo. SAR131675 significantly reduces TAM infiltration and aggregation in 4T1 tumors. Despite the promising findings, SAR131675 development was terminated during preclinical development due to adverse metabolic effects.

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