MS67

发表于由

上海金畔生物科技有限公司为生命科学和医药研发人员提供生物活性分子抑制剂、激动剂、特异性抑制剂、化合物库、重组蛋白，专注于信号通路和疾病研究领域。

MS67 

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。

MS67

MS67 Chemical Structure

CAS No. : 2407452-77-9

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生物活性

MS67 is a potent and selective WD40 repeat domain protein 5 (WDR5) degrader with a Kd of 63 nM. MS67 is inactive against other protein methyltransferases, kinases, GPCRs, ion channels, and transporters. MS67 shows potent acticancer effects[1].

IC50 & Target[1]

VHL

 

WDR5

63 nM (Kd)

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 GI50 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 Kd of 140 nM[1].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

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 DC50 of 3.7 nM.

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].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

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.

分子量

1030.14

Formula

C52H59F4N9O7S
CAS 号

2407452-77-9
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.
参考文献

  • [1]. Xufen Yu, et al. A selective WDR5 degrader inhibits acute myeloid leukemia in patient-derived mouse models. Sci Transl Med. 2021 Sep 29;13(613):eabj1578.

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