Aloisine A

Aloisine A (RP107) is a a potent cyclin-dependent kinase (CDK) inhibitor with IC₅₀s of 0.15 μM, 0.12 μM, 0.4 μM, 0.16 μM for CDK1/cyclin B, CDK2/cyclin A, CDK2/cyclin E, CDK5/p35, respectively. Aloisine A ininhibits GSK-3α (IC₅₀=0.5 µM) and GSK-3β (IC₅₀=1.5 µM). Aloisine A stimulates wild-type CFTR and mutated CFTR, with submicromolar affinity by a cAMP-independent mechanism. Aloisine A has the potential for CFTR-related diseases, including cystic fibrosis research^[1][2]. In Vitro: Aloisine A ininhibits erk1 (IC₅₀=18 µM), erk2 (IC₅₀=22 µM), c-Jun N-terminal kinase (JNK; IC₅₀~3-10 µM). Aloisine A has no effect on protein kinase C α, β1, β2, γ, δ, ε, η, ξ (all IC₅₀>100 µM)^[1].
Aloisine A (0.1, 1, 10, 100 µM) completely blocks the proliferation of dividing NT2 cells (IC₅₀=7 μM) and differentiated postmitotic neurons (hNT; IC₅₀=10.5 μM), and very few cells actually die^[1].
Aloisine A acts as a submicromolar activator of wild-type (WT)-CFTR [human airway epithelial Calu-3 and WT-CFTR-Chinese hamster ovary (CHO) cells], G551D-CFTR (G551D-CFTR-CHO cells), and F508del-CFTR (in temperature-corrected human airway epithelial F508del/F508del CF15 cells)^[2].