An LC–MS/MS method for simultaneous determination of LB-100 and its active metabolite, endothall, in human plasma

Papers of special note have been highlighted as: • of interest; •• of considerable interest

References

• 1. Perrotti D, Neviani P. Protein phosphatase 2A: a target for anticancer therapy. Lancet Oncol. 14(6), e229–238 (2013).
  Medline CASGoogle Scholar
• 2. Hong CS, Ho W, Zhang C, Yang C, Elder JB, Zhuang Z. LB100, a small molecule inhibitor of PP2A with potent chemo- and radio-sensitizing potential. Cancer Biol. Ther. 16(6), 821–833 (2015). • Review of LB-100 as a novel protein phosphatase 2A inhibitor with a tremendous therapeutic potential in a variety of cancer types.
  Medline CASGoogle Scholar
• 3. Maggio D, Ho WS, Breese R et al. Inhibition of protein phosphatase-2A with LB-100 enhances antitumor immunity against glioblastoma. J. Neurooncol. 148(2), 231–244 (2020).
  Medline CASGoogle Scholar
• 4. Cui J, Wang H, Medina R et al. Inhibition of PP2A with LB-100 enhances efficacy of CAR-T cell therapy against glioblastoma. Cancers 12(1), 139 (2020).
  Medline CASGoogle Scholar
• 5. D'Arcy BM, Swingle MR, Papke CM et al. The antitumor drug LB-100 is a catalytic inhibitor of protein phosphatase 2A (PPP2CA) and 5 (PPP5C) coordinating with the active-site catalytic metals in PPP5C. Mol. Cancer Ther. 18(3), 556–566 (2019).
  MedlineGoogle Scholar
• 6. Ronk H, Rosenblum JS, Kung T, Zhuang Z. Targeting PP2A for cancer therapeutic modulation. Cancer Biol. Med. 19(10), 1428–1439 (2022). • Description of the background and preclinical/clinical results of LB-100 as a chemo- and radio-sensitizing agent.
  MedlineGoogle Scholar
• 7. Hao S, Song H, Zhang W et al. Protein phosphatase 2A inhibition enhances radiation sensitivity and reduces tumor growth in chordoma. Neuro Oncol. 20(6), 799–809 (2018).
  Medline CASGoogle Scholar
• 8. Uddin MH, Pimentel JM, Chatterjee M, Allen JE, Zhuang Z, Wu GS. Targeting PP2A inhibits the growth of triple-negative breast cancer cells. Cell Cycle 19(5), 592–600 (2020).
  Medline CASGoogle Scholar
• 9. Ho WS, Sizdahkhani S, Hao S et al. LB-100, a novel protein phosphatase 2A (PP2A) inhibitor, sensitizes malignant meningioma cells to the therapeutic effects of radiation. Cancer Lett. 415, 217–226 (2018).
  Medline CASGoogle Scholar
• 10. Lai D, Chen M, Su J et al. PP2A inhibition sensitizes cancer stem cells to ABL tyrosine kinase inhibitors in BCR-ABL⁺ human leukemia. Sci. Transl. Med. 10(427), eaan8735 (2018).
  MedlineGoogle Scholar
• 11. Yen Y-T, Chien M, Wu P-Y et al. Protein phosphatase 2A inactivation induces microsatellite instability, neoantigen production and immune response. Nat. Commun. 12, 7297 (2021).
  Medline CASGoogle Scholar
• 12. Song Q, Wang H, Jiang D et al. Pharmacological inhibition of PP2A overcomes Nab-paclitaxel resistance by downregulating MCL1 in esophageal squamous cell carcinoma (ESCC). Cancers 13(19), 4766 (2021).
  Medline CASGoogle Scholar
• 13. Mirzapoiazova T, Xiao G, Mambetsariev B et al. Protein phosphatase 2A as a therapeutic target in small cell lung cancer. Mol. Cancer Ther. 20(10), 1820–1835 (2021).
  Medline CASGoogle Scholar
• 14. Chung V, Mansfield AS, Braiteh F et al. Safety, tolerability, and preliminary activity of LB-100, an inhibitor of protein phosphatase 2A, in patients with relapsed solid tumors: an open-label, dose escalation, first-in-human, phase I trial. Clin. Cancer Res. 23(13), 3277–3284 (2017). •• The safety, tolerability and preliminary evidence of antitumor activity of LB-100 supported its continued development alone and in combination with other therapies.
  Medline CASGoogle Scholar
• 15. D’Arcy BM, Prakash A, Honkanen RE. Targeting phosphatases in cancer: suppression of many versus the ablation of one. Oncotarget 10(61), 6543–6545 (2019).
  MedlineGoogle Scholar
• 16. Kovach JS, Volkmann R, Marfat A: US20160333024A1 (2016). •• The LB-100 patent from Lixte Biotechnology with the background of drug designing and an LC–MS assay of drug determination.
  Google Scholar
• 17. City of Hope Medical Center. A phase Ib open-label study of LB-100 in combination with carboplatin/etoposide/atezolizumab in untreated extensive-stage small cell lung carcinoma. https://clinicaltrials.gov/ct2/show/NCT04560972
  Google Scholar
• 18. Quang C, Simko JL, Nethero WC, Groeber EA, Kovach JS. LC–MS/MS method development and validation for the quantification of LB-100 and endothall metabolite in biological matrices. In: Proceedings of the 64th Conference on Mass Spectrometry and Allied Topics. American Society for Mass Spectrometry, TX, USA; NM, USA (2016). Poster MP 158.
  Google Scholar
• 19. Sikka HC, Rice CP. Persistence of endothall in aquatic environment as determined by gas-liquid chromatography. J. Agric. Food Chem. 21(5), 842–846 (1973).
  Medline CASGoogle Scholar
• 20. Islam MS, Hunt TD, Liu Z, Butler KL, Dugdale TM. Sediment facilitates microbial degradation of the herbicides endothall monoamine salt and endothall dipotassium salt in an aquatic environment. Int. J. Environ. Res. Public Health 15(10), 2255 (2018).
  Medline CASGoogle Scholar
• 21. Wang L, Dionex Corporation, Schnute W. Direct determination of endothall in water samples by IC–MS (2011). www.chromatographyonline.com/view/direct-determination-endothall-water-samples-icms-0
  Google Scholar
• 22. Guo S, Mei S, Wang Q et al. Determination of cantharidic acid in rat blood by microdialysis combined with UHPLC–MS/MS. Int. J. Mass Spectrom. 440, 20–26 (2019). •• An LC–MS method using endothall as the internal standard.
  CASGoogle Scholar
• 23. US FDA. Guidance for Industry: Bioanalytical Method Validation. US Department of Health and Human Services, FDA, Center for Drug Evaluation And Research MD, USA (2018). www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinformation/guidances/ucm070107.pdf
  Google Scholar