Glasdegib

SKU: orb1300702

Description

Glasdegib (PF-04449913) is a potent, orally active Smoothened (Smo) antagonist with an IC50 of 5 nM. This small molecule inhibitor is used in research to study Hedgehog signaling pathway dysregulation in cancers, demonstrating activity in both in vitro assays and in vivo models.

Research Area

Pharmacology & Drug Discovery, Stem Cell & Developmental Biology

Key Properties

• CAS Number: 1095173-27-5
• MW: 374.44
• Purity: 98.72% (May vary between batches)
• Formula: C₂₁H₂₂N₆O
• SMILES: CN1CC[C@H](C[C@@H]1c1nc2ccccc2[nH]1)NC(=O)Nc1ccc(cc1)C#N
• Target: Hedgehog/Smoothened,Smo
• Solubility: 10% DMSO+40% PEG300+5% Tween 80+45% Saline:2 mg/mL (5.34 mM);DMSO:48 mg/mL (128.19 mM);Ethanol:< 1 mg/mL (insoluble or slightly soluble);H2O:< 1 mg/mL (insoluble or slightly soluble)

Bioactivity

• Target IC50:
  Smo:5 nM
• In Vivo:
  In rat and dog, PF-04449913 shows high clearance, and good oral bioavailability.
• In Vitro:
  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.
• Cell Research:
  PF-04449913 is dissolved in DMSO and stored, and then diluted with appropriate medium before use. Normal or BC CML CD34+ cells are plated on confluent mitomycin-C treated SL/M2 cells with vehicle, PF-04449913 (1 μM), Dasatinib (50 nM), or combination treatment. Mouse bone marrow stromal cell lines, M2-10B4 (M2) and SL/SL (SL) are treated with mitomycin-C (1 mg/mL) and plated in a 1:1 mixture at a total concentration of 100,000 cells/mL one day prior to co-culture with 10,000-20,000 CD34+ BC CML or normal progenitors. After 1 week of culture, progenitors are FACS sorted into hematopoietic progenitor assays and colonies are scored at 14 days. To assess survival of normal human hematopoietic stem and progenitor cells, irradiated (20 Gray) OP9 (M2 clone) stromal cells are co-cultured with 50,000 human CD34+ cord blood cells, vehicle or PF-04449913 in AlphaMEM with 20% Hyclone FBS, 1% pen strep glutamine and supplemented with 50 ng/mL SCF, 10 ng/mL thrombopoietin, and 10 ng/mL Flt3 and quantified by weekly FACS analysis.

Storage & Handling

• Storage: Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice/Shipping at ambient temperature.
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

Smo, Smoothened, PF 04449913, PF04449913, PF-04449913, Inhibitor, inhibit, Glasdegib, Hedgehog

Compound Identifiers

PubChem CID

25166913