Stem Cells International

Review Article

Small Molecule Epigenetic Modulators in Pure Chemical Cell Fate Conversion

Table 1

Small molecules involved in pure small molecule-induced reprogramming or transdifferentiation.
Name of the compoundsMain mechanism of actionApplication in reprogramming or transdifferentiationReferences
Signaling pathways
TGF-β signaling pathways
A83-01TGF-beta RI (ALK4/5/7) inhibitorCiNSCs, CiNs, CiBCs, CiPSCs, CiBLPCs, CiCMs, CiEPCs[16, 27, 28, 30–34, 46, 55–57, 62, 64]
RepSox (E-616452)TGF-beta RI (ALK5) inhibitorCiPSCs, CiNs, CiCMs, CiPCs, CiSMCs, CiCCs[14, 17–19, 21, 22, 40, 41, 45, 52, 61, 69, 71, 79]
SB431542Inhibitor of TGF-βRI, ALK4, and ALK7CiEPCs, CiNs, CiCMs, CiLCs[35, 43, 55–57, 59, 75]
IDE 1Activator of TGF-β signaling pathwayCiBCs[64]
DMH1Inhibitor of ALK2CiNs[41]
BMP signaling pathways
DorsomorphinBMP receptor inhibitorCiNs[42]
LDN193189BMP type I receptor (ALK2/3) inhibitorCiNSCs, CiNs[30, 42, 43]
Wnt signaling pathway
CHIR99021GSK3 inhibitorCiPSCs, EPSs, CiNSCs, CiBLPCs, CiNs, CiCMs, CiPCs, CiSMCs[15, 17–19, 21, 22, 25–28, 30–34, 39–43, 45, 47, 52, 59, 61, 62, 69, 78, 79]
LiClGSK3 inhibitorCiBCs[64]
XAV939Wnt/beta-catenin inhibitorEPSs[26]
IWR1Wnt/beta-catenin inhibitorCiPCs[52]
CHIR-98014GSK3 inhibitor
TWS119GSK3 inhibitor
TideglusibGSK3 inhibitor
BIOGSK3 inhibitor
AZD2858GSK3 inhibitor
TDZD-8GSK3 inhibitor
IndirubinGSK3 inhibitor
PNU-74654Wnt/beta-catenin inhibitor
IWP-2Wnt/beta-catenin inhibitor
MAPK/ERK signaling pathway
PD0325901Inhibitor of MEK1/2CiPSCs, CiCMs, CiNs, EPSs[22, 26, 42, 61]
SC1ERK1 and RasGAP inhibitorCiCMs[62]
Rho signaling pathway
ThiazovivinROCK inhibitorCiNs[43]
Y-27632ROCK inhibitorCiNs, CiBLPCs, CiCMs[31–33, 40, 42, 46, 47, 58, 62, 78]
Notch signaling pathway
DAPTGamma-secretase inhibitorCiNs, CiBCs[42, 43, 64]
SHH signaling pathway
Cyclopamine-KAADHedgehog/smoothened inhibitorCiBCs[64]
Hh-Ag 1.5Smoothened agonistCiNSCs[30]
PurmorphamineSmoothened agonistCiNs[42, 43, 46]
Other signaling pathways
A-419259An inhibitor of Src family kinases (SFK)EPS[26]
dbcAMPActivates cAMP-dependent protein kinases[78]
ForskolinAdenylyl cyclase activatorCiPSCs, CiNs, CiPCs, CiSMCs, CiLCs[18, 19, 22, 39–42, 45–47, 52, 59, 61, 69, 75, 78, 79]
Gö6983Inhibitor of protein kinase C (PKC)CiNs[40]
Indolactam VActivator of protein kinase C (PKC)CiBCs[64]
JNJ10198409PDGFR-a and PDGFR-b inhibitor, PDGFR tyrosine kinase inhibitor IVCiCMs[62]
SB203580P38 MAPK inhibitorEPSs, CiBCs[26, 64]
SP600125JNK inhibitorCiNs[40, 41]
SU16FPDGFR-b inhibitorCiCMs[62]
CelecoxibCOX inhibitorCiCCs[71]
Epigenetic modifications
DNA methylation inhibitor
5-Aza-dCDNMT inhibitorCiPSCs[20]
BrdU (bromodeoxyuridine)Analog of thymidineCiPSCs[19, 22]
DZNepSAH hydrolase inhibitorCiPSCs[18, 21, 22]
RG108DNA methyltransferase inhibitorCiNSCs, CiEPCs, CiNs[27, 28, 30, 35, 42]
AMI-5Protein methyltransferase inhibitorCiPSCs[16]
PF-6405761BET inhibitor
Histone deacetylation inhibitor
NaBHDAC inhibitorCiNs, CiCMs[47, 60]
VPAHDAC inhibitorCiPSCs, CiNSCs, CiNs, CiCMs, CiPCs, CiSMCs, CiCCs[13, 17, 18, 21, 22, 27, 28, 40, 41, 43, 45, 47, 52, 61, 69, 71, 79]
I-BET-762BET inhibitor
Histone methylation modulator
AS8351Inhibitor of histone demethylaseCiCMs[62]
Bix01294Histone methyltransferase inhibitorCiCMs, CiEPCs, CiNSCs[27, 28, 35, 62]
BRD 7552Increases acetylation of histone H3 and trimethylation of H3K4 and H3K9CiBCs[64]
EPZ5676DOT1 inhibitorCiPSCs[22]
EPZ004777DOT1L inhibitorCiPSCs[20, 22]
SGC0946DOT1L inhibitorCiPSCs[20, 22]
CPI-0610BET inhibitor
GS-5829BET inhibitor
Histone acetylation modulator
I-BET151Inhibitor of epigenetic readerCiNs[39, 45, 78]
INCB057643BET inhibitor
Metabolic processes
AM580RAR agonistCiPSCs[20–22]
BexaroteneRAR agonistCiAs[68]
Ch55RAR agonistCiPSCs[21]
Retinoic acidRAR ligandCiNSCs, CiNs[30, 46]
TTNPBRAR ligandCiPSCs, CiNs, CiSMCs, CiCCs[18, 43, 47, 61, 69, 71]
Bay-K-8644Ca2+ channel activatorCiEPCs[35]
ISX9Neurogenesis inducerCiNs[39, 42, 78]
LPAA ligand activator for EDG-2, EDG-4, and EDG-7CiBLPCs[33]
Minocycline hydrochlorideBind to the bacterial 30S ribosomal subunit and inhibiting protein synthesisEPSs[25]
OAC2Activator of octamer-binding transcription factor 4 (Oct4)CiCMs[62]
Parnate (Tranylcypromine)Monoamine oxidase inhibitor, LSD1 inhibitorCiPSCs, CiNSCs, CiCMs, CiSMCs[15, 17, 18, 21, 30, 59, 61, 69, 79]
P7C3Targets NAMPT enzymeCiNs[42]
RolipramPDE4 inhibitor[79]
SMER28Autophagy modulatorCiNSCs[30]
(S)-(+)-Dimethindene maleateAntagonist of muscarinic M2 and histamine H1 receptorsEPSs[25]
Vitamin CA strong antioxidantCiPSCs, CiNSCs, CiBCs[22, 27, 28, 64]
CiAs: chemical-induced adipocytes; CiBCs: chemical-induced beta cells; CiBLPCs: chemical-induced bipotent liver progenitor cells; CiCCs: chemical-induced cartilaginous cells; CiCMs: chemical-induced cardiomyocytes; CiECs: chemical-induced epithelial colonies; CiEPCs: chemical-induced endodermal progenitor cells; CiLCs: chemical-induced Leydig cells; CiNs: chemical-induced neurons; CiNPCs: chemical-induced neuroprogenitor cells; CiNSCs: chemical-induced neural stem cells; CiPCs: chemical-induced photoreceptor cells; CiPSCs: chemical-induced pluripotent stem cells; CiSMCs: chemical-induced skeletal muscle cells; EPSs: extended pluripotent stem cells.