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Glasdegib (PF-04449913) inhibits sonic hedgehog (Shh) stimulated luciferase expression in mouse embryonic fibroblasts with an IC50 of 6.8 nM. In vitro microsomal assays, PF-04449913 have high clearance in rat and low clearance in dog and human, without inhibiting any of the major cytochrome P450 isoforms.
In vivo, CD34+ cord blood engrafted NSG mice are treated with Glasdegib (PF-04449913), the frequency of human CD45+ cells, progenitors and both myeloid and lymphoid cell fate commitment remained comparable to vehicle treated controls indicating that unlike LSC, normal human HSC cell fate decisions are Hh pathway independent.
| Molecular Weight | 374.44 |
| Formula | C21H22N6O |
| CAS Number | 1095173-27-5 |
| Solubility (25°C) | DMSO: ≥ 65 mg/mL |
| Storage |
Powder -20°C 3 years ; 4°C 2 years In solvent -80°C 6 months ; -20°C 1 month |
[1] Sadarangani A, et al. J Transl Med. GLI2 inhibition abrogates human leukemia stem cell dormancy.
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