MS67 是一种有效的选择性 WD40 重复域蛋白 5 (WDR5) 降解剂，Kd为 63 nM。MS67 对其他蛋白质甲基转移酶、激酶、GPCR、离子通道和转运蛋白无活性。MS67 显示出有效的抗癌作用。
| 生物活性 | MS67 is a potent and selectiveWD40 repeat domain protein 5 (WDR5)degrader with aKdof 63 nM. MS67 is inactive against other protein methyltransferases, kinases, GPCRs, ion channels, and transporters. MS67 shows potent acticancer effects[1]. |
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体外研究
(In Vitro) | 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 GI50values 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].
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MS67 binds to VCB (VHL-Elongin C-Elongin B ternary complex), with a Kdof 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 DC50of 3.7 nM. |
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体内研究
(In Vivo) | 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. |
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| 运输条件 | Room temperature in continental US; may vary elsewhere. |
| 储存方式 | -20°C, sealed storage, away from moisture *In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture) |
| 溶解性数据 | In Vitro: DMSO : 100 mg/mL(97.07 mM;ultrasonic and warming and heat to 60℃) 配制储备液 | 1 mM | 0.9707 mL | 4.8537 mL | 9.7074 mL | | 5 mM | 0.1941 mL | 0.9707 mL | 1.9415 mL | | 10 mM | 0.0971 mL | 0.4854 mL | 0.9707 mL |
*请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。
储备液的保存方式和期限：-80℃, 6 months; -20℃, 1 month (sealed storage, away from moisture)。-80℃ 储存时，请在 6 个月内使用，-20℃ 储存时，请在 1 个月内使用。 |
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