PHT-427 (CS-0223)

Alias: PHT427; PHT-427; PHT 427
Cat No.:V0165 Purity: ≥98%
PHT-427(CS0223) is a novel, potent, orally bioactive and dual inhibitor of Akt and PDPK1 (PtdIns dependent protein kinase-1) with potential anticancer activity.
PHT-427 (CS-0223) Chemical Structure CAS No.: 1191951-57-1
Product category: Akt
This product is for research use only, not for human use. We do not sell to patients.
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Purity & Quality Control Documentation

Purity: ≥98%

Product Description
PHT-427 (CS0223) is a novel, potent, orally bioactive and dual inhibitor of Akt and PDPK1 (PtdIns dependent protein kinase-1) with potential anticancer activity. With Kis of 2.7 μM and 5.2 μM, respectively, it binds with high affinity to the pleckstrin homology (PH) domains of Akt and PDPK1. Cancer cell proliferation and survival pathways are crucially activated by PDPK1/Akt signaling. As a novel PH domain binding inhibitor of PDPK1/Akt signaling, PHT-427 has significant in vivo antitumor activity and low toxicity.
Biological Activity I Assay Protocols (From Reference)
Targets
Akt (Ki = 2.7 μM); PDPK1 (Ki= 5.2 μM); PDK3 (IC50= 313 nM)
ln Vitro
PH-427 is a pleckstrin homology domain inhibitor to Akt/PDPK1. PHT-427 can inhibit both Akt and PDPK1 because it significantly lowers phospho-Ser241-PDPK1 and phospho-Thr308-Akt in PC-3 prostate cancer cells at 10 μM. Additionally, PHT-427 prevents the PH domains of Akt and PDPK1 from moving through the plasma membrane. [1] In BxPC-3 cells, PHT-427 induces apoptosis and inhibits AKT phosphorylation with an IC50 of 8.6 μM, primarily on its Ser473 residue and less strongly on its Thr308 residue, without changing the expression of the entire Akt protein. With an IC50 of 65 M, PHT-427 also exhibits antiproliferation in Panc-1 cells.[2]
ln Vivo
PHT-427 shows great antitumor activity in BxPC-3 pancreatic, MCF-7 breast and A-549 NSCL cancer xenografts. At doses of 125 to 250 mg/kg, PHT-427 inhibits the growth of tumors in BxPC-3 by up to 80%.[1]
Enzyme Assay
All interaction analyses are performed with a Biacore 2000, Biacore 2000 Control Software v3.2, and BIAevaluation v4.1 The Amine Coupling Kit from Biacore is used to immobilize the PH domain GST-fusion proteins (Akt1, IRS1, and PDK1) to a level of 10,000 Response Units (RUs) on a CM5 Sensorchip. High flow rates (30 L/min) are used to inject small molecule analytes at concentrations ranging from 0.1 to 10 the predicted KD. All samples and the running buffer have DMSO concentrations of 1% (v/v) or less.
Cell Assay
Serum-starved Panc-1 cells in phenol red-free growth medium are grown on glass-bottom 96-well imaging plates for 16 hours after being transfected with GFP-tagged Akt or PDKP1 PH domains. Following a 4-hour period of PI-103 or PHT-427 treatment, they are stimulated with 50 ng/mL IGF-1 for 10 minutes. Images are captured using an IN Cell Analyzer 1000 instrument with a Nikon Plan Fluor ELWD 20X/0.45 objective loaded and a 300msec exposure time before and after IGF-1 treatment[1].
Animal Protocol
Mice: PHT-427 is given orally once to female C57Bl/6 mice at a dose of 200 mg/kg. Three mice are taken out at a time, blood is collected into heparinized tubes, plasma is prepared, and the tubes are frozen at -80°C. 0.2 mL of plasma and 0.1 M sodium phosphate buffer, pH 4.0, are combined for the assay, and the mixture is then extracted for 1 hour by inversion with 1 mL of ethyl acetate. After centrifugation 0.8 mL of the organic layer is removed, evaporated under N2 and redissolved in 0.2 mL ethanol and 10 µL injected onto a Waters Quattro Ultima tandem mass spectrometer using a Phenomenex Luna 3.0 µm, 2.0×50 mm C8 analytical column with detection and quantification by multiple reaction monitoring with the mass spectrometer operating in electrospray positive ionization mode.
References

[1]. Mol Cancer Ther. 2010 Mar; 9(3): 706–717.

[2]. Cancer Res . 2009 Jun 15;69(12):5073-81.

These protocols are for reference only. InvivoChem does not independently validate these methods.
Physicochemical Properties
Molecular Formula
C20H31N3O2S2
Molecular Weight
409.61
Exact Mass
409.18577
Elemental Analysis
C, 58.64; H, 7.63; N, 10.26; O, 7.81; S, 15.66
CAS #
1191951-57-1
Appearance
Solid powder
SMILES
CCCCCCCCCCCCC1=CC=C(C=C1)S(=O)(=O)NC2=NN=CS2
InChi Key
BYWWNRBKPCPJMG-UHFFFAOYSA-N
InChi Code
InChI=1S/C20H31N3O2S2/c1-2-3-4-5-6-7-8-9-10-11-12-18-13-15-19(16-14-18)27(24,25)23-20-22-21-17-26-20/h13-17H,2-12H2,1H3,(H,22,23)
Chemical Name
4-dodecyl-N-(1,3,4-thiadiazol-2-yl)benzenesulfonamide
Synonyms
PHT427; PHT-427; PHT 427
HS Tariff Code
2934.99.9001
Storage

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Shipping Condition
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
Solubility Data
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
 (Please use freshly prepared in vivo formulations for optimal results.)
Preparing Stock Solutions 1 mg 5 mg 10 mg
1 mM 2.4413 mL 12.2067 mL 24.4135 mL
5 mM 0.4883 mL 2.4413 mL 4.8827 mL
10 mM 0.2441 mL 1.2207 mL 2.4413 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.

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Working concentration mg/mL;

Method for preparing DMSO stock solution mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.

Method for preparing in vivo formulation:Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O,mix and clarify.

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Biological Data
  • PHT-427

    Effects of PHT-427 in cells. Cancer Res, 2009, 69(12), 5073-5081.




  • PHT-427

    Antitumor activity of PHT-427 analogs

  • PHT-427

    In vivo effects of PHT-427

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