product name PHT-427
Description: PHT-427 is a dual Akt and PDPK1 inhibitor (high affinity binding for the PH domains of Akt and PDPK1) with Ki of 2.7 μM and 5.2 μM, respectively. PHT-427 exhibits good oral anti-tumor activity in mouse xenograft models. PHT-427 reduces the phosphorylation of AKT and PDPK1. Following the administration of a single oral dose of PHT-427 to mice bearing BxPC-3 human pancreatic tumor xenografts, PHT-427 inhibited the phosphorylation of both Akt and PDPK1 as well as downstream targets maximally at 8–12 h after administration corresponding to its peak plasma concentration, with PDPK1 inhibition extending to 24 hr.
References: Mol Cancer Ther. 2010 Mar;9(3):706-17; Cancer Res. 2009 Jun 15;69(12):5073-81.
409.61
Formula
C20H31N3O2S2
CAS No.
1191951-57-1
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: 82 mg/mL (200.2 mM)
Water: <1 mg/mL
Ethanol: 60 mg/mL (146.5 mM)
Solubility (In vivo)
5% DMSO+95% Corn oil: 5mg/mL
Chemical Name
4-dodecyl-N-(1,3,4-thiadiazol-2-yl)benzenesulfonamide
other peoduct :References PubMed ID：:http://www.ncbi.nlm.nih.gov/pubmed/19394300
| In Vitro |
Kinase Assay: All interaction analyses are performed with a Biacore 2000, Biacore 2000 Control Software v3.2, and BIAevaluation v4.1 analysis software. The PH domain GST-fusion proteins (Akt1, IRS1, and PDK1) are immobilized on a CM5 Sensorchip using Biacores Amine Coupling Kit to a level of 10,000 Response units (RUs). Small molecule analytes at concentrations ranging from 0.1 to 10 × the predicted KD are injected at a high flow rate (30μL/min). DMSO concentrations in all samples and running buffer are 1% (v/v) or less. Cell Assay: PH-427 is a pleckstrin homology domain inhibitor to Akt/PDPK1. PH-427 significantly reduces phospho-Ser241-PDPK1 phospho-Thr308-Akt in PC-3 prostate cancer cells at 10 μM, which shows that PHT-427 could inhibit both Akt and PDPK1. PHT-427 also inhibits translocation of the Akt and PDPK1 PH domains in plasma membrane. PHT-427 induces apoptosis and inhibits AKT phosphorylation with IC50 of 8.6 μM (in BxPC-3 cells), which mainly on its Ser473 residue and less strongly on Thr308 residue without affecting total Akt protein expression. PHT-427 also shows antiproliferation in Panc-1 cells with IC50 of 65 μM. |
|---|---|
| In Vivo | PHT-427 shows great antitumor activity in BxPC-3 pancreatic, MCF-7 breast and A-549 NSCL cancer xenografts. PHT-427 gives up to an 80% inhibition of tumor growth in BxPC-3 at doses of 125 to 250 mg/kg. |
| Animal model | BxPC-3, Panc-1, MiaPaCa-2, PC-3, SKOV-3, A-549 or MCF-7 cells are injected subcutaneously into the flanks of female scid mice. |
| Formulation & Dosage | Formulated in 40 to 50 mg/mL in sesame seed oil; 125-250 mg/kg; oral gavage |
| References | [1] Meuillet EJ, et al. Mol Cancer Ther, 2010, 9(3), 706-717.; [2] Moses SA, et al. Cancer Res, 2009, 69(12), 5073-5081. |
Related Posts
product name PHT-427
Description: PHT-427 is a dual Akt and PDPK1 inhibitor (high affinity binding for the PH domains of Akt and PDPK1) with Ki of 2.7 μM and 5.2 μM, respectively. PHT-427 exhibits good oral anti-tumor activity in mouse xenograft models. PHT-427 reduces the phosphorylation of AKT and PDPK1. Following the administration of a single oral dose of PHT-427 to mice bearing BxPC-3 human pancreatic tumor xenografts, PHT-427 inhibited the phosphorylation of both Akt and PDPK1 as well as downstream targets maximally at 8–12 h after administration corresponding to its peak plasma concentration, with PDPK1 inhibition extending to 24 hr.
References: Mol Cancer Ther. 2010 Mar;9(3):706-17; Cancer Res. 2009 Jun 15;69(12):5073-81.
409.61
Formula
C20H31N3O2S2
CAS No.
1191951-57-1
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: 82 mg/mL (200.2 mM)
Water: <1 mg/mL
Ethanol: 60 mg/mL (146.5 mM)
Solubility (In vivo)
5% DMSO+95% Corn oil: 5mg/mL
Chemical Name
4-dodecyl-N-(1,3,4-thiadiazol-2-yl)benzenesulfonamide
other peoduct :References PubMed ID：:http://www.ncbi.nlm.nih.gov/pubmed/19394300
| In Vitro |
Kinase Assay: All interaction analyses are performed with a Biacore 2000, Biacore 2000 Control Software v3.2, and BIAevaluation v4.1 analysis software. The PH domain GST-fusion proteins (Akt1, IRS1, and PDK1) are immobilized on a CM5 Sensorchip using Biacores Amine Coupling Kit to a level of 10,000 Response units (RUs). Small molecule analytes at concentrations ranging from 0.1 to 10 × the predicted KD are injected at a high flow rate (30μL/min). DMSO concentrations in all samples and running buffer are 1% (v/v) or less. Cell Assay: PH-427 is a pleckstrin homology domain inhibitor to Akt/PDPK1. PH-427 significantly reduces phospho-Ser241-PDPK1 phospho-Thr308-Akt in PC-3 prostate cancer cells at 10 μM, which shows that PHT-427 could inhibit both Akt and PDPK1. PHT-427 also inhibits translocation of the Akt and PDPK1 PH domains in plasma membrane. PHT-427 induces apoptosis and inhibits AKT phosphorylation with IC50 of 8.6 μM (in BxPC-3 cells), which mainly on its Ser473 residue and less strongly on Thr308 residue without affecting total Akt protein expression. PHT-427 also shows antiproliferation in Panc-1 cells with IC50 of 65 μM. |
|---|---|
| In Vivo | PHT-427 shows great antitumor activity in BxPC-3 pancreatic, MCF-7 breast and A-549 NSCL cancer xenografts. PHT-427 gives up to an 80% inhibition of tumor growth in BxPC-3 at doses of 125 to 250 mg/kg. |
| Animal model | BxPC-3, Panc-1, MiaPaCa-2, PC-3, SKOV-3, A-549 or MCF-7 cells are injected subcutaneously into the flanks of female scid mice. |
| Formulation & Dosage | Formulated in 40 to 50 mg/mL in sesame seed oil; 125-250 mg/kg; oral gavage |
| References | [1] Meuillet EJ, et al. Mol Cancer Ther, 2010, 9(3), 706-717.; [2] Moses SA, et al. Cancer Res, 2009, 69(12), 5073-5081. |