1191951-57-1 Usage
Description
PHT-427 is a dual Akt and PDPK1 inhibitor, characterized by its Ki values of 2.7 μM and 5.2 μM, respectively. It is a pleckstrin homology domain inhibitor that targets Akt and PKB Kinase (PDPK1), playing a significant role in various cellular processes and diseases.
Uses
Used in Pharmaceutical Applications:
PHT-427 is used as a dual Akt and PDPK1 inhibitor for its potential therapeutic effects in treating diseases associated with the dysregulation of these kinases. Its ability to inhibit both Akt and PDPK1 makes it a valuable compound for research and drug development.
Used in Biological Research:
PHT-427 is used as a pleckstrin homology domain inhibitor to study the roles of Akt and PDPK1 in cellular signaling pathways. This helps researchers understand the molecular mechanisms underlying various diseases and develop targeted therapies.
Used in Mathematical Modeling and Parametric Analysis:
PHT-427 is used for the study of mathematical modeling and parametric analysis of nanoparticle encapsulation and controlled release. This application aids in the development of efficient drug delivery systems for hydrophobic kinase inhibitors like PHT-427, enhancing their bioavailability and therapeutic outcomes.
Biological Activity
pht-427 is an inhibitor of akt and pdpk1 (ki =2.7 μm and 5.2 μm, respectively).akt is a serine/threonine-specific protein kinase that plays a vital role in multiple cellular processes including glucose metabolism, apoptosis, cell proliferation, transcription and cell migration etc.in bxpc-3 cells, pht-427 showed inhibition upon akt function with ic50 value of 8.6±0.8 μm and for its downstream substrates. pht-427 reduced the akt phosphorylation on ser473 residue and did not decrease total akt protein level. pht-427 also inhibited p70s6k and gsk3β in a dose-dependent manner. [1][2]in scid (severe combined immunodeficiency) mice of bxpc-3 pancreatic cancer xenografts, administration of pht-427 exerted prominent antitumor activity that halted tumor growth. pht-427 in combination with erlotinib exhibited greater than additive antitumor activity in nsc lung cancer and with paclitaxel in breast cancer. [1][2]
Enzyme inhibitor
This orally bioavailable, dual Akt/PDPK1 inhibitor (F.Wt. = 409.61; CAS 1191951-57-1 and 1178893-77-0; Solubility (25°C): 80 mg/mL DMSO, <1 mg/mL Water), known systematically as 4-dodecyl-N-(1,3,4-thiadiazol-2- yl)benzenesulfonamide, targets Akt (also known as Protein Kinase B, or PKB) and 3-phosphoinositide-dependent protein kinase-1, with Ki of 2.7 μM and 5.2 μM, respectively. PHT-427 was designed to bind to the pleckstrin homology (PH) auto-inhibitory domains of the signal cascade protein kinase Akt.
references
1. meuillet ej, zuohe s, lemos r et al. 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):706-17.2. moses sa, ali ma, zuohe s et al. 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.
Check Digit Verification of cas no
The CAS Registry Mumber 1191951-57-1 includes 10 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 7 digits, 1,1,9,1,9,5 and 1 respectively; the second part has 2 digits, 5 and 7 respectively.
Calculate Digit Verification of CAS Registry Number 1191951-57:
(9*1)+(8*1)+(7*9)+(6*1)+(5*9)+(4*5)+(3*1)+(2*5)+(1*7)=171
171 % 10 = 1
So 1191951-57-1 is a valid CAS Registry Number.
1191951-57-1Relevant articles and documents
Development of sulfonamide AKT PH domain inhibitors
Ahad, Ali Md.,Zuohe, Song,Du-Cuny, Lei,Moses, Sylvestor A.,Zhou, Li Li,Zhang, Shuxing,Powis, Garth,Meuillet, Emmanuelle J.,Mash, Eugene A.
scheme or table, p. 2046 - 2054 (2011/05/05)
Disruption of the phosphatidylinositol 3-kinase/AKT signaling pathway can lead to apoptosis in cancer cells. Previously we identified a lead sulfonamide that selectively bound to the pleckstrin homology (PH) domain of AKT and induced apoptosis when present at low micromolar concentrations. To examine the effects of structural modification, a set of sulfonamides related to the lead compound was designed, synthesized, and tested for binding to the expressed PH domain of AKT using a surface plasmon resonance-based competitive binding assay. Cellular activity was determined by means of an assay for pAKT production and a cell killing assay using BxPC-3 cells. The most active compounds in the set are lipophilic and possess an aliphatic chain of the proper length. Results were interpreted with the aid of computational modeling. This paper represents the first structure-activity relationship (SAR) study of a large family of AKT PH domain inhibitors. Information obtained will be used in the design of the next generation of inhibitors of AKT PH domain function.
