SAR405

• CAT Number: I001891
• CAS Number: 1523406-39-4
• Molecular Formula: C19H21ClF3N5O2
• Molecular Weight: 443.9
• Purity: ≥95%
• Target: Autophagy
• Solubility: DMSO：≥ 27 mg/mL
• Storage: Store at -20°C
• InChI: InChI=1S/C19H21ClF3N5O2/c1-12-11-30-5-4-26(12)16-7-17(29)27-3-2-15(19(21,22)23)28(18(27)25-16)10-13-6-14(20)9-24-8-13/h6-9,12,15H,2-5,10-11H2,1H3/t12-,15+/m1/s1
• InChIKey: SPDQRCUBFSRAFI-KEKZHRQWSA-N
• SMILES: C[C@H]1N(C(N=C2N3CC[C@@H](C(F)(F)F)N2CC4=CN=CC(Cl)=C4)=CC3=O)CCOC1

SAR405 (Cat.No:I001891) is a potent and selective inhibitor of class III phosphoinositide 3-kinase (PI3K), also known as Vps34. It plays a crucial role in autophagy, a cellular process that degrades and recycles damaged components. SAR405 has shown promise in preclinical studies as a valuable tool to investigate autophagy and may have implications in cancer and neurodegenerative disease research.

Reference

1:Autophagy. 2015 Apr 3;11(4):725-6. doi: 10.1080/15548627.2015.1033601. SAR405, a PIK3C3/Vps34 inhibitor that prevents autophagy and synergizes with MTOR inhibition in tumor cells.Pasquier B, PMID: 25905679 PMCID: PMC4502822 DOI: 10.1080/15548627.2015.1033601 Abstract: Autophagy plays an important role in cancer and it has been suggested that it functions not only as a tumor suppressor pathway to prevent tumor initiation, but also as a prosurvival pathway that helps tumor cells endure metabolic stress and resist death triggered by chemotherapeutic agents. We recently described the discovery of inhibitors of PIK3C3/Vps34 (phosphatidylinositol 3-kinase, catalytic subunit type 3), the lipid kinase component of the class III phosphatidylinositol 3-kinase (PtdIns3K). This PtdIns3K isoform has attracted significant attention in recent years because of its role in autophagy. Following chemical optimization we identified SAR405, a low molecular mass kinase inhibitor of PIK3C3, highly potent and selective with regard to other lipid and protein kinases. We demonstrated that inhibiting the catalytic activity of PIK3C3 disrupts vesicle trafficking from late endosomes to lysosomes. SAR405 treatment also inhibits autophagy induced either by starvation or by MTOR (mechanistic target of rapamycin) inhibition. Finally our results show that combining SAR405 with everolimus, the FDA-approved MTOR inhibitor, results in a significant synergy on the reduction of cell proliferation using renal tumor cells. This result indicates a potential therapeutic application for PIK3C3 inhibitors in cancer.