AK-2292 

AK-2292 is a potent and selective STAT5 PROTAC degrader, with a DC₅₀ of 0.10 μM. AK-2292 induces degradation of STAT5A/B proteins in vitro and in vivo. AK-2292 can induce tumor regression in acute myeloid leukemia and chronic myeloid leukemia xenograft mouse models^[1][2]. AK-2292 is a click chemistry reagent, it contains an Alkyne group and can undergo copper-catalyzed azide-alkyne cycloaddition (CuAAc) with molecules containing Azide groups.

AK-2292 (0.0015-15 μM; 4 days) 抑制 SKNO1，MV4;11 和 Kasumi-3 细胞的生长，IC₅₀ 值分别为 0.36，0.35 和 0.18 μM ^[1]。
AK-2292 (0.008-5 μM; 18 h) 降低 SKNO1 细胞系中 STAT5A，STAT5B 和 pSTAT5^Y694 蛋白的水平^[1]。
AK-2292 (0.008-5 μM; 6 h) 有效降低 MV4;11 急性白血病细胞系中 STAT5 和 pSTAT5^Y694 的水平^[1]。

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

AK-2292 (50-200 mg/kg; i.p. once a day, 5 days a week for 3 weeks) 抑制小鼠 MV4;11 异种移植模型中的肿瘤生长^[1]。
AK-2292 (150 mg/kg; a single i.p.) 诱导小鼠 MV4;11 异种移植组织中的 STAT5 和 pSTAT5^Y694 蛋白 >95% 的快速消耗^[1]。
AK-2292 (i.p.) 表现出良好的血浆暴露，血浆半衰期为 1.9 h，清除率适中 (CL=0.77 L/h/kg)，体积分布良好 (V_z=2.1 L/kg)^[1]。

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

1070.13

C₅₂H₅₄F₂N₇O₁₀PS₂

2984506-77-4

固体

Off-white to light yellow

Room temperature in continental US; may vary elsewhere.

4°C, stored under nitrogen

*In solvent : -80°C, 6 months; -20°C, 1 month (stored under nitrogen)

• [1]. Kaneshige A, et, al. Discovery of a Potent and Selective STAT5 PROTAC Degrader with Strong Antitumor Activity In Vivo in Acute Myeloid Leukemia. J Med Chem. 2023 Feb 3.  [Content Brief]

  [2]. Kaneshige A, et, al. A selective small-molecule STAT5 PROTAC degrader capable of achieving tumor regression in vivo. Nat Chem Biol. 2023 Feb 2.  [Content Brief]