WDR5-IN-4 (Compound C6) is a WIN site inhibitor of chromatin-associated WD repeat domain 5 protein ( WDR5 ), K d The value is 0.1 nM. WDR5-IN-4 is able to displace WDR5 from chromatin and reduce the expression of related genes, causing translation inhibition and nucleolar stress. Has anti-cancer effects [1] [1].
In Vivo, WDR5-IN-4 (100 μg, intrauterine injection, single dose) promotes Hox genes in hindbrains of the Rnf220+/- mice at late embryonic stages[2].
In Vitro, WDR5-IN-4 (0-50 μM, 3 days) inhibits the proliferation of MLL1-rearranged cancer cells MV4:11 and K562 cells with GI50s of 3.20 μM and 25.4 μM[1]. WDR5-IN-4 (2 μM, 6 days) arrests the cell cycle of MV4:11 at sub-G1 phase, induces apoptosis in MV4:11[1].
References:
[1]. Aho ER, et al. Displacement of WDR5 from Chromatin by a WIN Site Inhibitor with Picomolar Affinity. Cell Rep. 2019 Mar 12;26(11):2916-2928.e13.
[2]. Wang H, et al. The E3 ubiquitin ligase RNF220 maintains hindbrain Hox expression patterns through regulation of WDR5 stability[J]. Elife, 2024, 13: RP94657.
In Vivo, WDR5-IN-4 (100 μg, intrauterine injection, single dose) promotes Hox genes in hindbrains of the Rnf220+/- mice at late embryonic stages[2].
In Vitro, WDR5-IN-4 (0-50 μM, 3 days) inhibits the proliferation of MLL1-rearranged cancer cells MV4:11 and K562 cells with GI50s of 3.20 μM and 25.4 μM[1]. WDR5-IN-4 (2 μM, 6 days) arrests the cell cycle of MV4:11 at sub-G1 phase, induces apoptosis in MV4:11[1].
References:
[1]. Aho ER, et al. Displacement of WDR5 from Chromatin by a WIN Site Inhibitor with Picomolar Affinity. Cell Rep. 2019 Mar 12;26(11):2916-2928.e13.
[2]. Wang H, et al. The E3 ubiquitin ligase RNF220 maintains hindbrain Hox expression patterns through regulation of WDR5 stability[J]. Elife, 2024, 13: RP94657.