SJ988497 是一种 PROTAC JAK2 降解剂。SJ988497 可有效地抑制 CRLF2 重排 (CRLF2r) 细胞的增殖并降解 CRBN 新底物 GSPT1。SJ988497 由 Ruxolitinib (HY-50856) 衍生物、连接子和 CRBN 配体 Pomalidomide 组成。 SJ988497 可用于急性淋巴细胞白血病 (ALL) 的研究。
| 生物活性 | SJ988497 is aPROTACJAK2degrader. SJ988497 potently inhibits CRLF2-rearranged (CRLF2r) cell proliferation and degrades the CRBN neosubstrate GSPT1. SJ988497 consists of aRuxolitinib(HY-50856) derivative, linker, and CRBN ligand Pomalidomide. SJ988497 can be used in the research of acute lymphoblastic leukemia (ALL)[1]. |
| IC50& Target[1] | |
体外研究
(In Vitro) | SJ988497 (compound 7) 在 Caco-2 测定实验中增加细胞渗透性，表观渗透系数 (Papp) 为 19.12 nm/s[1]。
SJ988497 抑制 parental MHH-CALL-4 细胞活力，EC50为 0.4 nM，抑制 MHH-CALL-4 细胞的 EC50为 3456.2 nM，这种抑制作用可以被 30 μMLenalidomide(HY-A0003) 阻断[1].
SJ988497 (1 h, 1 μM) 在 MHH-CALL-4 细胞中产生 JAK 抑制作用[1]。
Cell Viability Assay[1] | Cell Line: | NAL M6, MHH-CALL-2, 697, KOPN49, KOPN75, MHH-CALL-4 cells | | Concentration: | 0.01 nM-100 nM | | Incubation Time: | 72 h | | Result: | Dose-dependently inhibited cell viability in ALL cell lines. |
Western Blot Analysis[1] | Cell Line: | MHH-CALL-4 cells | | Concentration: | 1 nM, 10 nM, 100 nM, 1 μM, 4 μM. | | Incubation Time: | 1 h | | Result: | Degraded multiple JAKs (JAK1>JAK3>JAK2>TYK2), and was abolished by knockdown of CRBN. |
|
体内研究
(In Vivo) | SJ988497 (compound 7) (30 mg/kg，腹腔注射) 可减小脾脏大小和肿瘤负荷，并且耐受性良好，不会减轻体重或扰乱血细胞计数[1]。
SJ988497 (10-100 mg/kg, 腹腔注射, 每天两次) 显示出持续的体内暴露，24 小时后血浆浓度高于细胞实验中 50% 有效浓度值[1].
| Animal Model: | NSG mice inoculated by CL20SF2-Luc2aYFP cell (i.v.)[1] | | Dosage: | 30 mg/kg | | Administration: | Intraperitoneal injection (i.p.) | | Result: | Reduced leukemia burden in bone marrow, blood, and spleen, as well as total body bioluminescent imaging. |
|
| 分子量 | |
| Formula | |
| CAS 号 | |
| 运输条件 | Room temperature in continental US; may vary elsewhere. |
| 储存方式 | Please store the product under the recommended conditions in the Certificate of Analysis. |
m.cnreagent.com