RVL-101

RVL-101 is a preclinical, small molecule inhibitor of cyclin-dependent kinase 4 (CDK4) developed by Reverie Labs. It is characterized by a novel pharmacophore that provides high selectivity for CDK4 while sparing CDK2, CDK6, CDK7, and CDK9, and maintaining over 500-fold selectivity over CDK1. A key differentiator of RVL-101 is its superior central nervous system (CNS) penetration, achieving high free-brain levels (Kpu,u = 0.7), which addresses the limited brain penetration of existing CDK4/6 inhibitors. Preclinical data demonstrate efficacy in ER+/HER2- and HR-/HER2+ breast cancer models, as well as glioblastoma (GBM) models, both as a monotherapy and in combination with agents such as tucatinib, fam-trastuzumab-deruxtecan, and temozolomide.