WS-383 是一种有效、选择性、可逆的 DCN1-UBC12 相互作用抑制剂，IC50 值为 11 nM。WS-383 抑制 Cul3/1 的类泛素化修饰，引起 p21，p27 和 NRF2 的积累。
货号:ajcx38668
CAS:2247544-02-9
分子式:C18H21Cl2N9S2
分子量：498.46
溶解度:DMSO : 7.35 mg/mL (14.75 mM; Need ultrasonic)
纯度：98%
存储：Store at -20°C
库存：现货

Background:

WS-383 is a potent, selective and reversible inhibitor of DCN1-UBC12 interaction, with an IC50 of 11 nM. WS-383 inhibits Cul3/1 neddylation, induces accumulation of p21, p27 and NRF2[1].

WS-383 (10 μM) is against a panel of kinases such as BTK, CDKs, and EGFR [L858R] using staurosporine and BIBW 2992 as the positive controls. WS-383 showed weak inhibitory activity at 10.0 μM,it is selective to the DCN1-UBC12 interaction over the selected kinasesr[1].
WS-383 (0.03-3 μM;24 hours) blocks Cul3 neddylation at 3 μM and also has certain inhibition of Cul1 neddylation at 10 μM but was not effective in inhibiting neddylation of other cullin members[1].
WS-383 (0.03-3 μM;24 hours) increases Cul1, Skp1 (adaptor protein), F-box protein, and RBX1/RBX2 RING protein form SCF E3 complex. Cyclin dependent kinase inhibitor 1A (p21) and cyclin dependent kinase inhibitor 1B (p27) expression in a dose-dependent manner in MGC-803 and KYSE70 manner[1].

[1]. Wang S, et al. Development of Highly Potent, Selective, and Cellular Active Triazolo[1,5- a]pyrimidine-Based Inhibitors Targeting the DCN1-UBC12 Protein-Protein Interaction. J Med Chem. 2019 Mar 14;62(5):2772-2797.