10mM in DMSO for sensitive chromatographic and analytical workflows requiring minimal baseline interference.
Store at -80°C Ships Dry ice packs + Cold packs Check lot-specific COA for exact specifications.
SDS, COA, datasheet, and spec sheet available for download. Lot-specific COA accessible via lot number lookup.
Cited in 0 peer-reviewed publications across chromatography, organic synthesis, and cross-coupling reactions.
Information
PF-5274857 is a potent and selectiveSmoothened (Smo)antagonist, inhibitsHedgehog(Hh) signaling withIC50andKiof 5.8 nM and 4.6 nM, respectively, and can penetrate the blood–brain barrier.
In vitro
PF-5274857 completely inhibits Shh-induced Hh pathway activity with IC50 of 2.7 nM measured by the transcriptional activity of Smo downstream gene Gli1 in MEF cells. The μ-opioid receptor is weakly inhibited by PF-5274857 with a dissociation constant of 36 μM subsequently determined in a functional assay.
In vivo
PF-5274857 shows significant dose-dependent tumor growth inhibition (TGI) and induces tumor regression at high doses(>10 mg/kg)., PF-5274857 downregulates Gli1, Gli2, Ptch1, and Ptch2 gene expression levels to various degrees with maximal effects being achieved between 6 and 12 hours post-dose (Gli1 is the most sensitive gene), whereas PF-5274857 has little effect on Smo levels. In skin tissue, downregulation of Gli1 and Gli2 is also observed with a similar time course by PF-5274857. The model-derived drug concentration for half maximal inhibition of the tumor Gli1 mRNA production rate (IC50) by PF-5274857 is determined to be 8.9 nM in the Ptch+/−p53+/− medulloblastoma allograft mice, which mathematically corresponds to tumor regression of 119% TGI after 6 days of plasma exposure at this concentration. In the Ptch+/−p53−/− medulloblastoma allograft mice, the IC50 value is estimated to be 3.5 nM, consistent with the Ptch+/−p53+/− results. PF-5274857 is also able to cross the blood–brain barrier in rats within 4 hours post-dose.
Cell Data
cell lines：SW48, Colo 201, SW480, WiDr, Colo205, RKO E6, RKO, LoVo, HCT-116, SW620, HT29, W1417, DLD-1, HCT-8, Colo 320HSR, Hep-3B, OVCAR-3, MEC-1 cells
Concentrations：50 pM- 3 μM
Incubation Time：48 hours
Powder Purity:≥97%
| Isomere SMILES | CC1=CC(=C(N=C1)C2=CC(=NC=C2Cl)N3CCN(CC3)C(=O)CCS(=O)(=O)C)C |
|---|---|
| Molekulargewicht | 436.96 |
| Reaxy-Rn | 22484866 |
| Reaxys-RN_link_address | https://www.reaxys.com/reaxys/secured/hopinto.do?context=S&query=IDE.XRN=22484866&ln= |
Comprehensive hazard, handling, storage, and regulatory compliance document.
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View spec sheet →| Activity Type | Activity Value -log(M) | Mechanism of Action | Activity Reference | Publications (PubMed IDs) |
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| Löslichkeit | Solubility (25°C) In vitro DMSO: 57 mg/mL (197.71 mM); Ethanol: 15 mg/mL (52.02 mM); Water: Insoluble; |
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