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PHT-427

Cat. No. M1900
PHT-427 Structure
Size Price Availability Quantity
25mg USD 130 In stock
50mg USD 220 In stock
100mg USD 375 In stock
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Quality Control
  • Current batch:
  • Purity >99%
  • COA
  • MSDS
Biological Activity

PHT-427 is a novel small-molecule inhibitor of PDPK1/Akt signaling with significant antitumor activity and minimal toxicity in vivo. The phosphatidylinositol 3-kinase/AKT signaling pathway plays a critical role in activating survival and antiapoptotic pathways within cancer cells. PHT-427 binds selectively to the PH domain of AKT, causing apoptosis at low micromolar concentrations. And it also binds to the PH domain of PDPK1. PHT-427 inhibited Akt and PDPK1 signaling and their downstream targets in sensitive but not resistant cells and tumor xenografts. PHT-427 induces apoptosis (IC50 = 6.3 μM), mainly on Akt Ser473 residue and less strongly on the Akt Thr308 residue without affecting total Akt protein expression. PHT-427 also shows antiproliferation in Panc-1 cells (IC50 = 65 μM).

Protocol
Cell Experiment
Cell lines Human MiaPaCa-2, BxPC-3, and Panc-1 pancreatic cancer cells
Preparation method Cell cytotoxicity assay
Cell growth inhibition was determined using a micro-cytoxicity assay. Cells were plated in 96-well micro-cytoxicity at 5,000–10,000 cells per well (depending on cell doubling time) and grown for 7 days. Compounds dissolved in DMSO were added directly to the media, at various concentrations ranging from 1 to 50 μM. The endpoint was spectrophotometric determination of the protein content of each well using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide. A concentration-response relationship at two or more concentration levels was used to obtain an IC50 for the compound.
Concentrations 1~50 μM
Incubation time 48 h
Animal Experiment
Animal models BxPC-3, Panc-1, MiaPaCa-2, PC-3, SKOV-3, A-549 or MCF-7 cells tumour model in female scid mice
Formulation 40 to 50 mg/ml in sesame seed oil
Dosages 200 mg/kg twice daily for 10 days
Administration oral
Conversion of different model animals based on BSA (Value based on data from FDA Draft Guidelines)
Species Mouse Rat Rabbit Guinea pig Hamster Dog
Weight (kg) 0.02 0.15 1.8 0.4 0.08 10
Body Surface Area (m2) 0.007 0.025 0.15 0.05 0.02 0.5
Km factor 3 6 12 8 5 20
Animal A (mg/kg) = Animal B (mg/kg) multiplied by  Animal B Km
Animal A Km

For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.

Chemical Information
Molecular Weight 409.61
Formula C20H31N3O2S2
CAS Number 1191951-57-1
Purity >99%
Solubility DMSO 80 mg/mL
Storage at -20°C
References

Molecular pharmacology and antitumor activity of PHT-427, a novel Akt/phosphatidylinositide-dependent protein kinase 1 pleckstrin homology domain inhibitor.
Meuillet EJ, et al. Mol Cancer Ther. 2010 Mar;9(3):706-17. PMID: 20197390.

In vitro and in vivo activity of novel small-molecule inhibitors targeting the pleckstrin homology domain of protein kinase B/AKT.
Moses SA, et al. Cancer Res. 2009 Jun 15;69(12):5073-81. PMID: 19491272.

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  Catalog
Abmole Inhibitor Catalog 2017




Keywords: PHT-427 supplier, Akt, inhibitors

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