CLS-189

CLS-189 (also known as CLS189) is an orally bioavailable, small-molecule inhibitor of hematopoietic prostaglandin D2 synthase (HPGDS) being developed by the University of Queensland for the treatment of Duchenne muscular dystrophy (DMD). It was optimized from the predecessor tool compound PK007 to achieve improved potency and pharmacokinetic properties. By selectively inhibiting HPGDS, CLS-189 blocks the synthesis of pro-inflammatory prostaglandin D2 (PGD2) while maintaining or upregulating beneficial prostaglandins (such as PGE2, PGI2, and PGF2α) that support muscle regeneration and recovery. In preclinical studies using the mdx mouse model of DMD, oral administration of CLS-189 significantly improved muscle grip strength and reduced myonecrosis and fibrotic area in hindlimb muscles, demonstrating superior potency and oral exposure compared to the clinical-stage HPGDS inhibitor TAS-205.