YX-2-107 is a selective and potent CDK6-degrading PROTAC with an IC50 value of 4.4 nM.YX-2-107 inhibits RB phosphorylation and FOXM1 expression in vitro, and inhibits the development of Ph+ ALL in rats.YX-2-107 can be used for the prophylaxis and treatment of Ph chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL). YX-2-107 can be used for the prevention and treatment of Ph chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL).

CDK6:4.4 nM

In Ph+ BV173 and SUP-B15 cells, YX-2-107, when applied at a concentration of 2000 nM for 48 hours, demonstrates inhibition of the S phase[1]. Furthermore, at various concentrations (0, 1.6, 8, 40, 200, 1000 nM) for 4 hours, YX-2-107 selectively degrades CDK6 in BV173 cells[1]. Additionally, when used at a concentration of 2000 nM for 72 hours, YX-2-107 inhibits RB phosphorylation and FOXM1 expression in Ph+ BV173 and SUP-B15 cells[1].

Following a single intraperitoneal administration at a dose of 10 mg/kg, YX-2-107 achieves a maximum concentration of 741 nM in plasma after 4 hours. This concentration is 150-fold greater than the CDK6 degradation IC50. Clearance from the plasma is observed within the mentioned timeframe[1]. Moreover, when administered at a dose of 150 mg/kg intraperitoneally, once daily for 3 days, YX-2-107 is pharmacologically active in suppressing the proliferation of Ph+ ALL in mice[1].