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].

Signaling Pathways >> Stem Cell/Wnt >> GSK-3

Signaling Pathways >> Membrane Transporter/Ion Channel >> CFTR

Research Areas >> Cancer

Research Areas >> Inflammation/Immunology

Signaling Pathways >> Cell Cycle/DNA Damage >> CDK

Signaling Pathways >> MAPK/ERK Pathway >> ERK

Signaling Pathways >> MAPK/ERK Pathway >> JNK

Signaling Pathways >> PI3K/Akt/mTOR >> GSK-3

Signaling Pathways >> Stem Cell/Wnt >> ERK

CDK1/cyclinB:0.15 μM (IC50)

CDK2/cyclinA:0.12 μM (IC50)

CDK2/cyclinE:0.4 μM (IC50)

CDK5/p35:0.16 μM (IC50)

GSK-3β:0.5 μM (IC50)

GSK-3α:1.5 μM (IC50)

JNK:3-10 μM (IC50)

ERK1:18 μM (IC50)

ERK2:22 μM (IC50)

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].

[1]. Yvette Mettey, et al. Aloisines, a new family of CDK/GSK-3 inhibitors. SAR study, crystal structure in complex with CDK2, enzyme selectivity, and cellular effects. J Med Chem. 2003 Jan 16;46(2):222-36.

[2]. Sabrina Noel, et al. Discovery of pyrrolo[2,3-b]pyrazines derivatives as submicromolar affinity activators of wild type, G551D, and F508del cystic fibrosis transmembrane conductance regulator chloride channels. J Pharmacol Exp Ther. 2006 Oct;319(1):349-59.