To assess the degradation of IRAK4 in PBMCs. Results showed that KT-474 robustly decreased IRAK4 levels in all immune cell types.
J Invest Dermatol. 2025 Feb;145(2):323-333.e10.
Monocytes
500 nM
20 hours
To assess the effect of KT-474 on IRAK4 degradation and cytokine production in monocytes. Results showed that KT-474 decreased IRAK4 protein levels and inhibited inflammatory cytokine production.
J Invest Dermatol. 2025 Feb;145(2):323-333.e10.
PBMCs
300 nM
24 hours
To evaluate the degradation selectivity of KT-474 across the proteome. Results showed that IRAK4 was the only protein significantly downregulated.
J Med Chem. 2024 Oct 24;67(20):18022-18037.
PBMCs
300 nM
24 hours
To assess the selectivity of KT-474 in human PBMCs. Results showed that KT-474 is selective for IRAK4.
Nat Med. 2023 Dec;29(12):3127-3136.
PBMCs
1 nM (DC50), 30 nM (DC90)
24, 48, 72, 96 hours
To assess IRAK4 degradation in PBMCs. Results showed maximal degradation of IRAK4 in PBMCs is achieved by 24 hours, with sustained degradation over 96 hours (Max. degradation ~90% compared to DMSO control).
Emily Lurier etal.
B cells
0.12-2000 nM
16 hours
To assess the inhibitory effect of KT-474 on NF-κB activation in CpG-B stimulated B cells. Results showed that KT-474 inhibited NF-κB activation, whereas PF-06550833 had no effect.
Nat Med. 2023 Dec;29(12):3127-3136
peripheral blood mononuclear cells (PBMCs)
300 nM
24 hours
To evaluate the selective degradation of IRAK4 by KT-474. Results showed that KT-474 selectively degraded IRAK4 without affecting other known immune-mediated inflammatory disease substrates.
Nat Med. 2023 Dec;29(12):3127-3136
KT-474 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
Mice
Imiquimod induced mouse model of psoriasis
Oral
30 mg/kg and 100 mg/kg
Twice a day for 3 days
To assess the anti-inflammatory efficacy of 17 in an imiquimod-induced mouse model of psoriasis. Results showed potent anti-inflammatory efficacy, comparable to topical steroid administration.
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