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Purity: ≥98%
Glasdegib (formerly known as PF-04449913; PF4449913; PF04449913; PF-4449913; Daurismo) is a novel, potent, and orally bioavailable small-molecule inhibitor of Smoothened (Smo) in the Hedgehog (Hh) signaling pathway with potential antitumor activity. It is a drug that was authorized in 2018 to treat acute myeloid leukemia that has just been discovered. Smoothened (Smo) is inhibited by Glasdegib at a 5 nM IC50. Cellular development, differentiation, and repair are all significantly impacted by the Hh signaling pathway. Many forms of cancer have been shown to exhibit constitutive activation of the Hh pathway signaling. In a Ptch1+/-p53+/- allograft model, Glasdegib dramatically inhibits the growth of medulloblastoma at doses that also reduce the expression of the murine Shh target gene. When PF-04449913 is used in stromal co-culture experiments, FACS analysis shows a significant decrease in BC LSC relative to normal progenitors.
| Targets |
Smo ( IC50 = 4 nM )
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| ln Vitro |
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| Enzyme Assay |
Glasdegib, a novel potent small-molecule inhibitor with an IC50 of 5 nM, is an oral bioavailable inhibitor of Smoothened (Smo) in the Hedgehog (Hh) signaling pathway. It was previously known as PF-04449913. In cells, the Hh signaling pathway is essential for growth, differentiation, and repair. In many different kinds of cancer, constitutive activation of the Hh pathway signaling has been reported. In an allograft model with Ptch1+/-p53+/-, Glasdegib dramatically inhibits the growth of medulloblastoma at doses that also reduce the expression of the murine Shh target gene. When compared to normal progenitors, FACS analysis shows a significant reduction in BC LSC by PF-04449913 in stromal co-culture experiments.
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| Cell Assay |
BMS-354825 (50 nM), Glasdegib (PF-04449913) (1 μM), or a combination of these treatments are used to treat CD34+cells in BC CML or normal cells. The M2-10B4 (M2) and SL/SL (SL) mouse bone marrow stromal cell lines are plated 1:1 mixture at a final concentration of 100,000 cells/mL one day before being co-cultured with 10,000–20,000 CD34+BC CML or normal progenitors. At 14 days, progenitors are scored and FACS sorted into hematopoietic progenitor assays following a week of culture. Normal human hematopoietic stem and progenitor cells are evaluated for survival using the following methods: irradiated (20 Gray) OP9 (M2 clone) stromal cells are co-cultured with 50,000 human CD34+cord blood cells, vehicle, or Glasdegib (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. The results are recorded using weekly FACS analysis[1].
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| References |
| Molecular Formula |
C21H22N6O
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| Molecular Weight |
374.44
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| Exact Mass |
374.19
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| Elemental Analysis |
C, 67.36; H, 5.92; N, 22.44; O, 4.27
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| CAS # |
1095173-27-5
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| Related CAS # |
1095173-27-5; 2030410-25-2; 1095173-64-0 (HCl); 1352568-48-9 (2HCl)
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| Appearance |
White solid powder
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| SMILES |
CN1CC[C@H](C[C@@H]1C2=NC3=CC=CC=C3N2)NC(=O)NC4=CC=C(C=C4)C#N
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| InChi Key |
SFNSLLSYNZWZQG-VQIMIIECSA-N
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| InChi Code |
InChI=1S/C21H22N6O/c1-27-11-10-16(24-21(28)23-15-8-6-14(13-22)7-9-15)12-19(27)20-25-17-4-2-3-5-18(17)26-20/h2-9,16,19H,10-12H2,1H3,(H,25,26)(H2,23,24,28)/t16-,19-/m1/s1
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| Chemical Name |
1-[(2R,4R)-2-(1H-benzimidazol-2-yl)-1-methylpiperidin-4-yl]-3-(4-cyanophenyl)urea
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| Synonyms |
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (5.55 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.08 mg/mL (5.55 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.08 mg/mL (5.55 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.6707 mL | 13.3533 mL | 26.7065 mL | |
| 5 mM | 0.5341 mL | 2.6707 mL | 5.3413 mL | |
| 10 mM | 0.2671 mL | 1.3353 mL | 2.6707 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT03466450 | Active Recruiting |
Drug: PF-04449913 Drug: Temozolomide Oral Capsule |
Glioblastoma | Grupo Español de Investigación en Neurooncología |
March 15, 2018 | Phase 1 Phase 2 |
| NCT03415867 | Completed | Drug: Glasdegib | Sclerodermoid Chronic Graft- Versus-Host Disease (Disorder) |
Grupo Espanol de trasplantes hematopoyeticos y terapia celular |
January 9, 2018 | Phase 1 Phase 2 |
| NCT04231851 | Recruiting | Drug: Glasdegib Drug: CPX-351 |
Acute Myelogenous Leukemia (AML) Due to Therapy |
University of California, Irvine | February 19, 2020 | Phase 2 |
| NCT04168502 | Recruiting | Drug: Glasdegib | Acute Myeloid Leukemia | Gruppo Italiano Malattie EMatologiche dell'Adulto |
September 24, 2020 | Phase 3 |
| NCT02430545 | Recruiting | Drug: Glasdegib Drug: Rifampin |
Healthy Volunteers | Pfizer | May 2015 | Phase 1/td> |
 Selective shh inhibition reduces lsc burden in stromal co-cultures.J Transl Med.2015 Mar 21;13:98. |
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Shh inhibition induces cycling of dormant leukemic progenitors.J Transl Med.2015 Mar 21;13:98. |
PF-04449913 induced cell cycle activation enhances TKI sensitivity.J Transl Med.2015 Mar 21;13:98. |
GLI2 induces cell cycle arrest in leukemic progenitors.J Transl Med.2015 Mar 21;13:98. |
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SHH pathway deregulation in chronic myeloid leukemia progression.J Transl Med.2015 Mar 21;13:98. |
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