Fig. 1
From: CDK8/19 inhibition plays an important role in pancreatic β-cell induction from human iPSCs
Mutagenicity of the naphthyridine derivative and endocrine cell inducer ALK5 inhibitor II in the Ames test. a Schematic representation of the protocol for iPIC differentiation from hiPSCs. Small-molecule compounds (14 reagents; 11 widely used reagents plus 3 original ones in italic) are highlighted in bold. Act A, activin A; CHIR, CHIR99021; K-CYC, KAAD-cyclopamine; TTNPB, 4-[(E)-2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)-1-propenyl] benzoic acid; ROCKi, TR05991851; PDBu, phorbol 12, 13-dibutyrate; SANT, SANT-1; ALK5iII, ALK5 inhibitor II; LDN, LDN-193189; XAV, XAV939; Y, Y-27632; GSI, RO4929097; PD, PD-166866; R428, bemcentinib; and TR, TR06141363. b Flowchart of mutagenicity evaluation of the 14 compounds used in the iPIC differentiation protocol. Red and blue arrows indicate positive and negative results, respectively. Cpds, compounds. c Positive results (more than twofold increase above the value in the concurrent vehicle control) in the bacterial reverse mutation assay in the absence of rat liver S9 fraction. 9-AA, 9-aminoacridine; ICR, ICR 191. d Summary of the mutagenicity evaluation results for ALK5iII, a non-ALK5 inhibitor structurally related to ALK5iII (TR04411299), and other ALK5 inhibitors (SB525334 and SB431542)