PHT-427 | CAS#1191951-57-1 | AKT & PDPK1 inhibitor

MedKoo Cat#: 401705 | Name: PHT-427

Description:

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

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

PHT-427

CAS#1191951-57-1

Theoretical Analysis

MedKoo Cat#: 401705

Name: PHT-427

CAS#: 1191951-57-1

Chemical Formula: C20H31N3O2S2

Exact Mass: 409.1858

Molecular Weight: 409.61

Elemental Analysis: C, 58.64; H, 7.63; N, 10.26; O, 7.81; S, 15.66

Price and Availability

Size	Price	Availability
10mg	USD 150.00	2 Weeks
25mg	USD 250.00	2 Weeks
50mg	USD 450.00	2 Weeks
100mg	USD 800.00	2 Weeks

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Related CAS #

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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

View handling instruction

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/

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

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

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.

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:

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.

1: Yang M, Li L. Remimazolam attenuates inflammation in bronchopneumonia through the inhibition of NLRP3 activity by PDPK1 ubiquitination. Chem Biol Drug Des. 2024 Jan;103(1):e14438. doi: 10.1111/cbdd.14438. PMID: 38230783. 2: 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. 3: Fang J, Li R, Zhang Y, Oduro PK, Li S, Leng L, Wang Z, Rao Y, Niu L, Wu HH, Wang Q. Aristolone in Nardostachys jatamansi DC. induces mesenteric vasodilation and ameliorates hypertension via activation of the KATP channel and PDK1-Akt-eNOS pathway. Phytomedicine. 2022 Sep;104:154257. doi: 10.1016/j.phymed.2022.154257. Epub 2022 Jun 9. PMID: 35738117. 4: 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. 5: Shin M, Mun D, Choi HJ, Kim S, Payne SM, Kim Y. Identification of a New Antimicrobial Agent against Bovine Mastitis-Causing Staphylococcus aureus. J Agric Food Chem. 2021 Sep 1;69(34):9968-9978. doi: 10.1021/acs.jafc.1c02738. Epub 2021 Aug 18. PMID: 34406764. 6: Miller MS, Allen PJ, Brown PH, Chan AT, Clapper ML, Dashwood RH, Demehri S, Disis ML, DuBois RN, Glynn RJ, Kensler TW, Khan SA, Johnson BD, Liby KT, Lipkin SM, Mallery SR, Meuillet EJ, Roden RBS, Schoen RE, Sharp ZD, Shirwan H, Siegfried JM, Rao CV, You M, Vilar E, Szabo E, Mohammed A. Meeting Report: Translational Advances in Cancer Prevention Agent Development Meeting. J Cancer Prev. 2021 Mar 30;26(1):71-82. doi: 10.15430/JCP.2021.26.1.71. PMID: 33842408; PMCID: PMC8020174. 7: Uko NE, Güner OF, Matesic DF, Bowen JP. Akt Pathway Inhibitors. Curr Top Med Chem. 2020;20(10):883-900. doi: 10.2174/1568026620666200224101808. PMID: 32091335. 8: Yamaji M, Ota A, Wahiduzzaman M, Karnan S, Hyodo T, Konishi H, Tsuzuki S, Hosokawa Y, Haniuda M. Novel ATP-competitive Akt inhibitor afuresertib suppresses the proliferation of malignant pleural mesothelioma cells. Cancer Med. 2017 Nov;6(11):2646-2659. doi: 10.1002/cam4.1179. Epub 2017 Sep 27. PMID: 28960945; PMCID: PMC5673922. 9: Rickard RE, Young AMJ, Gerdjikov TV. Cortical Local Field Potential Power Is Associated with Behavioral Detection of Near-threshold Stimuli in the Rat Whisker System: Dissociation between Orbitofrontal and Somatosensory Cortices. J Cogn Neurosci. 2018 Jan;30(1):42-49. doi: 10.1162/jocn_a_01187. Epub 2017 Sep 11. PMID: 28891783. 10: Kobes JE, Daryaei I, Howison CM, Bontrager JG, Sirianni RW, Meuillet EJ, Pagel MD. Improved Treatment of Pancreatic Cancer With Drug Delivery Nanoparticles Loaded With a Novel AKT/PDK1 Inhibitor. Pancreas. 2016 Sep;45(8):1158-66. doi: 10.1097/MPA.0000000000000607. PMID: 26918875; PMCID: PMC4983222. 11: Dickinson SE, Janda J, Criswell J, Blohm-Mangone K, Olson ER, Liu Z, Barber C, Petricoin EF 3rd, Calvert VS, Einspahr J, Dickinson JE, Stratton SP, Curiel- Lewandrowski C, Saboda K, Hu C, Bode AM, Dong Z, Alberts DS, Timothy Bowden G. Inhibition of Akt Enhances the Chemopreventive Effects of Topical Rapamycin in Mouse Skin. Cancer Prev Res (Phila). 2016 Mar;9(3):215-24. doi: 10.1158/1940-6207.CAPR-15-0419. Epub 2016 Jan 22. PMID: 26801880; PMCID: PMC4777684. 12: Lucero-Acuña A, Guzmán R. Nanoparticle encapsulation and controlled release of a hydrophobic kinase inhibitor: Three stage mathematical modeling and parametric analysis. Int J Pharm. 2015 Oct 15;494(1):249-57. doi: 10.1016/j.ijpharm.2015.07.049. Epub 2015 Jul 26. PMID: 26216413. 13: Li A, Wang J, Wu M, Zhang X, Zhang H. The inhibition of activated hepatic stellate cells proliferation by arctigenin through G0/G1 phase cell cycle arrest: persistent p27(Kip1) induction by interfering with PI3K/Akt/FOXO3a signaling pathway. Eur J Pharmacol. 2015 Jan 15;747:71-87. doi: 10.1016/j.ejphar.2014.11.040. Epub 2014 Dec 10. PMID: 25498792. 14: 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. 15: Moses SA, Ali MA, Zuohe S, Du-Cuny L, Zhou LL, Lemos R, Ihle N, Skillman AG, Zhang S, Mash EA, Powis G, Meuillet EJ. In vitro and in vivo activity of novel small-molecule inhibitors targeting the pleckstrin homology domain of protein kinase B/AKT. Cancer Res. 2009 Jun 15;69(12):5073-81. doi: 10.1158/0008-5472.CAN-08-3839. Epub 2009 Jun 2. PMID: 19491272; PMCID: PMC2914301.