Table 2.
Small molecule-based signalling pathway modulators and cytokines supporting efficient iPSC derivation.
| small molecule | mechanism | function | references |
|---|---|---|---|
| 5-azacytidine (AZA) | DNA methyltransferase inhibitor | promotion of reprogramming c-Myc replacement |
[40] |
| 8-Br-cAMP | human cAMP-dependent protein kinase activator | promotion of reprogramming | [41] |
| A83-01 | TGF-β receptor ALK5/4/7 inhibitor | promotion of reprogramming | [42] |
| AM580 | retinoic acid receptor a agonist | promotion of reprogramming | [43,44] |
| compound B6 | AKT-mediated inhibitor of GSK3-b | promotion of reprogramming | [45] |
| compound B4 | ALK4 inhibitor | promotion of reprogramming | [45] |
| compound B8 | IP3K inhibitor | promotion of reprogramming | [45] |
| compound B10 | P38 kinase inhibitor | promotion of reprogramming | [45] |
| DAPT | γ-secretase inhibitor | promotion of reprogramming | [46] |
| DZNep | histone methyltransferase EZH2 inhibitor | promotion of reprogramming | [47] |
| DNP | oxidative phosphorylation uncoupler | promotion of reprogramming | [42] |
| EPZ004777 | DOT1 L inhibitor | promotion of reprogramming | [48] |
| fructose 2,6-bisphosphate | phosphofructokinase 1 activator | promotion of reprogramming | [42] |
| LiCl | GSK-3b inhibitor, LSD1 inhibitor | promotion of reprogramming | [49] |
| N-oxaloylglycine | prolyl-4-hydroxylase inhibitor | promotion of reprogramming | [42] |
| NaB (sodium butyrate) | HDAC inhibitor | promotion of reprogramming | [50] |
| nicotinamide | inhibition of the H3K79 histone methyltransferase DOT1 L | promotion of reprogramming | [51,52] |
| PD0325901 | potent MEK1 and MEK2 inhibitor | promotion of reprogramming inhibits growth of non-iPS cell colonies |
[53] |
| PS48 | PDK1 activator | promotion of reprogramming | [42] |
| prostaglandin | cAMP agonists | promotion of reprogramming | [47] |
| quercetin | hypoxia-inducible factor pathway activator | promotion of reprogramming | [42] |
| rapamycin | mTOR inhibitor activating autophagy |
promotion of reprogramming | [54] |
| RG108 | DNA methyltransferase inhibitor | promotion of reprogramming Sox2 (with BIX) or Oct3/4 substitute |
[55] |
| RSC133 | DMNT inhibitor | promotion of reprogramming | [56] |
| rolipram | cAMP agonists | promotion of reprogramming | [47] |
| SAHA | HDAC inhibitor | promotion of reprogramming | [40] |
| SB431542 | TGF-β receptor ALK5/4/7 inhibitor | promotion of reprogramming | [57] |
| SGC0496 | DOT1 L inhibitor | promotion of reprogramming | [58] |
| SMER28 | autophagy modulator | promotion of reprogramming | [59] |
| Tranylcypromine (Parnate) | lysine-specific demethylase 1 inhibitor | promotion of reprogramming | [57] |
| TSA | HDAC inhibitor | promotion of reprogramming | [40] |
| TTNPB | retinoic acid receptor ligand | promotion of reprogramming | [47] |
| VPA | HDAC inhibitor | promotion of reprogramming | [60,61] |
| Y-27632 | ROCK inhibitor | promotion of reprogramming | [62] |
| 2-Me-5HT | 5-HT3 agonist | Oct3/4 substitute | [47] |
| BIX-01294 | G9a histone lysine methyltransferase inhibitor | Oct3/4 substitute | [53,63] |
| D4476 | mouse CK1 inhibitor | Oct3/4 substitute | [47] |
| Forskolin (FSK) | PKA activator, mouse cAMP agonist | Oct3/4 substitute | [47] |
| O4I1 (modifications 1-11) | unknown | Oct3/4 substitute | [64] |
| O4I2 (modifications 1-21) | unknown | Oct3/4 substitute | [65] |
| OAC1 | activates Oct3/4 and Nanog promoters | Oct3/4 substitute | [45,66] |
| OAC2 | activates Oct3/4 and Nanog reporters | Oct3/4 substitute | [45] |
| BayK | L-channel calcium agonist | Sox2 substitute | [55] |
| CHIR99021 | GSK-3 inhibitor Wnt pathway activator |
Sox2 substitute | [60] |
| Dasatinib | Src family tyrosine kinase inhibitor | Sox2 substitute | [67] |
| iPY | Src family tyrosine kinase inhibitor | Sox2 substitute | [67] |
| LY-364947 | TGF-b inhibitor | Sox2 substitute | [67] |
| PP1 | Src family tyrosine kinase inhibitor | Sox2 substitute | [67] |
| Repsox (E-616452) | TGFβ receptor I kinase inhibitor | Sox2 substitute | [68] |
| Kenpaullone | GSK-3 and CDK1/cyclin B inhibitor | Klf4 substitute | [69] |
| AMI5 | protein arginine methyltransferase (PRMT) inhibitor | Sox2, Klf4 substitute (with A-83-01) | [70] |
| Hh-Ag 1.5 | Smo agonist activating MAPK and SHH pathways | Sox2 and Nestin induction | [59] |
| Oxysterol | sonic hedgehog signalling activator | Sox2, Klf4, and C-Myc substitute | [71] |
| Purmorphamine | hedgehog activator | Sox2, Klf4, and C-Myc substitute differentiation inducer to neural stem cells |
[71,72] |
| Shh | sonic hedgehog signalling | Sox2, Klf4 and C-Myc substitute | [71] |
| (±) BayK 8644 | L-type calcium channel agonist | increase in spontaneous beating frequency promotion of reprogramming maintenance of pluripotency |
[73] |
| JNJ-10198409 | PDGFR-a and PDGFR-b inhibitor | increase in spontaneous beating frequency differentiation inducer to cardiomyocytes |
[74] |
| SU16F | PDGFR inhibitor | increase in spontaneous beating frequency promotion of reprogramming differentiation inducer to cardiomyocytes |
[74] |
| ATRA | retinoic acid receptor agonist | differentiation inducer to extra-embryonic lineage | [75,76] |
| AS8351 | epigenetic modifications modulation of a specific JmjC-KDM |
differentiation inducer to cardiomyocytes | [77] |
| JAK inhibitor 1 (JI1) | JAK–STAT pathway inhibitor | differentiation inducer to cardiomyocytes | [78] |
| SC1 (pluripotin) | dual inhibitor of extracellular signal-regulated kinase 1 and RasGAP/inhibitor of the ERK1 and Ras-GAP signalling pathways | differentiation inducer to cardiomyocytes | [73,74] |
| SU5402 | FGFR, VEGFR and PDGFR inhibitor | differentiation inducer to cardiovascular progenitor cells | [79] |
| Poly(I:C) | toll-like receptor 3 agonist | differentiation inducer to endothelial cells | [80] |
| Go 6983 | broad spectrum protein kinase C inhibitor | differentiation inducer to neurons | [62] |
| I-BET151 | BET bromodomain inhibitor | differentiation inducer to neurons | [81] |
| ISX9 | neurogenic agent | differentiation inducer to neurons | [81] |
| LDN193189 | BMP receptor ALK2 and ALK3 antagonists | differentiation inducer to neurons | [59,82] |
| Pifithrin-α (PFT-α) | p53 inhibitor | differentiation inducer to neurons | [83] |
| SAG | hedgehog activator smoothened agonist | differentiation inducer to neurons | [46] |
| SP600125 | JNK inhibitor | differentiation inducer to neurons | [62] |
| Thiazovivin (Tzv) | selective ROCK inhibitor | differentiation inducer to neurons | [46] |