Table 2.
Small molecule activators/inhibitors known to modulate the differentiation of hESCs
| Drug | Target | Pathway | Differentiated Cell Fate | Reference |
|---|---|---|---|---|
| 1-EBIO | Ca2+ Activated K+ Channels | Cardiac and cardiac pacemaker-like cells | (Müller et al., 2011) | |
| 1m | GSK3β | WNT | Primitive streak, mesoderm, definitive endoderm | (Bone et al., 2011) |
| 5-Azacytidine/5-aza-2'-deoxycytidine | DNMT's | Cardiomyocyte | (Wang et al., 2010; Xu et al., 2002; Yoon et al., 2006) | |
| ALK5-I/II Inhibitor + DAPT | ALK5 +γ-secretase | TGFβ+ NOTCH | Pancreatic endocrine cells | (Rezania et al., 2011) |
| ATRA | RARs/RXRs | Mainly neurogenesis | (Desbordes et al., 2008) | |
| BIO + SB431542 | GSK3β+ ALK4,5 & 7 | WNT + TGFβ | Neural crest | (Menendez et al., 2011) |
| BMS-189453 + NOGGIN | RARs/RXRs | Cardiomyocytes | (Zhang et al., 2011) | |
| CHIR99021 + DORSOMORPHIN + RA + SB431542 | GSK3β+ ALK2, 3 and 6+ ALK4,5 & 7 | WNT + TGFβ | hiPSCs into definitive endoderm then pancreatic cells | (Kunisada et al., 2011) |
| CHIR99021 + SB431542 + Compound E | GSK3β+ ALK4,5 & 7 +γ-secretase | WNT + TGFβ+ NOTCH | Cardiomyocytes | (Kattman et al., 2011) |
| Chlorate | Downregulation of Sulfonation | WNT, TGFβ, and FGF/ERK | Mature neurons | (Sasaki et al., 2010) |
| Cobalt chloride | HIF-1α stabilization | Cardiomyocyte differentiation to functionally mature cardiomyocytes | (Ng et al., 2011) | |
| Corticosteroids | Trophoblast and mesodermal | (Barbaric et al., 2010) | ||
| CSA | Calcineurin | NFAT | Cardiomyocyte differentiation from ESC-derived mesodermal cells in visceral endodermal stromal cell co-culture | (Mummery et al., 2003) |
| Decreased hypertrophy of ESC-derived cardiomyocytes | (Lim et al., 2000) | |||
| Cyclopamine | SMO | Hh | Astrocytes | (Lee et al., 2006) |
| Cymarin | RARs/RXRs | Mesodermal/endodermal | (Desbordes et al., 2008) | |
| Dorsomorphin | ALK2, 3 and 6 | TGFβ | Neurogenesis | (Kim et al., 2010; Wada et al., 2009; Zhou et al., 2010) |
| Dorsomorphin + SB431542 | ALK2, 3 and 6 + ALK4,5 & 7 | TGFβ | Pancreatic Cells Neurogenesis | (Nostro et al., 2011) |
| (Kim et al., 2010; Morizane et al., 2011) | ||||
| IDE1 and 2 | TGFβ | Definitive endoderm | (Borowiak et al., 2009) | |
| ILV + KAAD-Cyclopamine | PKCs + SMO | Hh | Pancreatic Progenitors | (Chen et al., 2009; D’Amour et al., 2006; Kroon et al., 2008; Thatava et al., 2011). |
| IWP-4, IWR-1 | WNT | Cardiomyocytes | (Hudson et al., 2011) | |
| IWR-1 | WNT | Cardiomyocytes | (Ren et al., 2011) | |
| IWR-1, IWP-3 | WNT | Cardiomyocytes | (Willems et al., 2011) | |
| LY294002 | PI3K | PI3K/AKT/mTOR | Endodermal | (Touboul et al., 2010) |
| NaB | Histone Proteins | Hepatocytes differentiation Endodermal and trophectodermal | (Hay et al., 2008) (Maimets et al., 2008) | |
| Nutlin | TP53 | Primitive endoderm and trophectoderm differentiation | (Maimets et al., 2008) | |
| PD98059 | MAP2K1/MEK1 | MEK/ERK | Haematopoietic and functional endothelial and smooth muscle cells | (Park et al., 2010) |
| Purmorphamine | SMO | Hh | Ventral spinal progenitors and motor neurons | (Li et al., 2008) |
| RA | Functional Insulin Producing Cells | (Jiang et al., 2007) | ||
| Rapamycin | mTOR | PI3K/AKT/mTOR | Mesodermal and endodermal | (Zhou et al., 2009) |
| Osteogenesis | (Lee et al., 2010) | |||
| Red Ginseng | Cardiac-progenitor like cells from hESC-derived EBs. | (Kim et al., 2011) | ||
| Rosiglitazone | PPARγ | Adipocytic Differentiation | (Xiong et al., 2005) | |
| Sarmentogenin | Mesodermal/Endodermal | (Desbordes et al., 2008) | ||
| SB203580 | p38 MAPK | MAPK | Cardiomyogenesis | (Gaur et al., 2010; Kempf et al., 2011) |
| SB431542 | ALK4,5 & 7 | TGFβ | Primitive NPCs | (Li et al., 2011) |
| Myocyte progenitors | (Mahmood et al., 2010) | |||
| hESC-derived hemogenic epithelial cells into HPCs | (Wang et al., 2011) | |||
| Cardiomyocytes | (Graichen et al., 2008; Xu et al., 2008), | |||
| Endothelial cells | (James et al., 2010). | |||
| hESC-derived endoderm cells into hepatic progenitors | (Touboul et al., 2010) | |||
| SB431542 + CKI-7 | ALK4,5 & 7 + Casein Kinase | TGFβ+ LEFTYA | Retinal | (Osakada et al., 2009) |
| SB431542 + NOGGIN | ALK4,5 & 7 + BMP | TGFβ | Neurogenesis | (Chambers et al., 2009) |
| Anterior Foregut Endoderm | (Green et al., 2011) | |||
| Endocrine differentiation from hESC-derived pancreatic progenitors | (Nostro et al., 2011) | |||
| SB431542 + Purmorphamine | ALK4,5 & 7 + SHH | TGFβ+ SHH | Motor Neuron Precursors | (Patani et al., 2009) |
| SP60125 | JNK/AP-1 | Non-canonical WNT | Haematopoiesis | (Rai et al., 2011) |
| Stauroprimide | Primes for multilineage differentiation | (Zhu et al., 2009) | ||
| Synthetic RA Analogues | RARs/RXRs | Mainly Neurogenesis | (Christie et al., 2008) |