PHT-427
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    WARNING: This product is for research use only, not for human or veterinary use.

MedKoo CAT#: 401705

CAS#: 1191951-57-1

Description: PHT-427 is an AKT inhibitor that inhibits AKT and PDPK1 at low micromolar concentrations in numerous cancer cell lines and 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.

Chemical Structure

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PHT-427
CAS# 1191951-57-1
Product data Instruction

Theoretical Analysis

MedKoo Cat#: 401705
Name: PHT-427
CAS#: 1191951-57-1
Chemical Formula: C20H31N3O2S2
Exact Mass: 409.19
Molecular Weight: 409.609
Elemental Analysis: C, 58.64; H, 7.63; N, 10.26; O, 7.81; S, 15.66

Price and Availability

Size Price Availability Quantity
10mg USD 150
25mg USD 250
50mg USD 450
100mg USD 800 2 Weeks
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Synonym: PHT427; PHT-427; PHT 427.

IUPAC/Chemical Name: 4-dodecyl-N-(1,3,4-thiadiazol-2-yl)benzenesulfonamide

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)

SMILES Code: O=S(C1=CC=C(CCCCCCCCCCCC)C=C1)(NC2=NN=CS2)=O

Appearance: Solid powder

Purity: >98% (or refer to the Certificate of Analysis)

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years)

Solubility: soluble in DMSO, not soluble in water.

Shelf Life: >5 years if stored properly

Drug Formulation: This drug may be formulated in DMSO

Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code: 2934.99.9001

More Info: PHT-427 was found to bound with the highest affinity to the PH domains of both PDPK1 and Akt. PHT-427 inhibited Akt and PDPK1 signaling and their downstream targets in sensitive but not resistant cells and tumor xenografts. When given orally, PHT-427 inhibited the growth of human tumor xenografts in immunodeficient mice, with up to 80% inhibition in the most sensitive tumors, and showed greater activity than analogues with C4, C6, or C8 alkyl chains. Inhibition of PDPK1 was more closely correlated to antitumor activity than Akt inhibition. Tumors with PIK3CA mutation were the most sensitive, and K-Ras mutant tumors were the least sensitive. Combination studies showed that PHT-427 has greater than additive antitumor activity with paclitaxel in breast cancer and with erlotinib in non-small cell lung cancer. When given >5 days, PHT-427 caused no weight loss or change in blood chemistry. Thus, we report a novel PH domain binding inhibitor of PDPK1/Akt signaling with significant in vivo antitumor activity and minimal toxicity.  (source: Mol Cancer Ther. 2010 Mar;9(3):706-17.)    

Product Data:
Product Data
Instruction:
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Biological target: PHT-427 is an inhibitor of the pleckstrin homology (PH) domain of Akt, and it is also an inhibitor of PDPK1 with Kis of 2.7 µM and 5.2 µM and for Akt and PDPK1.
In vitro activity: PHT427 was identified as an inhibitor of NDM-1. It could significantly inhibit the activity of NDM-1 with an IC50 of 1.42 μmol/L, and restored the susceptibility of meropenem against E. coli BL21(DE3)/pET30a(+)-bla NDM-1 and K. pneumoniae clinical strain C1928 (producing NDM-1) in vitro. The mechanism study indicated that PHT427 could act on the zinc ions at the active site of NDM-1 and the catalytic key amino acid residues simultaneously. Reference: Front Microbiol. 2023 Apr 17;14:1168052. https://pubmed.ncbi.nlm.nih.gov/37138606/
In vivo activity: PHT-427 itself (C-12 chain) bound with the highest affinity to the PH domains of both PDPK1 and Akt. PHT-427 inhibited Akt and PDPK1 signaling and their downstream targets in sensitive but not resistant cells and tumor xenografts. When given orally, PHT-427 inhibited the growth of human tumor xenografts in immunodeficient mice, with up to 80% inhibition in the most sensitive tumors, and showed greater activity than analogues with C4, C6, or C8 alkyl chains. Inhibition of PDPK1 was more closely correlated to antitumor activity than Akt inhibition. Reference: Mol Cancer Ther. 2010 Mar;9(3):706-17. https://pubmed.ncbi.nlm.nih.gov/20197390/

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMF 33.0 80.57
DMF:PBS (pH 7.2) (1:4) 0.2 0.49
DMSO 47.2 115.33

Preparing Stock Solutions

The following data is based on the product molecular weight 409.61 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Recalculate based on batch purity %
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 1.15 mL 5.76 mL 11.51 mL
5 mM 0.23 mL 1.15 mL 2.3 mL
10 mM 0.12 mL 0.58 mL 1.15 mL
50 mM 0.02 mL 0.12 mL 0.23 mL
Formulation protocol: 1. Li X, Wang Q, Zheng J, Guan Y, Liu C, Han J, Liu S, Liu T, Xiao C, Wang X, Liu Y. PHT427 as an effective New Delhi metallo-β-lactamase-1 (NDM-1) inhibitor restored the susceptibility of meropenem against Enterobacteriaceae producing NDM-1. Front Microbiol. 2023 Apr 17;14:1168052. doi: 10.3389/fmicb.2023.1168052. PMID: 37138606; PMCID: PMC10150926. 2. Yanes-Díaz J, Palao-Suay R, Aguilar MR, Riestra-Ayora JI, Ferruelo-Alonso A, Rojo Del Olmo L, Vázquez-Lasa B, Sanz-Fernández R, Sánchez-Rodríguez C. Antitumor Activity of Nanoparticles Loaded with PHT-427, a Novel AKT/PDK1 Inhibitor, for the Treatment of Head and Neck Squamous Cell Carcinoma. Pharmaceutics. 2021 Aug 12;13(8):1242. doi: 10.3390/pharmaceutics13081242. PMID: 34452203; PMCID: PMC8401941. 3. Meuillet EJ, Zuohe S, Lemos R, Ihle N, Kingston J, Watkins R, Moses SA, Zhang S, Du-Cuny L, Herbst R, Jacoby JJ, Zhou LL, Ahad AM, Mash EA, Kirkpatrick DL, Powis G. Molecular pharmacology and antitumor activity of PHT-427, a novel Akt/phosphatidylinositide-dependent protein kinase 1 pleckstrin homology domain inhibitor. Mol Cancer Ther. 2010 Mar;9(3):706-17. doi: 10.1158/1535-7163.MCT-09-0985. Epub 2010 Mar 2. PMID: 20197390; PMCID: PMC2837366.
In vitro protocol: 1. Li X, Wang Q, Zheng J, Guan Y, Liu C, Han J, Liu S, Liu T, Xiao C, Wang X, Liu Y. PHT427 as an effective New Delhi metallo-β-lactamase-1 (NDM-1) inhibitor restored the susceptibility of meropenem against Enterobacteriaceae producing NDM-1. Front Microbiol. 2023 Apr 17;14:1168052. doi: 10.3389/fmicb.2023.1168052. PMID: 37138606; PMCID: PMC10150926. 2. Yanes-Díaz J, Palao-Suay R, Aguilar MR, Riestra-Ayora JI, Ferruelo-Alonso A, Rojo Del Olmo L, Vázquez-Lasa B, Sanz-Fernández R, Sánchez-Rodríguez C. Antitumor Activity of Nanoparticles Loaded with PHT-427, a Novel AKT/PDK1 Inhibitor, for the Treatment of Head and Neck Squamous Cell Carcinoma. Pharmaceutics. 2021 Aug 12;13(8):1242. doi: 10.3390/pharmaceutics13081242. PMID: 34452203; PMCID: PMC8401941.
In vivo protocol: 1. Meuillet EJ, Zuohe S, Lemos R, Ihle N, Kingston J, Watkins R, Moses SA, Zhang S, Du-Cuny L, Herbst R, Jacoby JJ, Zhou LL, Ahad AM, Mash EA, Kirkpatrick DL, Powis G. Molecular pharmacology and antitumor activity of PHT-427, a novel Akt/phosphatidylinositide-dependent protein kinase 1 pleckstrin homology domain inhibitor. Mol Cancer Ther. 2010 Mar;9(3):706-17. doi: 10.1158/1535-7163.MCT-09-0985. Epub 2010 Mar 2. PMID: 20197390; PMCID: PMC2837366.

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1: Meuillet EJ, Zuohe S, Lemos R, Ihle N, Kingston J, Watkins R, Moses SA, Zhang  S, Du-Cuny L, Herbst R, Jacoby JJ, Zhou LL, Ahad AM, Mash EA, Kirkpatrick DL, Powis G. Molecular pharmacology and antitumor activity of PHT-427, a novel Akt/phosphatidylinositide-dependent protein kinase 1 pleckstrin homology domain inhibitor. Mol Cancer Ther. 2010 Mar;9(3):706-17. Epub 2010 Mar 2. PubMed PMID: 20197390; PubMed Central PMCID: PMC2837366.