The Patent Landscape of mTOR and PTEN Targets


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Abstract

Background:PTEN and mTOR signaling have many roles, including antiinflammatory, immunosuppressant and cancer.

Objective:US patents were retrieved to show the current landscape of the mTOR and PTEN targets.

Methods:PTEN and mTOR targets were analyzed by patent analysis. The U.S. granted patents from January 2003 to July 2022 were performed and analyzed.

Results:The results showed that the mTOR target was more attractive in drug discovery than the PTEN target. Our findings indicated that most large global pharmaceutical companies focused the drug discovery related to the mTOR target. The present study demonstrated that mTOR and PTEN targets showed more applications in biological approaches compared to BRAF and KRAS targets. The chemical structures of the inhibitors of the mTOR target demonstrated some similar features to those of the inhibitors of KRAS targets.

Conclusion:At this stage, the PTEN target may not be an ideal target subjected to new drug discovery. The present study was the first one which demonstrated that the group of O=S=O may play a critical role in the chemical structures of mTOR inhibitors. It was the first time to show that a PTEN target may be suitably subjected to new therapeutic discovery efforts related to biological applications. Our findings provide a recent insight into therapeutic development for mTOR and PTEN targets.

About the authors

Hai-long Zhang

, Central International Intellectual Property (Baotou) Co., Ltd.

Author for correspondence.
Email: info@benthamscience.net

Yongxia Li

, Central International Intellectual Property (Baotou) Co., Ltd.

Email: info@benthamscience.net

References

  1. Song X, Tan L, Wang M, et al. Myricetin: A review of the most recent research. Biomed Pharmacother 2021; 134: 111017. doi: 10.1016/j.biopha.2020.111017 PMID: 33338751
  2. Tsang CK, Qi H, Liu LF, Zheng XFS. Targeting mammalian target of rapamycin (mTOR) for health and diseases. Drug Discov Today 2007; 12(3-4): 112-24. doi: 10.1016/j.drudis.2006.12.008 PMID: 17275731
  3. Grabiner BC, Nardi V, Birsoy K, et al. A diverse array of cancer-associated MTOR mutations are hyperactivating and can predict rapamycin sensitivity. Cancer Discov 2014; 4(5): 554-63. doi: 10.1158/2159-8290.CD-13-0929 PMID: 24631838
  4. Ghosh AP, Marshall CB, Coric T, et al. Point mutations of the mTOR-RHEB pathway in renal cell carcinoma. Oncotarget 2015; 6(20): 17895-910. doi: 10.18632/oncotarget.4963 PMID: 26255626
  5. Drakos E, Atsaves V, Li J, et al. Stabilization and activation of p53 downregulates mTOR signaling through AMPK in mantle cell lymphoma. Leukemia 2009; 23(4): 784-90. doi: 10.1038/leu.2008.348 PMID: 19225536
  6. Feng Z, Zhang H, Levine AJ, Jin S. The coordinate regulation of the p53 and mTOR pathways in cells. Proc Natl Acad Sci 2005; 102(23): 8204-9. doi: 10.1073/pnas.0502857102 PMID: 15928081
  7. Mendoza MC, Er EE, Blenis J. The Ras-ERK and PI3K-mTOR pathways: Cross-talk and compensation. Trends Biochem Sci 2011; 36(6): 320-8. doi: 10.1016/j.tibs.2011.03.006 PMID: 21531565
  8. de Oliveira SFL, Carletti VJ, Azevedo FFN, et al. mTOR–mLST8 interaction: Hot spot identification through quantum biochemistry calculations. New J Chem 2020; 44(48): 20982-92. doi: 10.1039/D0NJ04099A
  9. LaSarge CL, Pun RYK, Gu Z, Santos VR, Danzer SC. Impact of mTOR hyperactive neurons on the morphology and physiology of adjacent neurons: Do PTEN KO cells make bad neighbors? Exp Neurol 2019; 321: 113029. doi: 10.1016/j.expneurol.2019.113029 PMID: 31377403
  10. Yang F, Yang L, Wataya-Kaneda M, Teng L, Katayama I. Epilepsy in a melanocyte-lineage mTOR hyperactivation mouse model: A novel epilepsy model. PLoS One 2020; 15(1): e0228204. doi: 10.1371/journal.pone.0228204 PMID: 31978189
  11. Stambolic V, Suzuki A, de la Pompa JL, et al. Negative regulation of PKB/Akt-dependent cell survival by the tumor suppressor PTEN. Cell 1998; 95(1): 29-39. doi: 10.1016/S0092-8674(00)81780-8 PMID: 9778245
  12. Wang Y, Romigh T, He X, et al. Resveratrol regulates the PTEN/AKT pathway through androgen receptor-dependent and -independent mechanisms in prostate cancer cell lines. Hum Mol Genet 2010; 19(22): 4319-29. doi: 10.1093/hmg/ddq354 PMID: 20729295
  13. Broderick DK, Di C, Parrett TJ, et al. Mutations of PIK3CA in anaplastic oligodendrogliomas, high-grade astrocytomas, and medulloblastomas. Cancer Res 2004; 64(15): 5048-50. doi: 10.1158/0008-5472.CAN-04-1170 PMID: 15289301
  14. Stewart AL, Mhashilkar AM, Yang XH, et al. PI3K blockade by Ad-PTEN inhibits invasion and induces apoptosis in radial growth phase and metastatic melanoma cells. Mol Med 2002; 8(8): 451-61. doi: 10.1007/BF03402025
  15. Dong JT, Li CL, Sipe TW, Frierson HF Jr. Mutations of PTEN/MMAC1 in primary prostate cancers from Chinese patients. Clin Cancer Res 2001; 7(2): 304-8. PMID: 11234884
  16. Boosani CS, Agrawal DK. PTEN modulators: A patent review. Expert Opin Ther Pat 2013; 23(5): 569-80. doi: 10.1517/13543776.2013.768985 PMID: 23379765
  17. Mak LH, Woscholski R. Targeting PTEN using small molecule inhibitors. Methods 2015; 77-78: 63-8. doi: 10.1016/j.ymeth.2015.02.007 PMID: 25747336
  18. Davé V, Wert SE, Tanner T, Thitoff AR, Loudy DE, Whitsett JA. Conditional deletion of Pten causes bronchiolar hyperplasia. Am J Respir Cell Mol Biol 2008; 38(3): 337-45. doi: 10.1165/rcmb.2007-0182OC PMID: 17921358
  19. The U.S. Food and Drug Administration Available from: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2007/022088s000_PRNTLBL.pdf
  20. The U.S. Food and Drug Administration Available from:https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/213312lbl.pdf
  21. Gray NS, Waller D, Choi HG, Wang J. Pyrimido-diazepinone compounds and methods of treating disorders Patent US10457692B2,, 2019.
  22. LUO J. Fusion genes associated with progressive prostate cancer. Patent US10167519B2, 2019.
  23. Sabatini DM. mTOR kinase-associated proteins Patent US8258271B2, 2012.
  24. Zheng S. MTOR kinase mutations and methods of use thereof . Patent US10551384B2, 2020.
  25. Choi JW. Nucleic acid simultaneously inhibiting expression of mTOR gene and STAT3 gene Patent US11149272B2, , 2021.
  26. Park JY. Analytical method for increasing susceptibility of molecular targeted therapy in hepatocellular carcinoma Patent US10017823B2, 2018.
  27. Ren P. Benzoxazole kinase inhibitors and methods of use Patent US8476431B2, 2013.
  28. Nagaraj HK. Pyrimidine substituted purine derivatives Patent US8609838B2,, 2013.
  29. Ren P. Kinase inhibitors and methods of use Patent US9096611B2, 2015.
  30. Fernandez JP. Macrocyclic compounds as protein kinase inhibitors Patent US9284334B2, 2016.
  31. Lynch R. Morpholino substituted urea derivatives as mTOR inhibitors. Patent 2016.
  32. Lynch R. Morpholino substituted bicyclic pyrimidine urea or carbamate derivatives as mTOR inhibitors Patent US9242993B2, 2016.
  33. Guan H. Pyridino1,2-Apyrimidone analogue used as MTOR/P13K inhibitor Patent US9868737B2, 2018.
  34. Mitra AK. Ophthalmic compositions Patent US10973871B2, , 2021.
  35. Kaupinen WH. Anhydrous compositions of mTOR inhibitors and methods of use . Patent US11000513B2, , 2021.
  36. Mitra AK. Ophthalmic compositions comprising calcineurin inhibitors or mTOR inhibitors . Patent US8435544B2, 2013.
  37. Kaupinen WH. Anhydrous compositions of mTOR inhibitors and methods of use . Patent US11135204B2, , 2021.
  38. Jones D. Method and compositions for detecting an adenoma-adenocarcinoma transition in cancer Patent US10890587B2, 2021.
  39. YU JS Systems and methods for prognosticating brain tumors Patent US9915659B2, 2018.
  40. Pestano G. Expression of ETS related gene (ERG) and phosphatase and tensin homolog (PTEN) correlates with prostate cancer capsular penetration Patent US10407736B2, 2019.
  41. Pandolfi PP. . micro-RNA inhibitors and their uses in disease. Patent US11274301B2,, 2022.
  42. Pandolfi PP. Micro-RNA inhibitors and their uses in disease Patent US10131905B2, 2018.
  43. Costa MR. Marks as modifers of the PTEN pathway and methods of use Patent US8273536B2,, 2012.
  44. Cunningham K. Peptide inhibitors of serotonin 5- HT2c receptors: PTEN interaction. Patent US9611292B2, 2017.
  45. Chang CH. Multiple signaling pathways induced by hexavalent, monospecific and bispecific antibodies for enhanced toxicity to B-cell lymphomas and other diseases Patent US8349332B2, 2013.
  46. Hoek VT. Peptides and method for treatment of cardiac arrest Patent US10688153B2, 2020.
  47. Guy RK. Small molecule inhibition of a PDZ-domain interaction. Patent US7601750B2, 2009.
  48. Caponigro G. Combination therapy Patent US10548894B2,, 2020.
  49. Durden L. . Compositions and methods for identifying agents which modulate PTEN function and PI-3 kinase pathways. Patent US8163691B2, 2012.
  50. Thompson SK. Quinazolines and azaquinazolines as dual inhibitors of RAS/RAF/MEK/ERK and PI3K/AKT/PTEN/mTOR pathways. Patent US9757382B2, 2017.
  51. Thompson SK. Quinazolines and azaquinazolines as dual inhibitors of RAS/RAF/MEK/ERK and PI3K/AKT/PTEN/mTOR pathways. Patent US9499495B2, 2016.
  52. Hong KW. PTEN inhibitor or Maxi-K channels opener Patent US8329731B2, 2012.
  53. Vali S. Combination of nelfinavir, metformin and rosuvastatin for treating cancer caused by aberrations in PTEN/TP53 Patent US10098880B2,, 2018.
  54. Zhang H-L, Li Y. The patent landscape of BRAF target and KRAS target. Recent Pat Anticancer Drug Discov 2023; 18: 495-505.
  55. Zhang H-L, Li Y-X, Zhou A-F, Li Y. New frontier in drugs for antivirals in disorders of the respiratory system. Recent Adv Anti-Infective Drug Discov 2022; p. 17.
  56. Zhang HL, Li Y. Recent development of drugs for osteoporosis and anti-cancer agents: A patent analysis. Pharm Pat Anal 202(10): 73-82.
  57. Zhang H-L, Zhou A-F, Li Y. Patent Insight into the development of therapeutic strategies against coronaviruses. Open COVID J 2021; 1: 93-100.
  58. Li J, Zhou Q, Liang Y, et al. miR-486 inhibits PM2.5-induced apoptosis and oxidative stress in human lung alveolar epithelial A549 cells. Ann Transl Med 2018; 6(11): 209. doi: 10.21037/atm.2018.06.09 PMID: 30023372
  59. Quan Y, Wang Z, Gong L, et al. Exosome miR-371b-5p promotes proliferation of lung alveolar progenitor type II cells by using PTEN to orchestrate the PI3K/Akt signaling. Stem Cell Res Ther 2017; 8(1): 138. doi: 10.1186/s13287-017-0586-2 PMID: 28595637
  60. Chauhan A, Sah DK, Kumari N, Kalra N, Soni R, Bhatt AN. PTEN inhibitor bpV(HOpic) confers protection against ionizing radiation. Sci Rep 2021; 11(1): 1720. doi: 10.1038/s41598-020-80754-8 PMID: 33462262

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