| Bioactivity | 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]. |
| Invitro | 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 pSTAT5Y694 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 pSTAT5Y694 的水平[1]。 Western Blot Analysis[1] Cell Line: |
| In Vivo | 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 pSTAT5Y694 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 (Vz=2.1 L/kg)[1]。 Animal Model: |
| Name | AK-2292 |
| Formula | C52H54F2N7O10PS2 |
| Molar Mass | 1070.13 |
| Transport | Room temperature in continental US; may vary elsewhere. |
| Storage | Please store the product under the recommended conditions in the Certificate of Analysis. |
| Reference | [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. [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. |