[CAS NO. 1095173-27-5] Glasdegib
PRODUCTS SPECIFICATIONS [1095173-27-5]
DESCRIPTION [1095173-27-5]
Overview
| MDL | MFCD25976839 |
|---|---|
| Molecular Weight | 374.44 |
| Molecular Formula | C21H22N6O |
| SMILES | O=C(NC1=CC=C(C#N)C=C1)N[C@H]2C[C@H](C3=NC4=CC=CC=C4N3)N(C)CC2 |
2 Publications Citing Use of MCE
Summary
IC50 & Target
IC50: 4 nM (Smo) [1]
In Vitro
Glasdegib (PF-04449913) inhibits sonic hedgehog (Shh) stimulated luciferase expression in mouse embryonic fibroblasts with an IC 50 of 6.8 nM; and significantly reduces medulloblastoma growth in a Ptch1 +/- p53 +/- allograft model at doses that decreased murine Shh target gene expression. In stromal co-culture experiments, FACS analysis demonstrates a significant reduction in BC LSC by Glasdegib (PF-04449913) when compared with normal progenitors. Importantly, human BC LSC engrafted RAG2 -/- γ C -/- mice treated daily with Glasdegib (PF-04449913) compared with vehicle treated controls have a significant spleen weight reduction (p=0.006). This reduction in leukemic burden corresponded with decreased GLI2 protein expression, as determined by both nanoproteomic analysis of FACS purified human progenitors and GLI2 confocal fluorescence microscopic analysis of splenic sections [1] .
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
In Vivo
Human BC LSC engrafted RAG2 -/- γ C -/- mice treated daily with Glasdegib (PF-04449913) compared with vehicle treated controls had a significant spleen weight reduction (p=0.006). When 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. These results highlight the important niche dependent effects of selective SMO inhibition that induce GLI2 downregulation in a cell type and context specific manner [1] .
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
Clinical Trial
| NCT Number | Sponsor | Condition | Start Date | Phase |
|---|---|---|---|---|
| NCT02038777 | Pfizer |
Acute Myeloid Leukemia
|
March 25, 2014 | Phase 1 |
| NCT01842646 | H. Lee Moffitt Cancer Center and Research Institute|Pfizer |
Myelodysplastic Syndrome (MDS)|Chronic Myelomonocytic Leukemia (CMML)
|
August 29, 2013 | Phase 2 |
| NCT03416179 | Pfizer |
Leukemia, Myeloid, Acute
|
April 20, 2018 | Phase 3 |
| NCT03270878 | Pfizer |
Healthy Volunteer Study
|
September 7, 2017 | Phase 1 |
| NCT04093505 | University Hospital Heidelberg |
Acute Myeloid Leukemia
|
April 1, 2021 | Phase 3 |
| NCT04051996 | Yale University|Pfizer |
ACUTE MYELOID LEUKEMIA
|
December 6, 2019 | Phase 2 |
| NCT02110342 | Pfizer |
Healthy
|
May 2014 | Phase 1 |
| NCT04230564 | Pfizer |
Leukemia, Myeloid, Acute
|
October 31, 2020 | |
| NCT04842604 | Pfizer |
Acute Myeloid Leukemia|Myelodysplastic Syndrome|Chronic Myelomonocytic Leukemia
|
May 17, 2021 | Phase 3 |
| NCT03130556 | Pfizer |
Healthy Volunteers
|
May 1, 2017 | Phase 1 |
| NCT01286467 | Pfizer |
Solid Tumors
|
May 2011 | Phase 1 |
| NCT03415867 | Grupo Espanol de trasplantes hematopoyeticos y terapia celular |
Sclerodermoid Chronic Graft-Versus-Host Disease (Disorder)
|
January 9, 2018 | Phase 1|Phase 2 |
| NCT02367456 | Pfizer |
Myelodysplastic Syndrome|Acute Myeloid Leukemia|Chronic Myelomonocytic Leukemia
|
April 28, 2015 | Phase 1 |
| NCT04231851 | University of California, Irvine|Jazz Pharmaceuticals|Pfizer |
Acute Myelogenous Leukemia (AML) Due to Therapy|Acute Myeloid Leukemia With Myelodysplasia-Related Changes
|
February 19, 2020 | Phase 2 |
| NCT03627754 | Pfizer |
Hepatic Impairment
|
November 5, 2018 | Phase 1 |
| NCT03162900 | Pfizer |
Healthy Volunteers
|
June 9, 2017 | Phase 1 |
| NCT04168502 | Gruppo Italiano Malattie EMatologiche dell´Adulto |
Acute Myeloid Leukemia
|
September 24, 2020 | Phase 3 |
| NCT02226172 | Pfizer |
Primary Myelofibrosis; Post-polycythemia Vera Myelofibrosis; Post-essential Thrombocythemia Myelofibrosis
|
October 6, 2014 | Phase 2 |
| NCT02430545 | Pfizer |
Healthy Volunteers
|
May 2015 | Phase 1 |
| NCT03596567 | Pfizer |
Renal Impairment
|
May 17, 2018 | Phase 1 |
| NCT01546038 | Pfizer |
Acute Myeloid Leukemia
|
June 27, 2012 | Phase 2 |
| NCT01841333 | University of Colorado, Denver|The Leukemia and Lymphoma Society |
Adult Acute Myeloid Leukemia in Remission|Recurrent Adult Acute Myeloid Leukemia
|
April 29, 2013 | Phase 2 |
| NCT00953758 | Pfizer |
Hematologic Malignancies
|
March 2010 | Phase 1 |
| NCT04111497 | Fred Hutchinson Cancer Center|Pfizer |
Chronic Graft Versus Host Disease|Fasciitis
|
December 3, 2019 | Phase 1|Phase 2 |
| NCT03226418 | University of Nebraska|National Cancer Institute (NCI) |
Adult Acute Myeloid Leukemia|Secondary Acute Myeloid Leukemia|Therapy-Related Acute Myeloid Leukemia
|
July 7, 2017 | Phase 2 |
| NCT03390296 | M.D. Anderson Cancer Center|National Cancer Institute (NCI) |
Recurrent Acute Myeloid Leukemia|Refractory Acute Myeloid Leukemia
|
December 27, 2017 | Phase 1|Phase 2 |
| NCT03466450 | Grupo Español de Investigación en Neurooncología |
Glioblastoma
|
March 15, 2018 | Phase 1|Phase 2 |
| NCT04655391 | City of Hope Medical Center|National Cancer Institute (NCI) |
Recurrent Acute Myeloid Leukemia
|
June 25, 2022 | Phase 1 |
| NCT03784014 | Institut National de la Santé Et de la Recherche Médicale, France|Commissariat A L´energie Atomique|Institut Bergonié|Plateforme labellisée Inca - Institut Bergonié, Bordeaux|Plateforme labellisée Inca - Hôpital Européen Georges Pompidou, Paris|EUCLID Clinical Trial Platform |
Soft Tissue Sarcoma
|
October 19, 2019 | Phase 3 |
Appearance
Solid
Shipping
Room temperature in continental US; may vary elsewhere.
Storage
| Powder | -20°C | 3 years |
|---|---|---|
| 4°C | 2 years | |
| In solvent | -80°C | 6 months |
| -20°C | 1 month |
Solvent & Solubility
DMSO : ≥ 83.33 mg/mL ( 222.55 mM )
* "≥" means soluble, but saturation unknown.
Stock Solutions
| Concentration Solvent Mass | 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 |
Synonyms