Synonyms: LB100
Compound class:
Synthetic organic
Comment: LB-100 is a small molecule inhibitor of protein phosphatase 2A (PP2A) [3]. PP2A is a pivotal cellular switch that controls important events that impinge on cellular survival and death, such as cell cycle, apoptosis, and autophagy. PP2A acts on kinase substrates in a number of critical signal transduction pathways (including MAPK, Wnt, PI3K, NF&kappB, PKC, and Ca2+/calmodulin-dependent signalling pathways). PP2A is a validated oncology target. Studies have shown that LB-100 has anti-tumour activity [2] and can sensitise pancreatic cancer to chemotherapy [1] and radiotherapy [3].
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References |
1. Bai X, Zhi X, Zhang Q, Liang F, Chen W, Liang C, Hu Q, Sun X, Zhuang Z, Liang T. (2014)
Inhibition of protein phosphatase 2A sensitizes pancreatic cancer to chemotherapy by increasing drug perfusion via HIF-1α-VEGF mediated angiogenesis. Cancer Lett, 355 (2): 281-7. [PMID:25304380] |
2. Ho WS, Wang H, Maggio D, Kovach JS, Zhang Q, Song Q, Marincola FM, Heiss JD, Gilbert MR, Lu R et al.. (2018)
Pharmacologic inhibition of protein phosphatase-2A achieves durable immune-mediated antitumor activity when combined with PD-1 blockade. Nat Commun, 9 (1): 2126. [PMID:29844427] |
3. Wei D, Parsels LA, Karnak D, Davis MA, Parsels JD, Marsh AC, Zhao L, Maybaum J, Lawrence TS, Sun Y et al.. (2013)
Inhibition of protein phosphatase 2A radiosensitizes pancreatic cancers by modulating CDC25C/CDK1 and homologous recombination repair. Clin Cancer Res, 19 (16): 4422-32. [PMID:23780887] |