PF-04449913 (Synonyms: Glasdegib) |
| カタログ番号GC16230 |
PF-04449913 (PF-04449913) は、経口で生物学的に利用可能な強力な平滑化阻害剤です。 PF-04449913 (PF-04449913) は、4 nM の IC50 でヒト SMO (アミノ酸 181-787) に結合します。
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 1095173-27-5
Sample solution is provided at 25 µL, 10mM.
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PF-04449913 is an orally bioavailable inhibitor of smoothened with IC50 value of 5nM [1].
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 [1].
PF-04449913 is found not to inhibit cytochrome P450 and is negative in Ames and micronucleus assays suggesting it as a safe drug. In the preclinical studies, PF-04449913 shows a half-life of 30 h and an oral bioavailability of 55% in humans. It also has low plasma clearance of 1.03 mL/min/kg and moderate volume of distribution (2.7 L/kg) [1].
References:
[1] Munchhof MJ, Li Q, Shavnya A, Borzillo GV, Boyden TL, Jones CS, LaGreca SD, Martinez-Alsina L, Patel N, Pelletier K, Reiter LA, Robbins MD, Tkalcevic GT. Discovery of PF-04449913, a Potent and Orally Bioavailable Inhibitor of Smoothened. ACS Med Chem Lett. 2011 Dec 21;3(2):106-11.
| Animal experiment [1]: | |
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Animal models |
Rats and dogs |
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Dosage form |
1 mg/kg and 0.5 mg/kg, Oral dosing |
|
Application |
In rats and dogs, PF-04449913 had high clearance in rat and low clearance in dog with CL of 31 and 3.9 mL/min/kg, respectively. The oral bioavailabilities of PF-04449913 in rat and dog were 33 and 68%, respectively. PF-04449913 had moderate volume distribution of 4.8 and 4.3 L/kg and t1/2 of 1.4 and 2.9 h, respectively. |
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Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
| Clinical Trial [2]: | |
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Disease models |
Patients with advanced solid tumors |
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Dosage form |
80 mg-640 mg, orally administered once daily, continuous 28-day |
|
Application |
In patients with advanced solid tumors, the first-cycle dose-limiting toxicity (DLT) rate at the 640 mg dose level was 33.3%, and the maximum tolerated dose (MTD) of PF-04449913 was estimated to be 320mg once daily. PF-04449913 was generally well tolerated at doses of 80 to 320 mg once daily. PF-04449913 modulated hedgehog signaling at the dose levels tested and downregulated GLI1 expression in the skin of patients by >80%. |
|
Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
|
References: [1] Munchhof MJ, Li Q, Shavnya A, Borzillo GV, Boyden TL, Jones CS, LaGreca SD, Martinez-Alsina L, Patel N, Pelletier K, Reiter LA, Robbins MD, Tkalcevic GT. Discovery of PF-04449913, a Potent and Orally Bioavailable Inhibitor of Smoothened. ACS Med Chem Lett. 2011 Dec 21;3(2):106-11. [2]. Wagner AJ1, Messersmith WA2, Shaik MN3, et al. A phase I study of PF-04449913, an oral hedgehog inhibitor, in patients with advanced solid tumors. Clin Cancer Res. 2015 Mar 1;21(5):1044-51. |
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| Cas No. | 1095173-27-5 | SDF | |
| 同義語 | Glasdegib | ||
| Chemical Name | 1-[(2R,4R)-2-(1H-benzimidazol-2-yl)-1-methylpiperidin-4-yl]-3-(4-cyanophenyl)urea | ||
| Canonical SMILES | CN1CCC(CC1C2=NC3=CC=CC=C3N2)NC(=O)NC4=CC=C(C=C4)C#N | ||
| Formula | C21H22N6O | M.Wt | 374.44 |
| 溶解度 | ≥ 20.15mg/mL in DMSO | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
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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 |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
g
μL
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Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid 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 master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 24 reference(s) in Google Scholar.)
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