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).
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 |
Molecular Weight | 409.61 |
Formula | C20H31N3O2S2 |
CAS Number | 1191951-57-1 |
Solubility (25°C) | DMSO 80 mg/mL |
Storage |
Powder -20°C 3 years ; 4°C 2 years In solvent -80°C 6 months ; -20°C 1 month |
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 Compound A used for a mouse (20 mg/kg) to a dose based on the BSA for a rat, multiply 20 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 Compound A of 10 mg/kg.
Related Akt Products |
---|
LY2780301
LY2780301 is an oral dual-target inhibitor of AKT/RSK that binds to and inhibits the activity of Akt, thereby inhibiting the PI3K/Akt signaling pathway, which in turn inhibits cell proliferation and induces apoptosis in tumor cells, and possesses antitumor activity. |
Akt/SKG Substrate Peptide
Akt/SKG Substrate Peptide is a synthetic peptide suitable as a substrate for Akt/PKB, which is not phosphorylated by p70S6K or MAPK1. |
Adropin (34-76) (human, mouse, rat)
Adropin (34-76) (human, mouse, rat) regulates fuel selection preferences in skeletal muscle. |
Apoptin-derived peptide
Apoptin-derived peptide is an antitumor polypeptide with cytotoxicity. |
TAT-TCL1-Akt-in
TAT-TCL1-Akt-in is an Akt inhibitor. |
Products are for research use only. Not for human use. We do not sell to patients.
© Copyright 2010-2023 AbMole BioScience. All Rights Reserved.