O4I3 is a potent and selective inhibitor of the KDM5A (JARID1A) isoform of H3K4 demethylase (KDM5A IC50 = 0.15 nM vs. KDM5B/C/D IC50 = 125.2/9.76/4. 7 nM, KDM4 IC50 = 249 nM, and LSD1 IC50 >100 μM), and O4I3 can induce OCT4 expression and enhance OSKM-induced pluripotent stem cells (iSCs) by preventing KDM5A from interfering with H3K4Me3 enrichment at the OCT4 promoter, thus effectively inducing OCT4 expression and improving OSKM-induced reprogramming efficiency of human primary fibroblast pluripotent stem cells (iPSC) (50 nM). In addition, O4I3 promoted hPSC homeostasis and inhibited cell differentiation, and increased hPSC survival by 4-fold at a low concentration of 10 nM compared with Rock inhibitor Y-27632 at 10 μM.
| Molecular Weight | 222.29 |
| Formula | C15H14N2 |
| CAS Number | 88965-00-8 |
| Form | Solid |
| Solubility (25°C) | DMSO 2 mg/mL |
| Storage | 4°C |
| Species | Mouse | Rat | Rabbit | Guinea pig | Hamster | Dog |
| Weight (kg) | 0.02 | 0.15 | 1.8 | 0.4 | 0.08 | 10 |
| Body Surface Area (m2) | 0.007 | 0.025 | 0.15 | 0.05 | 0.02 | 0.5 |
| Km factor | 3 | 6 | 12 | 8 | 5 | 20 |
| Animal A (mg/kg) = Animal B (mg/kg) multiplied by | Animal B Km |
| Animal A Km |
For example, to modify the dose of Compound A used for a mouse (20 mg/kg) to a dose based on the BSA for a rat, multiply 20 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for Compound A of 10 mg/kg.
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