PTEN modulators: A patent review

Expert Opinion on Therapeutic Patents

Volumn 23, Issue 5, 2013, Pages 569-580

  Boosani, Chandra S ^a   Agrawal, Devendra K ^a  

^a CREIGHTON UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

Cancer; Cardiovascular diseases; Kinases; Modulators; Obesity; Phosphatase; PTEN; Transcription factors

Indexed keywords

4,5,6,7 TETRABROMO 2 DIMETHYLAMINO 1H BENZIMIDAZOLE; CELL PROTEIN; CETUXIMAB; CT 99021; ERLOTINIB; GAMMA SECRETASE INHIBITOR; GEFITINIB; GLYCOGEN SYNTHASE KINASE 3 INHIBITOR; HERBIMYCIN; MEVINOLIN; NVP AEW 541; PERTUZUMAB; PHOSPHATIDYLINOSITOL 3,4,5 TRISPHOSPHATE 3 PHOSPHATASE; RESISTIN; RITUXIMAB; ROSIGLITAZONE; SALINOSPORAMIDE A; SIMVASTATIN; SODIUM SELENITE; SUNITINIB; TRANSCRIPTION FACTOR; TRASTUZUMAB; UBLITUXIMAB; UNCLASSIFIED DRUG;

AUTISM; DRUG MECHANISM; DRUG TARGETING; ENZYME ACTIVITY; ENZYME INHIBITION; GENE MUTATION; HEART FAILURE; HUMAN; NON INSULIN DEPENDENT DIABETES MELLITUS; NONHUMAN; OBESITY; PROTEIN EXPRESSION; PROTEIN FUNCTION; PROTEIN MODIFICATION; PROTEIN PHOSPHORYLATION; PROTEIN PROCESSING; PROTEIN PROTEIN INTERACTION; PROTEIN STRUCTURE; REVIEW; SIGNAL TRANSDUCTION;

ANIMALS; DRUG DESIGN; HUMANS; MOLECULAR TARGETED THERAPY; PATENTS AS TOPIC; PHOSPHORYLATION; PHOSPHOTRANSFERASES; PTEN PHOSPHOHYDROLASE;

EID: 84876525535     PISSN: 13543776     EISSN: 17447674     Source Type: Journal    
DOI: 10.1517/13543776.2013.768985     Document Type: Review

References (96)

1. Wiencke JK, Zheng S, Jelluma N, et al. Methylation of the PTEN promoter defines low-grade gliomas and secondary glioblastoma. Neurol Oncol 2007;9(3):271-9 (Pubitemid 47169659)
2. Tamguney T, Stokoe D. New insights into PTEN. J Cell Sci 2007;120(Pt 23):4071-9
3. COSMIC: catalog of somatic mutations in cancer. Welcome Trust, Sanger Institute, Cambridge, UK; 2011. Available from: http://www.sanger. ac.uk/perl/genetics/CGP/cosmic? action=gene&ln=PTEN [Cited 11 November 2012]
4. Tumorscape: copy number alterations across multiple cancer types. The Broad Institute of MIT and Harvard, US. Available from: http://www. broadinstitute.org/tumorscape/pages/portalHome.jsf# [Cited 14 November 2012]
5. Govender D, Chetty R. Gene of the month: PTEN. J Clin Pathol 2012;65(7):601-3
6. Gericke A, Munson M, Ross AH. Regulation of the PTEN phosphatase. Gene 2006;374:1-9 (Pubitemid 43737118)
7. Miller SJ, Lou DY, Seldin DC, et al. Direct identification of PTEN phosphorylation sites. FEBS Lett 2002;528(1-3):145-53 (Pubitemid 35258015)
8. Torres J, Pulido R. The tumor suppressor PTEN is phosphorylated by the protein kinase CK2 at its C terminus. Implications for PTEN stability to proteasome-mediated degradation. J Biol Chem 2001;276(2):993-8 (Pubitemid 32096519)
9. Mehenni H, Lin-Marq N, Buchet-Poyau K, et al. LKB1 interacts with and phosphorylates PTEN: a functional link between two proteins involved in cancer predisposing syndromes. Hum Mol Genet 2005;14(15):2209-1
10. Al-Khouri AM, Ma Y, Togo SH, et al. Cooperative phosphorylation of the tumor suppressor phosphatase and tensin homologue (PTEN) by casein kinases and glycogen synthase kinase 3beta. J Biol Chem 2005;280(42):35195-202 (Pubitemid 41532706)
11. Wu Y, Dowbenko D, Spencer S, et al. Interaction of the tumor suppressor PTEN/MMAC with a PDZ domain of MAGI3, a novel membrane-associated guanylate kinase. J Biol Chem 2000;275(28):21477-85 (Pubitemid 30481851)
12. Wu X, Hepner K, Castelino-Prabhu S, et al. Evidence for regulation of the PTEN tumor suppressor by a membrane-localized multi-PDZ domain containing scaffold protein MAGI-2. Proc Natl Acad Sci USA 2000;97(8):4233-8 (Pubitemid 30226116)
13. Valiente M, Andres-Pons A, Gomar B, et al. Binding of PTEN to specific PDZ domains contributes to PTEN protein stability and phosphorylation by microtubule-associated serine/threonine kinases. J Biol Chem 2005;280(32):28936-43 (Pubitemid 41161339)
14. Okahara F, Itoh K, Nakagawara A, et al. Critical role of PICT-1, a tumor suppressor candidate, in phosphatidylinositol 3,4,5-trisphosphate signals and tumorigenic transformation. Mol Biol Cell 2006;17(11):4888-95 (Pubitemid 44665757)
15. Yim EK, Peng G, Dai H, et al. Rak functions as a tumor suppressor by regulating PTEN protein stability and function. Cancer Cell 2009;15(4):304-1
16. Li Z, Dong X, Wang Z, et al. Regulation of PTEN by rho small GTPases. Nat Cell Biol 2005;7(4):399-404 (Pubitemid 40533130)
17. Hubner A, Mulholland DJ, Standen CL, et al. JNK and PTEN cooperatively control the development of invasive adenocarcinoma of the prostate. Proc Natl Acad Sci USA 2012;109(30):12046-51
18. Liang K, Esteva FJ, Albarracin C, et al. Recombinant human erythropoietin antagonizes trastuzumab treatment of breast cancer cells via Jak2-mediated Src activation and PTEN inactivation. Cancer Cell 2010;18(5):423-35
19. Schmid AC, Byrne RD, Vilar R, Woscholski R. Bisperoxovanadium compounds are potent PTEN inhibitors. FEBS Lett 2004;566(1-3):35-8 (Pubitemid 38625928)
20. Horie Y, Suzuki A, Kataoka E, et al. Hepatocyte-specific pten deficiency results in steatohepatitis and hepatocellular carcinomas. J Clin Invest 2004;113(12):1774-83 (Pubitemid 39071669)
21. Ning K, Miller LC, Laidlaw HA, et al. Leptin-dependent phosphorylation of PTEN mediates actin restructuring and activation of ATP-sensitive K+ channels. J Biol Chem 2009;284(14):9331-40
22. Oudit GY, Kassiri Z, Zhou J, et al. Loss of PTEN attenuates the development of pathological hypertrophy and heart failure in response to biomechanical stress. Cardiovasc Res 2008;78(3):505-14 (Pubitemid 351769769)
23. Butler MG, Dasouki MJ, Zhou XP, et al. Subset of individuals with autism spectrum disorders and extreme macrocephaly associated with germline PTEN tumour suppressor gene mutations. J Med Genet 2005;42(4):318-21 (Pubitemid 40523954)
24. Kwon CH, Luikart BW, Powell CM, et al. Pten regulates neuronal arborization and social interaction in mice. Neuron 2006;50(3):377-88
25. Gupta A, Dey CS. PTEN, a widely known negative regulator of insulin/PI3K signaling, positively regulates neuronal insulin resistance. Mol Biol Cell 2012;23(19):3882-98
26. Valente EM, Abou-Sleiman PM, Caputo V, et al. Hereditary early-onset parkinson's disease caused by mutations in PINK1. Science 2004;304(5674):1158-60 (Pubitemid 38661852)
27. Valente EM, Salvi S, Ialongo T, et al. PINK1 mutations are associated with sporadic early-onset parkinsonism. Ann Neurol 2004;56(3):336-41 (Pubitemid 39166552)
28. Kwak YG, Song CH, Yi HK, et al. Involvement of PTEN in airway hyperresponsiveness and inflammation in bronchial asthma. J Clin Invest 2003;111(7):1083-92 (Pubitemid 36397485)
29. Jia G, Mitra AK, Gangahar DM, Agrawal DK. Regulation of cell cycle entry by PTEN in smooth muscle cell proliferation of human coronary artery bypass conduits. J Cell Mol Med 2009;13(3):547-54
30. Mitra AK, Jia G, Gangahar DM, Agrawal DK. Temporal PTEN inactivation causes proliferation of saphenous vein smooth muscle cells of human CABG conduits. J Cell Mol Med 2009;13(1):177-8
31. Chen Z, Trotman LC, Shaffer D, et al. Crucial role of p53-dependent cellular senescence in suppression of pten-deficient tumorigenesis. Nature 2005;436(7051):725-30 (Pubitemid 41117277)
32. Palomero T, Sulis ML, Cortina M, et al. Mutational loss of PTEN induces resistance to NOTCH1 inhibition in T-cell leukemia. Nat Med 2007;13(10):1203-10 (Pubitemid 47530629)
33. Hettinger K, Vikhanskaya F, Poh MK, et al. C-jun promotes cellular survival by suppression of PTEN. Cell Death Differ 2007;14(2):218-29 (Pubitemid 46092225)
34. Chow JY, Quach KT, Cabrera BL, et al. RAS/ERK modulates TGFbeta-regulated PTEN expression in human pancreatic adenocarcinoma cells. Carcinogenesis 2007;28(11):2321-7 (Pubitemid 350111590)
35. Vasudevan KM, Burikhanov R, Goswami A, Rangnekar VM. Suppression of PTEN expression is essential for antiapoptosis and cellular transformation by oncogenic ras. Cancer Res 2007;67(21):10343-50 (Pubitemid 350070809)
36. Xia D, Srinivas H, Ahn YH, et al. Mitogen-activated protein kinase kinase-4 promotes cell survival by decreasing PTEN expression through an NF kappa B-dependent pathway. J Biol Chem 2007;282(6):3507-19 (Pubitemid 47084470)
37. Wang X, Trotman LC, Koppie T, et al. NEDD4-1 is a proto-oncogenic ubiquitin ligase for PTEN. Cell 2007;128(1):129-3
38. Maddika S, Kavela S, Rani N, et al. WWP2 is an E3 ubiquitin ligase for PTEN. Nat Cell Biol 2011;13(6):728-33
39. Lu Y, Yu Q, Liu JH, et al. Src family protein-tyrosine kinases alter the function of PTEN to regulate phosphatidylinositol 3-kinase/AKT cascades. J Biol Chem 2003;278(41):40057-66 (Pubitemid 37248572)
40. Gustin JA, Maehama T, Dixon JE, Donner DB. The PTEN tumor suppressor protein inhibits tumor necrosis factor-induced nuclear factor kappa B activity. J Biol Chem 2001;276(29):27740-4
41. Vivanco I, Palaskas N, Tran C, et al. Identification of the JNK signaling pathway as a functional target of the tumor suppressor PTEN. Cancer Cell 2007;11(6):555-69 (Pubitemid 46856910)
42. Choi BH, Lee KS, Dai W. Phosphorylation and regulation of PTEN by polo-like kinase 1. Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; March 31-April 4; Chicago, IL, Philadelphia (PA). Am Assoc Cancer Res 2012;72(8 Suppl):abstract # 2048
43. Subauste MC, Nalbant P, Adamson ED, Hahn KM. Vinculin controls PTEN protein level by maintaining the interaction of the adherens junction protein beta-catenin with the scaffolding protein MAGI-2. J Biol Chem 2005;280(7):5676-81 (Pubitemid 40280047)
44. Bayascas JR, Leslie NR, Parsons R, et al. Hypomorphic mutation of PDK1 suppresses tumorigenesis in PTEN(+/-) mice. Curr Biol 2005;15(20):1839-46 (Pubitemid 41501519)
45. Baritaki S, Militello L, Malaponte G, et al. The anti-CD20 mAb LFB-R603 interrupts the dysregulated NF-kappaB/snail/RKIP/PTEN resistance loop in B-NHL cells: role in sensitization to TRAIL apoptosis. Int J Oncol 2011;38(6):1683-94
46. Fisson S, Fridman C, Urbain R; inventors; LFB Biotechnologies, assignee. Use of anti-CD20 antibody for treating primary intraocular lymphoma. US20120100133; 2012
47. Nagata Y, Lan KH, Zhou X, et al. PTEN activation contributes to tumor inhibition by trastuzumab, and loss of PTEN predicts trastuzumab resistance in patients. Cancer Cell 2004;6(2):117-12
48. Agresta S, Klencke B; inventors; Genentech I, assignee. Methods of treating metastatic breast cancer with trastuzumab-MCC-DM1. US20110165155A1; 2011
49. Alder M, Grauschofp U, Mahler HC, Stauch OB; inventors; Genentech I, assignee. Subcutaneous anti-Her2 antibody formulations and uses thereof. US20110044977A1; 2011
50. Goltsov A, Faratian D, Langdon SP, et al. Features of the reversible sensitivity-resistance transition in PI3K/PTEN/AKT signalling network after HER2 inhibition. Cell Signal 2012;24(2):493-504
51. Suzuki E, Umezawa K, Bonavida B. Rituximab inhibits the constitutively activated PI3K-akt pathway in B-NHL cell lines: involvement in chemosensitization to drug-induced apoptosis. Oncogene 2007;26(42):6184-93 (Pubitemid 47414382)
52. Lopez AG; inventor; Biogen Idec, Inc., assignee. Combination therapies for B-cell lymphomas comprising administration of anti-CD20 antibody. EP1974747B1; 2012
53. Frattini M, Saletti P, Romagnani E, et al. PTEN loss of expression predicts cetuximab efficacy in metastatic colorectal cancer patients. Br J Cancer 2007;97(8):1139-45 (Pubitemid 47587019)
54. Francoise B, David G, Richard MK, Joseph S; inventors; RHONE-POULENC RORER INTERNATIONAL (HOLDINGS), INC., assignee. Therapeutic compositions containing monoclonal antibodies specific to human epidermal growth factor receptor. EP0667165B1; 2002
55. Abouantoun TJ, Castellino RC, MacDonald TJ. Sunitinib induces PTEN expression and inhibits PDGFR signaling and migration of medulloblastoma cells. J Neurooncol 2011;101(2):215-26
56. Tang CT, Miller TA, Li X, et al. inventors; Sugen, Inc., & Pharmacia Upjohn Co., assignee. Pyrrole substituted 2-indolinone protein kinase inhibitors. US6573293; 2003
57. She QB, Solit D, Basso A, Moasser MM. Resistance to gefitinib in PTEN-null HER-overexpressing tumor cells can be overcome through restoration of PTEN function or pharmacologic modulation of constitutive phosphatidylinositol 3¢-kinase/akt pathway signaling. Clin Cancer Res 2003;9(12):4340-6 (Pubitemid 37248389)
58. Agus BD; inventor; Cedars-Sinai Medical Center, assignee. Gefitinib (iressa) for the treatment of cancer. EP1509230B1; 2007
59. Sos ML, Koker M, Weir BA, et al. PTEN loss contributes to erlotinib resistance in EGFR-mutant lung cancer by activation of Akt and EGFR. Cancer Res 2009;69(8):3256-61
60. Norris T, Ferry G, Raggon JW, et al. inventors; OSI Pharmaceuticals I, assignee. Stable polymorph on N-(3-ethynylphenyl)-6, 7-bis(2methoxyethoxy)-4- quinazolinamine hydochloride, methods of production, and pharmaceutical uses thereof. US6900221; 2005
61. Shen YH, Zhang L, Gan Y, et al. Up-regulation of PTEN (phosphatase and tensin homolog deleted on chromosome ten) mediates p38 MAPK stress signal-induced inhibition of insulin signaling. A cross-talk between stress signaling and insulin signaling in resistin-treated human endothelial cells. J Biol Chem 2006;281(12):7727-36 (Pubitemid 43847386)
62. Ghosh-Choudhury N, Mandal CC, Ghosh-Choudhury N, Ghosh Choudhury G. Simvastatin induces derepression of PTEN expression via NFkappaB to inhibit breast cancer cell growth. Cell Signal 2010;22(5):749-58
63. Kubela R, Radhakrishnan J; inventors; Apotex I, assignee. Process for producing simvastatin and analogs thereof. US5393893; 1995
64. Teresi RE, Shaiu CW, Chen CS, et al. Increased PTEN expression due to transcriptional activation of PPARgamma by lovastatin and rosiglitazone. Int J Cancer 2006;118(10):2390-8
65. Monaghan RL, Alberts AW, Hoffman CH, Schonberg GA; inventors; Merck & Co, assignee. Hypocholesteremic fermentation products and process of preparation. US4231938; 1980
66. Patel L, Pass I, Coxon P, et al. Tumor suppressor and anti-inflammatory actions of PPARgamma agonists are mediated via upregulation of PTEN. Curr Biol 2001;11(10):764-8 (Pubitemid 32442793)
67. Isebaert SF, Swinnen JV, McBride WH, Haustermans KM. Insulin-like growth factor-type 1 receptor inhibitor NVP-AEW541 enhances radiosensitivity of PTEN wild-type but not PTEN-deficient human prostate cancer cells. Int J Radiat Oncol Biol Phys 2011;81(1):239-47
68. Bonavida B, Palladino MA; inventors; The Regents of the University of California & Nereus Pharmaceuticals, Inc., assignee. Methods of sensitizing cancer to therapy-induced cytotoxicity. US20090148445A1; 2009
69. Berggren M, Sittadjody S, Song Z, et al. Sodium selenite increases the activity of the tumor suppressor protein, PTEN, in DU-145 prostate cancer cells. Nutr Cancer 2009;61(3):322-31
70. Stambolic V, MacPherson D, Sas D, et al. Regulation of PTEN transcription by p53. Mol Cell 2001;8(2):317-25 (Pubitemid 32831549)
71. Virolle T, Adamson ED, Baron V, et al. The egr-1 transcription factor directly activates PTEN during irradiation-induced signalling. Nat Cell Biol 2001;3(12):1124-8 (Pubitemid 33130464)
72. Yoshimi A, Goyama S, Watanabe-Okochi N, et al. Evi1 represses PTEN expression and activates PI3K/AKT/mTOR via interactions with polycomb proteins. Blood 2011;117(13):3617-28
73. Olson MV, Alonso MM, Gomez-Manzano C, et al. E2F1 transcriptionally activates PTEN [abstract #2808]. Proc Am Assoc Cancer Res. Cellular and Molecular Biology 38: oncogenic pathways in cancer; Philadelphia (PA). Am Assoc Cancer Res 2005;46(1):661
74. Wang Y, He X, Ngeow J, Eng C. GATA2 negatively regulates PTEN by preventing nuclear translocation of androgen receptor and by androgen-independent suppression of PTEN transcription in breast cancer. Hum Mol Genet 2012;21(3):569-76
75. Escriva M, Peiro S, Herranz N, et al. Repression of PTEN phosphatase by Snail1 transcriptional factor during gamma radiation-induced apoptosis. Mol Cell Biol 2008;28(5):1528-40
76. Vasudevan KM, Gurumurthy S, Rangnekar VM. Suppression of PTEN expression by NF-kappa B prevents apoptosis. Mol Cell Biol 2004;24(3):1007-21 (Pubitemid 38112166)
77. Giagulli C, Marsico S, Magiera AK, et al. Opposite effects of HIV-1 p17 variants on PTEN activation and cell growth in B cells. PLoS One 2011;6(3):e17831
78. Perdigoto AL, Chaudhry N, Barnes GN, et al. A novel role for PTEN in the inhibition of neurite outgrowth by myelin-associated glycoprotein in cortical neurons. Mol Cell Neurosci 2011;46(1):235-44
79. Sumitomo M, Iwase A, Zheng R, et al. Synergy in tumor suppression by direct interaction of neutral endopeptidase with PTEN. Cancer Cell 2004;5(1):67-78 (Pubitemid 38121597)
80. Yang S, Kim HM. The RhoA-ROCK-PTEN pathway as a molecular switch for anchorage dependent cell behavior. Biomaterials 2012;33(10):2902-15
81. Vemula S, Shi J, Hanneman P, et al. ROCK1 functions as a suppressor of inflammatory cell migration by regulating PTEN phosphorylation and stability. Blood 2010;115(9):1785-96
82. Zhu Z, Jia J, Lu R, et al. Expression of PTEN, p27, p21 and AKT mRNA and protein in human BEL-7402 hepatocarcinoma cells in transplanted tumors of nude mice treated with the tripeptide tyroservatide (YSV). Int J Cancer 2006;118(6):1539-44
83. Bhoopathi P, Gorantla B, Sailaja GS, et al. SPARC overexpression inhibits cell proliferation in neuroblastoma and is partly mediated by tumor suppressor protein PTEN and AKT. PLoS One 2012;7(5):e36093
84. Oinuma I, Ito Y, Katoh H, Negishi M. Semaphorin 4D/plexin-B1 stimulates PTEN activity through R-ras GTPase-activating protein activity, inducing growth cone collapse in hippocampal neurons. J Biol Chem 2010;285(36):28200-9
85. Ma L, Chang N, Guo S, et al. CSIG inhibits PTEN translation in replicative senescence. Mol Cell Biol 2008;28(20):6290-301
86. Lima-Fernandes E, Enslen H, Camand E, et al. Distinct functional outputs of PTEN signalling are controlled by dynamic association with beta-arrestins. EMBO J 2011;30(13):2557-68
87. Verma A, Guha S, Wang H, et al. Tissue transglutaminase regulates focal adhesion kinase/AKT activation by modulating PTEN expression in pancreatic cancer cells. Clin Cancer Res 2008;14(7):1997-2005 (Pubitemid 351551108)
88. Lu D, Han C, Wu T. Microsomal prostaglandin E synthase-1 inhibits PTEN and promotes experimental cholangiocarcinogenesis and tumor progression. Gastroenterology 2011;140(7):2084-9
89. Papakonstanti EA, Ridley AJ, Vanhaesebroeck B. The p110delta isoform of PI 3-kinase negatively controls RhoA and PTEN. EMBO J 2007;26(13):3050-61 (Pubitemid 47057501)
90. Fine B, Hodakoski C, Koujak S, et al. Activation of the PI3K pathway in cancer through inhibition of PTEN by exchange factor P-REX2a. Science 2009;325(5945):1261-5
91. Okumura K, Mendoza M, Bachoo RM, et al. PCAF modulates PTEN activity. J Biol Chem 2006;281(36):26562-8 (Pubitemid 44401865)
92. He L, Ingram A, Rybak AP, Tang D. Shank-interacting protein-like 1 promotes tumorigenesis via PTEN inhibition in human tumor cells. J Clin Invest 2010;120(6):2094-108
93. He L, Fan C, Kapoor A, et al. Alpha-mannosidase 2C1 attenuates PTEN function in prostate cancer cells. Nat Commun 2011;2:307
94. Seo JH, Ahn Y, Lee SR, et al. The major target of the endogenously generated reactive oxygen species in response to insulin stimulation is phosphatase and tensin homolog and not phosphoinositide-3 kinase (PI-3 kinase) in the PI-3 kinase/akt pathway. Mol Biol Cell 2005;16(1):348-57 (Pubitemid 40024316)
95. Takahashi Y, Morales FC, Kreimann EL, Georgescu MM. PTEN tumor suppressor associates with NHERF proteins to attenuate PDGF receptor signaling. EMBO J 2006;25(4):910-12
96. Edwin F, Singh R, Endersby R, et al. The tumor suppressor PTEN is necessary for human sprouty 2-mediated inhibition of cell proliferation. J Biol Chem 2006;281(8):4816-22 (Pubitemid 43847743)