Reprogramming with Small Molecules instead of Exogenous Transcription Factors

Table 2

Small molecule compounds that might replace Yamanaka factors.

Replacement; for TF	Name; concentration	Concentration	Host cell species	Function or target	Reference
Oct4, Nanog	SAHA-PIP delta	100 nM	Mouse	Histone deacetylase inhibitor	Pandian et al. (2014) [65]
Sox2 (with BIX) or Oct4	RG108	0.04–500 μM	Mouse	DMNT inhibitor	Shi et al. (2008) [32, 33, 72]
Oct4	BIX	0.5–2 μM	Mouse	G9a HMTase inhibitor	Shi et al. (2008) [32, 33, 72]
Sox2	CHIR	3–10 μM	Mouse, human	GSK-3β inhibitor that activates Wnt signalling pathway	Li et al. (2011) [73]
Klf4	Kenpaullone	5 μM	Mouse	GSK-3/CDKs inhibitor	Lyssiotis et al. (2009) [42]
Sox2	616452 (E-616452, Repsox)	1 μM	Mouse, human	TGF-β inhibitor (ALK inhibitor II)	Ichida et al. (2009) [63]
Sox2	LY-364947	1 μM	Mouse	TGF-β inhibitor	Staerk et al. (2011) [74]
Sox2, Klf4 (with A-83-01)	AMI-5	5 μM	Mouse	Protein arginine methyltransferase inhibitor	Yuan et al. (2011) [64]
Sox2	Dasatinib	0.5 μM	Mouse	Src family tyrosine kinase inhibitor	Staerk et al. (2011) [74]
Sox2	iPYrazine (iPY)	10 μM	Mouse	Src family tyrosine kinase inhibitor	Staerk et al. (2011) [74]
Sox2	PP1	10 μM	Mouse	Src family tyrosine kinase inhibitor	Staerk et al. (2011) [74]
Oct 4 with FSK and 2-Me-5HT	D4476	5 μM	Mouse	CK1 inhibitor	Hou et al. (2013) [27]
Sox2	BayK	2 μM	Mouse	An L-channel calcium agonist	Shi et al. (2008) [32, 33, 72]
Oct4, when used with 2-Me-5HT, and D4476	FSK	10–50 μM	Mouse	cAMP agonist	Hou et al. (2013) [27]
Oct4 with FSK and D4476	2-Me-5HT	5 μM	Mouse	5-HT3 agonist	Hou et al. (2013) [27]
Sox2, Klf4, and C-Myc	Oxysterol	0.5–1 μM	Mouse	Sonic hedgehog signaling	Moon et al. (2011) [75]
Sox2, Klf4, and C-Myc	Purmorphamine	0.5–1 μM	Mouse	Sonic hedgehog signaling	Moon et al. (2011) [75]
Sox2, Klf4, and C-Myc	Shh	500 ng/mL	Mouse	Sonic hedgehog signaling	Moon et al. (2011) [75]

Note: small molecules can substitute for certain TFs and/or improve reprogramming efficiency by epigenetic modifications or signaling pathway regulation. BayK, Bay K8644; BIX, BIX-01294; CHIR, CHIR99021; CK1, casein kinase 1; DNMT, DNA methyltransferase; DNP, 2,4-dinitrophenol; DZNep, 3-deazaneplanocin; FSK, forskolin; HDAC, histone deacetylase; G9a HMTase, G9a histone ethyltransferase; IP3K, inositol triphosphate 3-kinase; PDK1, phosphoinositide dependent kinase 1; SAHA, suberoylanilide hydroxamic acid; TF, transcription factor; TSA, trichostatin A; VPA, valproic acid; 2-Me-5HT, 2-methyl-5-hydroxytryptamine; 5-aza-CR, AZA, 5-azacytidine; 8-Br-cAMP, 8-bromoadenosine cyclic monophosphate.