MS67 T39976

Product Introduction
Bioactivity


英文名: MS67

描述: MS67 is a potent and selective degrader of the WD40 repeat domain protein 5 (WDR5) with a dissociation constant (Kd) of 63 nM. It exhibits no activity against protein methyltransferases, kinases, G-protein-coupled receptors (GPCRs), ion channels, and transporters. Notably, MS67 demonstrates significant anticancer properties.

体外活性: MS67 (0.001-1 μM) induces WDR5 degradation at a concentration as low as 1 nM. MS67 induces WDR5 depletion much more effectively in all six mixed lineage leukemia (MLL)-r acute myeloid leukemia (AML) and four pancreatic ductal adenocarcinoma (PDAC) cell lines without a hook effect and in a concentration-dependent manner in PDAC cells[1]. MS67 decreases H3K4me2/3 in both MV4;11 and MIA PaCa-2 cells, whereas other examined histone methylation marks such as H3K9me3, H3K27me3, and H3K36me3 are not affected . MS67 is effective in suppressing both WDR5-related gene expression programs and WDR5/MLL-induced H3K4 methylations on chromatin[1]. The GI 50 values of MS67 in the two most sensitive AML lines, MV4;11 and EOL-1, are 15 nM and 38 nM, respectively. MLL-r acute leukemia cell lines including MV4;11, EOL-1, MOLM13, KOPN8, RS4;11, and THP-1 are sensitive to MS67, whereas leukemia cell lines that did not harbor MLL-r (including K562, HL60, and a murine AML line transformed by Hoxa9 plus Meis1) are insensitive to MS67[1]. .MS67 binds to VCB (VHL-Elongin C-Elongin B ternary complex), with a K d of 140 nM[1]. Western Blot Analysis[1]Cell Line: MV4;11 cells Concentration: 0.001 μM, 0.005 μM, 0.01 μM, 0.05 μM, 0.1 μM, 0.5 μM, 1 μM Incubation Time: 18 hours Result: Induced WDR5 degradation at a concentration as low as 1 nM with DC 50 of 3.7 nM.

体内活性: MS67 (75 mg/kg; i.p.; twice daily; 5 days a week; for 20 days) significantly inhibits tumor growth in vivo and prolongs survival of the treated mice[1]. After a single intraperitoneal (i.p.) injection of MS67 at a dose of 75 mg/kg, the Cmax reached at about 4.2 μM, and the concentration of MS67 retained above 0.5 μM over 12 hours[1]. Animal Model: MV4;11 MLL-r AML xenograft mouse[1]Dosage: 75 mg/kg Administration: i.p.; twice daily; 5 days a week; for 20 days Result: Inhibited tumor growth in vivo.

存储条件: Powder: -20°C for 3 years | In solvent: -80°C for 1 year

关键字: MS67 | MS-67 | MS 67

MS67 T39976信息由TargetMol中国为您提供，如您想了解更多关于MS67 T39976报价、型号、参数等信息，欢迎来电或留言咨询。

注：该产品未在中华人民共和国食品药品监督管理部门申请医疗器械注册和备案，不可用于临床诊断或治疗等相关用途