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COH000

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Chemical Structure| 1534358-79-6 同义名 : -
CAS号 : 1534358-79-6
货号 : A1145658
分子式 : C25H25NO5
纯度 : 99%+
分子量 : 419.47
MDL号 : MFCD31807643
存储条件：

粉末 Keep in dark place,Sealed in dry,2-8°C

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 35 mg/mL(83.44 mM)，配合低频超声助溶，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO
动物实验配方：
生物活性
描述 COH000 is a highly specific covalent allosteric inhibitor of SUMO E1 with little ability to inhibit other canonical Ubl E1s, including Uba1, Uba6, Nedd8 E1 or the noncanonical Ubl E1, Uba5. COH000 inhibited the ATP-dependent step of SUMO E1 catalysis and inhibited SUMOylation with an average IC50 of approximately 0.2μM in vitro, but did not inhibit ubiquitylation in a Ubc13-mediated poly-ubiquitylation assay tested under the same condition at concentrations up to 100μM, with over 500-fold selectivity for SUMOylation than ubiquitylation. COH000 at concentration ranging in 2-16μM inhibited SUMO E1-catalyzed Ubc9-SUMO thioester formation in a dose-dependent manner. It increased the degradation of SAE2 in pulse-chase assays, likely because the inactive conformation enhanced ubiquitin-proteasome-mediated degradation. COH000 at concentration of 10 and 20μM inhibited SUMOylation in HCT-116 cells in a dose-dependent manner upon 18-hour treatment.
作用机制 COH000 targets a cryptic binding pocket on SUMO E1 and exploits conformational coupling of SUMO E1 domains.[1]
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

2.38mL

0.48mL

0.24mL

11.92mL

2.38mL

1.19mL

23.84mL

4.77mL

2.38mL
参考文献

[1]Lv Z, Yuan L, et al. Molecular mechanism of a covalent allosteric inhibitor of SUMO E1 activating enzyme. Nat Commun. 2018 Dec 4;9(1):5145.

[2]Li YJ, Du L, et al. Allosteric Inhibition of Ubiquitin-like Modifications by a Class of Inhibitor of SUMO-Activating Enzyme. Cell Chem Biol. 2019 Feb 21;26(2):278-288.e6.