For research use only. Not for therapeutic Use.
GSK461364（Cat No.:I005526）is a selective inhibitor of the enzyme PDK1 (3-phosphoinositide-dependent protein kinase-1), a key regulator in the PI3K/Akt signaling pathway. PDK1 is involved in various cellular processes such as cell survival, growth, and metabolism, and its dysregulation is often implicated in cancer. By inhibiting PDK1, GSK461364 aims to block oncogenic signaling pathways, potentially reducing tumor cell proliferation and enhancing the effectiveness of other cancer therapies. It has shown promise in preclinical studies for targeting various cancers, including solid tumors and hematological malignancies.
| Catalog Number | I005526 |
| CAS Number | 929095-18-1 |
| Synonyms | GSK-461364 |
| Molecular Formula | C₂₇H₂₈F₃N₅O₂S |
| Purity | ≥95% |
| Target | Polo-like Kinase (PLK) |
| Solubility | DMSO ≥9mg/mL Water <1.2mg/mL Ethanol ≥60mg/mL |
| Storage | 3 years -20C powder |
| IC50 | 2.2 nM(Ki) |
| IUPAC Name | 5-[6-[(4-methylpiperazin-1-yl)methyl]benzimidazol-1-yl]-3-[(1R)-1-[2-(trifluoromethyl)phenyl]ethoxy]thiophene-2-carboxamide |
| InChI | InChI=1S/C27H28F3N5O2S/c1-17(19-5-3-4-6-20(19)27(28,29)30)37-23-14-24(38-25(23)26(31)36)35-16-32-21-8-7-18(13-22(21)35)15-34-11-9-33(2)10-12-34/h3-8,13-14,16-17H,9-12,15H2,1-2H3,(H2,31,36)/t17-/m1/s1 |
| InChIKey | ZHJGWYRLJUCMRT-QGZVFWFLSA-N |
| SMILES | C[C@H](C1=CC=CC=C1C(F)(F)F)OC2=C(SC(=C2)N3C=NC4=C3C=C(C=C4)CN5CCN(CC5)C)C(=O)N |
| Reference | </br>1:The GSK461364 PLK1 inhibitor exhibits strong antitumoral activity in preclinical neuroblastoma models. Pajtler KW, Sadowski N, Ackermann S, Althoff K, Schönbeck K, Batzke K, Schäfers S, Odersky A, Heukamp L, Astrahantseff K, Künkele A, Deubzer HE, Schramm A, Sprüssel A, Thor T, Lindner S, Eggert A, Fischer M, Schulte JH.Oncotarget. 2017 Jan 24;8(4):6730-6741. doi: 10.18632/oncotarget.14268. PMID: 28036269 Free PMC Article</br>2:Cytotoxic mechanism of PLK1 inhibitor GSK461364 against osteosarcoma: Mitotic arrest, apoptosis, cellular senescence, and synergistic effect with paclitaxel. Chou YS, Yen CC, Chen WM, Lin YC, Wen YS, Ke WT, Wang JY, Liu CY, Yang MH, Chen TH, Liu CL.Int J Oncol. 2016 Mar;48(3):1187-94. doi: 10.3892/ijo.2016.3352. Epub 2016 Jan 20. PMID: 26794530 </br>3:Overexpression of human ABCB1 in cancer cells leads to reduced activity of GSK461364, a specific inhibitor of polo-like kinase 1. Wu CP, Hsiao SH, Luo SY, Tuo WC, Su CY, Li YQ, Huang YH, Hsieh CH.Mol Pharm. 2014 Oct 6;11(10):3727-36. doi: 10.1021/mp500492r. Epub 2014 Sep 18. PMID: 25192198 </br>4:BI 6727 and GSK461364 suppress growth and radiosensitize osteosarcoma cells, but show limited cytotoxic effects when combined with conventional treatments. Bogado RF, Pezuk JA, de Oliveira HF, Tone LG, Brassesco MS.Anticancer Drugs. 2015 Jan;26(1):56-63. doi: 10.1097/CAD.0000000000000157. PMID: 25089571 </br>5:Phase I study of GSK461364, a specific and competitive Polo-like kinase 1 inhibitor, in patients with advanced solid malignancies. Olmos D, Barker D, Sharma R, Brunetto AT, Yap TA, Taegtmeyer AB, Barriuso J, Medani H, Degenhardt YY, Allred AJ, Smith DA, Murray SC, Lampkin TA, Dar MM, Wilson R, de Bono JS, Blagden SP.Clin Cancer Res. 2011 May 15;17(10):3420-30. doi: 10.1158/1078-0432.CCR-10-2946. Epub 2011 Apr 1. PMID: 21459796 Free Article |
