NDI-091143

NDI-091143 is a small molecule inhibitor of ATP-citrate lyase (ACLY), an enzyme that catalyzes the conversion of citrate to acetyl-CoA and oxaloacetate. This step is crucial for de novo lipogenesis, which is frequently upregulated in various cancers to support membrane synthesis and signaling. Developed by Nimbus Therapeutics, NDI-091143 has demonstrated the ability to synergize with B-Raf inhibitors, such as vemurafenib, to reduce cell viability and induce apoptosis in Ras-mutant cancer cells, including those from melanoma, breast, pancreatic, and colon tumors. The mechanism involves the activation of the ER stress pathway and caspase-3-dependent apoptosis.