Reziciclideg (BTX-9341) is a potent, seletive, blood-brain barrier permeable cereblon-mediated bifunctional degrader of CDK4 and CDK6 with Kd of 31 nM (CDK6), DC50 of <1 nM (Dmax>85%)
BTX-9341 is more selective than the CDK4/6i palbociclib at 100 nM, and proteomics indicates minimal off-target degradation.
BTX-9341 is blood-brain barrier permeable and shows sustained intracranial exposure for more than 12 hours.
BTX-9341 functionally inhibits cell proliferation in multiple GBM cell lines with IC50s in the nanomolar range.
BTX-9341 inhibits Rb phosphorylation in different GBM cell lines with pRb IC50s below 10 nM.
BTX-9341 induces cell cycle arrest at low nanomolar concentrations in GBM cell lines.
BTX-9341 exhibits dose dependent tumor growth inhibition in U-87 intracranial xenograft model (MGMT-negative), shows superior survival as compared to abemaciclib and Palbociclib.
BTX-9341 inhibits tumor growth in U-118 xenograft model (MGMT-positive).