产品
编 号:F762438
分子式:C45H51N11O9
分子量:889.95
产品类型
结构图
CAS No: 2417408-46-7
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产品详情
生物活性:
YX-2-107 is a PROTAC (IC50= 4.4 nM) that selectively degrades CDK6. YX-2-107 effectively inhibits RB phosphorylation and FOXM1 expression in vitro and inhibits the development of Ph+ ALL in rats. YX-2-107 can be used in the study of Ph chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL).
体内研究:
YX-2-107 (10 mg/kg; i.p.; single) 显示最大浓度为 741 nM (比 CDK6 降解 IC50 高 150 倍),4 小时后从血浆中清除。YX-2-107 (150 mg/kg; i.p.; single daily for 3 days) 在抑制大鼠体内 Ph+ ALL 增殖中具有药理学活性。Animal Model:NRG-SGM3 mice (Ph+ ALL xenografts model).
Dosage:150 mg/kg
Administration:Intraperitoneal injection; single daily for 3 days
Result:Suppressed the percentage of primary Ph+ ALL S-phase cells, the expression of CDK4/6-regulated phospho-RB and, to a lesser degree, FOXM1, and induced the selective CDK6 degradation.
Animal Model:C57BL/6j mice.
Dosage:10 mg/kg
Administration:Intraperitoneal injection; single
Result:1.19Pharmacokinetic Parameters of YX-2-107in C57BL/6j mice . IP (10 mg/kg)
Tmax (h)0.5
Cmax (ng/mL)660
AUC0-t (ng/mL·h)815
AUC0-∞ (ng/mL·h)987
体外研究:
YX-2-107 (2000 nM; 48 h) 在 Ph 染色体阳性 (Ph+) 的 BV173 和 SUP-B15 细胞中,显示抑制 S 期活性。YX-2-107 (0, 1.6, 8, 40, 200, 1000 nM; 4 h) 在 BV173 细胞中,能选择性降解 CDK6。YX-2-107 (2000 nM; 72 h) 在 Ph 染色体阳性 (Ph+) 的 BV173 和 SUP-B15 细胞中,抑制 RB 磷酸化和 FOXM1 表达。