796-42-9

AS-8351 is a histone demethylase inhibitor. It has been used in combination with CHIR99021 (Item No. 13122), A 83-01 (Item No. 9001799), BIX01294 (Item No. 13124), SC-1 (Item No. 10009557), Y-27632 (Item No. 10005583), OAC2 (Item No. 14103), SU 16f (Item No. 19555), and JNJ-10198409 (Item No. 10008131) to induce reprogramming of human fetal lung fibroblasts into functional cardiomyocytes.

AS 8351 is used in the conversion of human fibroblasts into functional cardiomyocytes, which provides a promising source for regenerative therapy.

H2La, H2Lb and H2Lc were synthesized using a standard method: equimolar amounts of isonicotinic acid hydrazide (pyridine-4-carbohydrazide) were reacted with the corresponding aldehydes (5-bromo-2-hydroxybenzaldehyde, 2-hydroxy-1-naphthylaldehyde, or 2,4-dihydroxybenzaldehyde) in ethanol by refluxing the compounds for 3 h, followed by cooling to room temperature. Crystals suitable for X-ray crystallographic analysis were obtained by slow evaporation of a dilute ethanol solution of the compound.

in a previous study, in order to identify indispensable factors for human fibroblasts, the authors removed combined compounds one by one and treated cells with the remaining compounds. results showed that the number of beating clusters was significantly reduced by removal of seven compounds including as8351. moreover, these seven compounds inlcuding as8351 were sufficient and necessary to induce cardiac reprogramming efficiently. the authors then investigated the role of the reprogramming compound of as8351 and the results showed that as8351 and its functional analogs could affect epigenetic modifications by competing with α- ketoglutarate for chelating iron/fe(ii) in some epigenetic enzymes, including the jmjc-domain-containing histone demethylases that require α-kg and iron as co-factors. in addition, the authors abrogated each of the 22 genes in the jmjc-kdm family by small hairpin rnas and found that only with kdm5b knockdown, or using a kdm5b inhibitor, pbit could phenocopy as8351 in generating cicms, indicating that it might be a target of as8351 [1].

KDM5

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1) Cao et al. (2016), Conversion of human fibroblasts into functional cardiomyocytes by small molecules; Science, 352 1216