MAK1400

MAK1400 is an orally available small molecule inhibitor of N-acylethanolamine-hydrolyzing amidase (NAAA), currently in preclinical development by MAK Scientific. NAAA is a cysteine hydrolase enzyme primarily responsible for the degradation of palmitoylethanolamide (PEA), an endogenous lipid mediator that possesses potent anti-inflammatory and analgesic properties. By inhibiting NAAA, MAK1400 prevents the breakdown of PEA, thereby enhancing its protective signaling and modulating the endocannabinoid system. This mechanism is being explored for the treatment of inflammatory pain, neuropathic pain, and neuroinflammatory disorders such as multiple sclerosis, offering a potential therapeutic route that avoids the central nervous system side effects often associated with direct cannabinoid receptor ligands.