| Bioactivity | DDO-2728 (compound 19) is a selective AlkB homologue 5 (ALKBH5) inhibitor with an IC50 of 2.97 μM. DDO-2728 increases the abundance of N6 methyladenosine (m6A) modifications, inducing cell apoptosis and cycle arrest. DDO-2728 suppresses tumor growth in the MV4−11 xenograft model with favorable safety profile, shows the potential of targeting ALKBH5 in cancer research[1]. |
| Target | AlkB homologue 5 (ALKBH5) IC50: 2.97 μM |
| Invitro | DDO-2728 (0-40 μM, 48 h) 在浓度梯度上提高 MOLM-13、HEK293 和 MV4-11 细胞的 m6A 甲基化水平[1]。DDO-2728 (0.01-100 μM, 72 h) 可抑制 MOLM-13 和 MV4-11 细胞的增殖，IC50s 分别为 0.45 和 1.2 μM，且对 HEK293 和 HUVEC 的毒性相对较弱[1]。DDO-2728 (20 μM, 48 h) 显著阻滞 MOLM-13 和 MV4-11 细胞的细胞周期于 G1/M 期[1]。DDO-2728 (5, 10 μM, 48 h) 浓度依赖性地诱导 MV4−11 和 MOLM-13 细胞凋亡[1]。DDO-2728 (20 μM, 24 h) 降低了 MOLM-13 和 MV4−11 细胞中 TACC3 mRNA 的半衰期[1]。DDO-2728 (0-10 μM, 48 h) 在 mRNA 和蛋白水平上显著降低 MOLM-13 和 MV4-11 细胞中 TACC3 和 c-Myc 的丰度[1]。1.19大鼠和人血浆与肝脏微粒体代谢稳定性[1]Species |
| In Vivo | DDO-2728 (10-40 mg/kg, 腹腔注射, 每日一次, 14 d) 可有效抑制 MV4−11 异种移植裸鼠的肿瘤生长[1]。1.19DDO-2728在大鼠体内的药动学参数[1]Parameter |
| Name | DDO-2728 |
| Formula | C28H17F3N4O7 |
| Molar Mass | 578.45 |
| 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]. Zheng-Yu Jiang, et al. Discovery of Pyrazolo[1,5-a]pyrimidine Derivative as a Novel and Selective ALKBH5 Inhibitor for the Treatment of AML. Journal of Medicinal Chemistry. 2023，Article ASAP. |