product name Glasdegib (PF-04449913)
Description: Glasdegib, also known as PF-04449913, is a potent, and orally bioavailable small-molecule inhibitor of Smoothened (Smo) with IC50 of 5 NM. Glasdegibis appears to inhibit Hh pathway signaling. The Hh signaling pathway plays an important role in cellular growth, differentiation and repair. Constitutive activation of Hh pathway signaling has been observed in various types of malignancies.
References: ACS Med Chem Lett. 2011 Dec 21;3(2):106-11.
374.44
Formula
C21H22N6O
CAS No.
1095173-27-5
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: 47 mg/mL (125.5 mM)
Water: <1 mg/mL
Ethanol: <1 mg/mL
Solubility (In vivo)
Synonyms
other peoduct :References PubMed ID：:http://www.ncbi.nlm.nih.gov/pubmed/19426212
| In Vitro |
In vitro activity: 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. Kinase Assay: Cell Assay: In the Hedgehog (Hh) signaling pathway, the combination of Hh ligands and their receptor Patched leads to the activation of smoothened and subsequently activation of three transcription factors Gli1, Gli2 and Gli3. It then leads to the proliferation of cells. As an antagonist of smoothened, PF-04449913 is developed for treatment of cancer. |
|---|---|
| In Vivo | In rat and dog, PF-04449913 shows high clearance, and good oral bioavailability |
| Animal model | Rat, dog |
| Formulation & Dosage | Dissolved in 10% EtOH/20% PEG400/70% PBS (i.v.); 0.5% methylcellulose in water (p.o.); 1 mg/kg (Rat); 0.5 mg/kg (dog i.v.); 3 mg/kg (dog p.o.); i.v. or p.o. administration |
| References | ACS Med Chem Lett. 2011 Dec 21;3(2):106-11. |
