fasn-in-3

FASN-IN-3 is an inhibitor of fatty acid synthase (FASN).

Octyl Orlistat, a potential fatty acid synthase (FASN) inhibitor, has demonstrated significant effectiveness in reducing tumor cell proliferation. By targeting FASN and inducing apoptosis, Orlistat is under investigation as an anti-tumor compound. Compared to Cerulenin and C75, Orlistat shows greater inhibitory potency in cell culture and cell lines. In LN229 cells, treatment with 200 µM Orlistat for 48 hours resulted in a 63.9 ± 8.7% reduction in cell growth, while in LT68 cells, the reduction was 76.3 ± 23.7%. Organotypic slice cultures treated with Orlistat exhibited decreased proliferation after Ki67 staining and an increase in caspase-3 cleavage.

CTL-06, a Fatty Acid Synthase (FASN) inhibitor with an IC50 of 3 μM, induces apoptosis, while CTL-12 impedes cell cycle progression in the Sub-G1 S phase and modulates apoptotic and anti-apoptotic markers by upregulating caspase-9 and Bax and downregulating Bcl-xL. Additionally, CTL-12 suppresses de novo lipogenesis, curtailing the metabolic needs of tumor cells, with utilization in breast and colorectal cancer studies [1].

Fasnall, a fatty acid synthase (FASN) inhibitor, exhibits an IC50 of 3.71 μM against the human recombinant enzyme. It halts tritiated acetate incorporation into lipids (IC50= 5.84 μM), boosts ceramide levels, and triggers lipid droplet formation in BT474 HER2+ breast cancer cells. Demonstrating antiproliferative effects on various breast cancer cell lines, including non-tumorigenic MCF-10A and tumorigenic MCF-7, MDA-MB-468, BT474, and SK-BR-3, its efficacy is directly linked to FASN expression in vitro. In murine models of HER2+ breast cancer, particularly the MMTV-Neu model, Fasnall significantly reduces tumor volume and extends survival. Furthermore, it enhances the efficacy of carboplatin in vivo, bolstering the objective response rate of stable disease from 25% with carboplatin alone to 88% when paired with Fasnall.