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> Glasdegib [1095173-27-5]

Glasdegib [1095173-27-5]

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Referentie HY-16391-10mg

Formaat : 10mg

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Glasdegib (PF-04449913) is a potent and orally bioavailable smoothened inhibitor. Glasdegib (PF-04449913) binds to human SMO (amino acids 181-787) with an IC50 of 4 nM.

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Glasdegib Chemical Structure

Glasdegib Chemical Structure

CAS No. : 1095173-27-5

This product is a controlled substance and not for sale in your territory.

Based on 4 publication(s) in Google Scholar

Other Forms of Glasdegib:

  • Glasdegib maleate Obtenir un devis
Description

Glasdegib (PF-04449913) is a potent and orally bioavailable smoothened inhibitor. Glasdegib (PF-04449913) binds to human SMO (amino acids 181-787) with an IC50 of 4 nM[1].

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 IC50 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-/-γC-/- 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].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Glasdegib Related Antibodies
In Vivo

Human BC LSC engrafted RAG2-/-γC-/- 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].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
Essai clinique
Masse moléculaire

374.44

Formule

C21H22N6O
CAS No.

1095173-27-5
Unlabeled CAS

Appearance

Solid

Color

White to off-white

SMILES

O=C(NC1=CC=C(C#N)C=C1)N[C@H]2C[C@H](C3=NC4=CC=CC=C4N3)N(C)CC2
Livraison

Room temperature in continental US; may vary elsewhere.
Stockage
Powder -20°C 3 years
4°C 2 years
In solvent -80°C 2 years
-20°C 1 year
Solvant et solubilité
In Vitro: 

DMSO : 62.5 mg/mL (166.92 mM; ultrasonic and warming and heat to 60°C; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)

Preparing
Stock Solutions
Concentration Solvent Mass 1 mg 5 mg 10 mg
1 mM 2.6707 mL 13.3533 mL 26.7066 mL
5 mM 0.5341 mL 2.6707 mL 5.3413 mL
View the Complete Stock Solution Preparation Table

* Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.

  • Calculateur de molarité

  • Calculateur de dilution

Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)

Mass
=
Concentration
×
Volume
×
Molecular Weight *

Concentration (start) × Volume (start) = Concentration (final) × Volume (final)

This equation is commonly abbreviated as: C1V1 = C2V2

Concentration (start)

C1

×
Volume (start)

V1

=
Concentration (final)

C2

×
Volume (final)

V2

In Vivo:

Select the appropriate dissolution method based on your experimental animal and administration route.

For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for in vivo experiments, it is recommended to prepare freshly and use it on the same day.
The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.

  • Protocol 1

    Add each solvent one by one:  10% DMSO    40% PEG300    5% Tween-80    45% Saline

    Solubility: ≥ 2.08 mg/mL (5.55 mM); Clear solution

    This protocol yields a clear solution of ≥ 2.08 mg/mL (saturation unknown).

    Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (20.8 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.

    Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
  • Protocol 2

    Add each solvent one by one:  10% DMSO    90% (20% SBE-β-CD in Saline)

    Solubility: ≥ 2.08 mg/mL (5.55 mM); Clear solution

    This protocol yields a clear solution of ≥ 2.08 mg/mL (saturation unknown).

    Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (20.8 mg/mL) to 900 μL 20% SBE-β-CD in Saline, and mix evenly.

    Preparation of 20% SBE-β-CD in Saline (4°C, storage for one week): 2 g SBE-β-CD powder is dissolved in 10 mL Saline, completely dissolve until clear.
In Vivo Dissolution Calculator
Please enter the basic information of animal experiments:

Dosage

mg/kg

Animal weight
(per animal)

g

Dosing volume
(per animal)

μL

Number of animals

Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Please enter your animal formula composition:
%
DMSO +
% 
+
%
Tween-80 +
%
Saline
Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).
Calculation results:
Working solution concentration: mg/mL
Method for preparing stock solution: mg drug dissolved in μL  DMSO (Stock solution concentration: mg/mL).
The concentration of the stock solution you require exceeds the measured solubility. The following solution is for reference only. If necessary, please contact MedChemExpress (MCE).
Method for preparing in vivo working solution for animal experiments: Take μL DMSO stock solution, add μL . μL , mix evenly, next add μL Tween 80, mix evenly, then add μL Saline.
 If the continuous dosing period exceeds half a month, please choose this protocol carefully.
Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.
Pureté et documentation

Purity: 99.31%

COA (246 KB) HNMR (189 KB) LCMS (303 KB)

Instruction de manipulation (2659 KB)
Références

  • [1]. Sadarangani A, et al. GLI2 inhibition abrogates human leukemia stem cell dormancy. J Transl Med. 2015 Mar 21;13:98.  [Content Brief]

Test cellulaire
[1]

Normal or BC CML CD34+ cells are treated with vehicle, Glasdegib (PF-04449913) (1 μM), BMS-354825 (50 nM), or combination treatment. Mouse bone marrow stromal cell lines, M2-10B4 (M2) and SL/SL (SL) are 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 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 and quantified by weekly FACS analysis[1].

MCE n'a pas confirmé de manière indépendante l'exactitude de ces méthodes. Ils sont pour référence seulement.
Administration animale
[1]

Mice[1]
RAG2-/-c-/- mice are transplanted intrahepatically with equal numbers of normal progenitors or BC LSC. Upon detection of human CD45+ cell peripheral blood engraftment, mice are treated daily by oral gavage with vehicle (50% 1,2 Propandiol, 50% HBSS or methylcellulose), Glasdegib (100 mg/kg), BMS-354825 (50 mg/kg), or the combination for 14 days followed by FACS to quantify human engraftment in hematopoietic niches. To assess effects on normal HSC function, 7 to 10 week old NOD. Cg-PrkdcSCID IL2R1Wjl/SzJ mice are sublethally irradiated, transplanted retro-orbitally with 100,000 CD34+ human cord blood cells and treated 8 weeks later with vehicle or Glasdegib (100 mg/kg) for 14 days followed by FACS engraftment analysis.

MCE n'a pas confirmé de manière indépendante l'exactitude de ces méthodes. Ils sont pour référence seulement.
Références

  • [1]. Sadarangani A, et al. GLI2 inhibition abrogates human leukemia stem cell dormancy. J Transl Med. 2015 Mar 21;13:98.  [Content Brief]

  • [1]. Sadarangani A, et al. GLI2 inhibition abrogates human leukemia stem cell dormancy. J Transl Med. 2015 Mar 21;13:98.

Complete Stock Solution Preparation Table

* Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.

Optional Solvent Concentration Solvent Mass 1 mg 5 mg 10 mg 25 mg
DMSO 1 mM 2.6707 mL 13.3533 mL 26.7066 mL 66.7666 mL
5 mM 0.5341 mL 2.6707 mL 5.3413 mL 13.3533 mL
10 mM 0.2671 mL 1.3353 mL 2.6707 mL 6.6767 mL
15 mM 0.1780 mL 0.8902 mL 1.7804 mL 4.4511 mL
20 mM 0.1335 mL 0.6677 mL 1.3353 mL 3.3383 mL
25 mM 0.1068 mL 0.5341 mL 1.0683 mL 2.6707 mL
30 mM 0.0890 mL 0.4451 mL 0.8902 mL 2.2256 mL
40 mM 0.0668 mL 0.3338 mL 0.6677 mL 1.6692 mL
50 mM 0.0534 mL 0.2671 mL 0.5341 mL 1.3353 mL
60 mM 0.0445 mL 0.2226 mL 0.4451 mL 1.1128 mL
80 mM 0.0334 mL 0.1669 mL 0.3338 mL 0.8346 mL
100 mM 0.0267 mL 0.1335 mL 0.2671 mL 0.6677 mL
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Glasdegib Related Classifications

Help & FAQs

Keywords:

Glasdegib1095173-27-5PF-04449913PF04449913PF 04449913SmoSmoothenedInhibitorinhibitorinhibit

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