1227911-45-6 Usage
Uses
Used in Pharmaceutical Industry:
GSK 2334470 is used as an inhibitor of 3-phosphoinositide dependent protein kinase-1 (PDK-1) for various applications, including:
1. Treg cells: To identify regulators of interleukin 2 (IL-2) – signal transducer and activator of transcription 5 (STAT5) signaling.
2. Glycodelin-transfected HEC-1B human endometrial adenocarcinoma cells: To study its effects on specific cellular processes.
3. HeLa and Hs578T cells: To test its effect on formylglycinamidine ribonucleotide synthase (FGAMS) assembly.
Additionally, GSK 2334470 has potential applications in cancer research and treatment, as it has demonstrated antitumor activity against multiple myeloma when used in combination with other inhibitors.
Biochem/physiol Actions
GSK2334470 (GSK-470) mediates cell cycle arrest. It also inhibits cellular proliferation and induces apoptosis in cancer cells.
References
1) Najafov?et al.?(2011), Characterization of GSK2334470, a novel and highly specific inhibitor of PDK1; Biochem.J.?433?37
2) Scortegagna?et al.?(2014), Genetic inactivation or pharmacological inhibition of Pdk1 delays development and inhibits metastasis of Braf (V600E)::Pten(-/-) melanoma; Oncogene?33?4330
3) Yang?et al.?(2017),PDK1 inhibitor GSK2334470 exerts antitumor activity in multiple myeloma and forms a novel multitargeted combination with dual mTORC1/C2 inhibitor PP242; Oncotarget?8?39185
4) Zhang?et al.?(2018), PDK1 inhibitor GSK2334470 synergizes with proteasome inhibitor MG-132 in multiple myeloma cells by inhibiting full AKT activity and increasing nuclear accumulation of PTEN protein; Oncol.Rep.?39 2951
Check Digit Verification of cas no
The CAS Registry Mumber 1227911-45-6 includes 10 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 7 digits, 1,2,2,7,9,1 and 1 respectively; the second part has 2 digits, 4 and 5 respectively.
Calculate Digit Verification of CAS Registry Number 1227911-45:
(9*1)+(8*2)+(7*2)+(6*7)+(5*9)+(4*1)+(3*1)+(2*4)+(1*5)=146
146 % 10 = 6
So 1227911-45-6 is a valid CAS Registry Number.
1227911-45-6Relevant articles and documents
Structure-based design of potent and selective 3-phosphoinositide-dependent kinase-1 (PDK1) inhibitors
Medina, Jesús R.,Becker, Christopher J.,Blackledge, Charles W.,Duquenne, Celine,Feng, Yanhong,Grant, Seth W.,Heerding, Dirk,Li, William H.,Miller, William H.,Romeril, Stuart P.,Scherzer, Daryl,Shu, Arthur,Bobko, Mark A.,Chadderton, Antony R.,Dumble, Melissa,Gardiner, Christine M.,Gilbert, Seth,Liu, Qi,Rabindran, Sridhar K.,Sudakin, Valery,Xiang, Hong,Brady, Pat G.,Campobasso, Nino,Ward, Paris,Axten, Jeffrey M.
scheme or table, p. 1871 - 1895 (2011/05/30)
Phosphoinositide-dependent protein kinase-1(PDK1) is a master regulator of the AGC family of kinases and an integral component of the PI3K/AKT/mTOR pathway. As this pathway is among the most commonly deregulated across all cancers, a selective inhibitor of PDK1 might have utility as an anticancer agent. Herein we describe our lead optimization of compound 1 toward highly potent and selective PDK1 inhibitors via a structure-based design strategy. The most potent and selective inhibitors demonstrated submicromolar activity as measured by inhibition of phosphorylation of PDK1 substrates as well as antiproliferative activity against a subset of AML cell lines. In addition, reduction of phosphorylation of PDK1 substrates was demonstrated in vivo in mice bearing OCl-AML2 xenografts. These observations demonstrate the utility of these molecules as tools to further delineate the biology of PDK1 and the potential pharmacological uses of a PDK1 inhibitor.
