PF-5274857
PF-5274857
CAS: 1373615-35-0
Molecular Formula: C20H25ClN4O3S
PF-5274857 - Names and Identifiers
| Name | PF-5274857 |
| Synonyms | CS-601 PF5274857 PF-5274857 PF 5274857 pf-5274857 PF-5274857 hydrochloride 1-[4-(5'-Chloro-3,5-dimethyl[2,4'-bipyridin]-2'-yl)-1-piperazinyl]-3-(methylsulfonyl)-1-propanone 1-(4-(5-chloro-4-(3,5-diMethylpyridin-2-yl)pyridin-2-yl)piperazin-1-yl)-3-(Methylsulfonyl)propan-1-one 1-[4-(5′-Chloro-3,5-dimethyl-2,4′-bipyridin-2′-yl)piperazin-1-yl] -3- (methylsulfonyl)propan-1-one hydrochloride |
| CAS | 1373615-35-0 |
| EINECS | 200-204-2 |
PF-5274857 - Physico-chemical Properties
| Molecular Formula | C20H25ClN4O3S |
| Molar Mass | 436.96 |
| Solubility | DMSO: Soluble( < 1 mg/ml refers to the product slightly soluble or insoluble) |
| Appearance | powder |
| Color | white to beige |
| Storage Condition | Sealed in dry,Store in freezer, under -20°C |
| Use | PF-5274857 is an effective and selective hedgehog signaling pathway inhibitor (IC50: 5.8 nM and a Ki: 4.6 nM). PF-5274857 is a potentially attractive clinical candidate for the treatment of tumor types including brain tumors and brain metastasis driven by an activated Hh pathway.PF-5274857 was found to effectively penetrate the blood-brain barrier and inhibit Smo activity in the brain of primary medulloblastoma mice, resulting in improved animal survival rates. PF-5274857 was orally available and metabolically stable in vivo. |
| In vitro study | The Ki of PF-5274857 is 4.6 nM. PF-5274857 can completely inhibit Shh-induced Hh pathway activity, and the IC50 is 2.7nM by measuring the transcriptional activity of Gli1, a gene downstream of Smo, in MEF cells. PF-5274857 binds to Smo with an IC50 of 5.8 nM. PF-5274857 inhibits μ-opioid receptors weakly and the dissociation constant was 36 μm in a subsequent functional analysis |
| In vivo study | PF-5274857 had a significant tumor growth inhibitory effect, with inhibition having a dose-dependent profile and inducing tumor regression after 6 days of treatment at high doses (> 10 mg/kg). The expression levels of Gli1, Gli2, Ptch1 and Ptch2 genes were adjusted by PF-5274857 in different degrees in tumor tissues, and the best effect was achieved 6 to 12 hours after administration, but PF-5274857 had no effect on Smo expression level. In skin tissue, PF-5274857 down-regulated Gli1 and Gli2 expression over a similar time course. The IC50 of PF-5274857 for inhibition of tumor Gli1 mRNA productivity in a Ptch +/− p53 +/− medulloblastoma allograft mouse model was 8.9 nM, this corresponds to a 119% inhibition of tumor growth after 6 days of treatment with the drug in plasma at this concentration. The IC50 value in the Ptch +/− p53 −/− medulloblastoma allograft mouse model is expected to be 3.5 nM, which is consistent with the results of the Ptch +/− p53 +/− model. |
PF-5274857 - Risk and Safety
| WGK Germany | 3 |
PF-5274857 - Reference
| Reference Show more | 1: Zhou WJ, Chen J, Feng Y, Fan YP, Li Q, Fu J, Zhang P. [Inhibition of Cigarettes Smoke-induced Epithelial to Mesenchymal Transition by the SMO Inhibitor PF-5274857 in Beas-2b Epithelial Cells]. Sichuan Da Xue Xue Bao Yi Xue Ban. 2016 Jul;47(4):485-490. Chinese. PubMed PMID: 28591947. 2: Lauressergues E, Heusler P, Lestienne F, Troulier D, Rauly-Lestienne I, Tourette A, Ailhaud MC, Cathala C, Tardif S, Denais-Laliève D, Calmettes MT, Degryse AD, Dumoulin A, De Vries L, Cussac D. Pharmacological evaluation of a series of smoothened antagonists in signaling pathways and after topical application in a depilated mouse model. Pharmacol Res Perspect. 2016 Mar 4;4(2):e00214. doi: 10.1002/prp2.214. eCollection 2016 Apr. PubMed PMID: 27069629; PubMed Central PMCID: PMC4804317. 3: Rohner A, Spilker ME, Lam JL, Pascual B, Bartkowski D, Li QJ, Yang AH, Stevens G, Xu M, Wells PA, Planken S, Nair S, Sun S. 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. doi: 10.1158/1535-7163.MCT-11-0691. Epub 2011 Nov 14. PubMed PMID: 22084163. |
PF-5274857 - Preparation solution concentration reference
| 1mg | 5mg | 10mg | |
|---|---|---|---|
| 1 mM | 2.289 ml | 11.443 ml | 22.885 ml |
| 5 mM | 0.458 ml | 2.289 ml | 4.577 ml |
| 10 mM | 0.229 ml | 1.144 ml | 2.289 ml |
| 5 mM | 0.046 ml | 0.229 ml | 0.458 ml |
Last Update：2024-01-02 23:10:35
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