| Size | Price | |
|---|---|---|
| 500mg | ||
| 1g | ||
| Other Sizes |
| Targets |
IC50: 5.8 nM (Smo); Ki: 4.6 nM (Smo)[1]
|
|---|---|
| ln Vitro |
The transcriptional activity of Smo downstream gene Gli1 in MEF cells indicates that PF-5274857 totally suppresses Shh-induced Hh pathway activity, with an IC50 of 2.7±1.4 nM[1]. When used at 1 μM, PF-5274857 exhibits less than 20% inhibition against a wide range of protein kinases[1].
|
| ln Vivo |
In medulloblastoma allograft mouse models, PF-5274857 (1-30 mg/kg; po once daily for 6 days) demonstrates strong antitumor efficaciousness and association between PK and PD[1]. In rats, PF-5274857 (10 mg/kg; ih) in the plasma can pass through the blood-brain barrier four hours after administration[1]. Targeting Smo in the brain, PF-5274857 (10–100 mg/kg; po once daily for 4 days) can cause the brain tumor's Hh pathway activity to be downregulated[1]. Mice with primary Ptch+/− p53−/− medulloblastoma have higher survival rates when treated with PF-5274857 (30 mg/kg; po once daily for 34 days)[1]. (5-30 mg/kg; po) has a half-life (T1/2) of 1.7±0.1 hours and an apparent volume of distribution of 5.6±0.5 L/kg[1].
|
| Animal Protocol |
Animal/Disease Models: Severe combined immunodeficient (SCID )-beige mice (6-8 weeks old) are genetically engineered[1]
Doses: 0, 1, 5, 10, 30 mg/kg Route of Administration: Po one time/day for 6 days Experimental Results: demonstrated robust antitumor activity with an in vivo IC50 of 8.9±2.6 nM. Animal/Disease Models: Severe combined immunodeficient (SCID)-beige mice (6-8 weeks old)[1] Doses: 0, 5, 10, 30 mg/kg (pharmacokinetic/PK Analysis) Route of Administration: A single po Experimental Results: The apparent volume of distribution of 5.6±0.5 L/kg; the half-life (T1/2) of 1.7±0.1 hrs (hours). |
| References |
[1]. Rohner A, et, al. Effective targeting of Hedgehog signaling in a medulloblastoma model with PF-5274857, a potent and selective Smoothened antagonist that penetrates the blood-brain barrier. Mol Cancer Ther. 2012 Jan;11(1):57-65.
|
| Molecular Formula |
C20H26CL2N4O3S
|
|---|---|
| Molecular Weight |
473.42
|
| Exact Mass |
472.11
|
| CAS # |
1613439-62-5
|
| Related CAS # |
PF-5274857;1373615-35-0
|
| PubChem CID |
90489027
|
| Appearance |
Typically exists as solid at room temperature
|
| Hydrogen Bond Donor Count |
1
|
| Hydrogen Bond Acceptor Count |
6
|
| Rotatable Bond Count |
5
|
| Heavy Atom Count |
30
|
| Complexity |
663
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
ClC1=CN=C(C=C1C1C(C)=CC(C)=CN=1)N1CCN(C(CCS(C)(=O)=O)=O)CC1.Cl
|
| InChi Key |
GULNFUQAVPTTQV-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C20H25ClN4O3S.ClH/c1-14-10-15(2)20(23-12-14)16-11-18(22-13-17(16)21)24-5-7-25(8-6-24)19(26)4-9-29(3,27)28;/h10-13H,4-9H2,1-3H3;1H
|
| Chemical Name |
1-[4-[5-chloro-4-(3,5-dimethylpyridin-2-yl)pyridin-2-yl]piperazin-1-yl]-3-methylsulfonylpropan-1-one;hydrochloride
|
| HS Tariff Code |
2934.99.9001
|
| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
|
| Solubility (In Vitro) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
|
|---|---|
| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.1123 mL | 10.5614 mL | 21.1229 mL | |
| 5 mM | 0.4225 mL | 2.1123 mL | 4.2246 mL | |
| 10 mM | 0.2112 mL | 1.0561 mL | 2.1123 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.
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