Nilotinib, an approved leukemia drug, inhibits smoothened signaling in Hedgehog-dependent medulloblastoma
Autoři:
Kirti Kandhwal Chahal aff001; Jie Li aff003; Irina Kufareva aff001; Milind Parle aff002; Donald L. Durden aff004; Robert J. Wechsler-Reya aff005; Clark C. Chen aff003; Ruben Abagyan aff001
Působiště autorů:
Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego (UCSD), La Jolla, California, United States of America
aff001; Department of Pharmaceutical Sciences, G.J. University of Science and Technology, Hisar, India
aff002; Department of Neurosurgery, Minneapolis, Minnesota, United States of America
aff003; Department of Pediatrics, Moores Cancer Center, School of Medicine, UCSD and Rady Children’s Hospital, San Diego, La Jolla, California, United States of America
aff004; Tumor Initiation and Maintenance Program, NCI-Designated Cancer Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, California, United States of America
aff005
Vyšlo v časopise:
PLoS ONE 14(9)
Kategorie:
Research Article
prolekare.web.journal.doi_sk:
https://doi.org/10.1371/journal.pone.0214901
Souhrn
Dysregulation of the seven-transmembrane (7TM) receptor Smoothened (SMO) and other components of the Hedgehog (Hh) signaling pathway contributes to the development of cancers including basal cell carcinoma (BCC) and medulloblastoma (MB). However, SMO-specific antagonists produced mixed results in clinical trials, marked by limited efficacy and high rate of acquired resistance in tumors. Here we discovered that Nilotinib, an approved inhibitor of several kinases, possesses an anti-Hh activity, at clinically achievable concentrations, due to direct binding to SMO and inhibition of SMO signaling. Nilotinib was more efficacious than the SMO-specific antagonist Vismodegib in inhibiting growth of two Hh-dependent MB cell lines. It also reduced tumor growth in subcutaneous MB mouse xenograft model. These results indicate that in addition to its known activity against several tyrosine-kinase-mediated proliferative pathways, Nilotinib is a direct inhibitor of the Hh pathway. The newly discovered extension of Nilotinib’s target profile holds promise for the treatment of Hh-dependent cancers.
Klíčová slova:
Biology and life sciences – Cell biology – Research and analysis methods – Medicine and health sciences – Cellular structures and organelles – Pharmacology – Oncology – Cancer treatment – Cancers and neoplasms – Cell membranes – Signal transduction – Bioassays and physiological analysis – Cell signaling – Chemical characterization – Binding analysis – Blastomas – Hedgehog signaling – Cell analysis – Cell viability testing – Medulloblastoma – Drug screening – Fluorescence competition
Zdroje
1. Robbins DJ, Fei DL, Riobo NA. The Hedgehog signal transduction network. Sci Signal. 2012 Oct 16;5(246):re6. doi: 10.1126/scisignal.2002906 23074268
2. Huang H-C, Klein PS, Adler P, Wang Y, Macke J, Abella B, et al. The Frizzled family: receptors for multiple signal transduction pathways. Genome Biol. 2004;5(7):234. doi: 10.1186/gb-2004-5-7-234 15239825
3. Carpenter D, Stone DM, Brush J, Ryan A, Armanini M, Frantz G, et al. Characterization of two patched receptors for the vertebrate hedgehog protein family. Proc Natl Acad Sci U S A. 1998 Nov 10;95(23):13630–4. doi: 10.1073/pnas.95.23.13630 9811851
4. Huang P, Nedelcu D, Watanabe M, Jao C, Kim Y, Liu J, et al. Cellular Cholesterol Directly Activates Smoothened in Hedgehog Signaling. Cell. 2016;166(5):1176–1187.e14. doi: 10.1016/j.cell.2016.08.003 27545348
5. Lum L, Beachy PA. The Hedgehog response network: sensors, switches, and routers. Science. 2004 Jun 18;304(5678):1755–9. doi: 10.1126/science.1098020 15205520
6. Caro I, Low JA. The role of the hedgehog signaling pathway in the development of basal cell carcinoma and opportunities for treatment. Clin Cancer Res Off J Am Assoc Cancer Res. 2010 Jul 1;16(13):3335–9.
7. Romer J, Curran T. Targeting medulloblastoma: small-molecule inhibitors of the Sonic Hedgehog pathway as potential cancer therapeutics. Cancer Res. 2005 Jun 15;65(12):4975–8. doi: 10.1158/0008-5472.CAN-05-0481 15958535
8. Zhao C, Chen A, Jamieson CH, Fereshteh M, Abrahamsson A, Blum J, et al. Hedgehog signalling is essential for maintenance of cancer stem cells in myeloid leukaemia. Nature. 2009 Apr 9;458(7239):776–9. doi: 10.1038/nature07737 19169242
9. Jones S, Zhang X, Parsons DW, Lin JC-H, Leary RJ, Angenendt P, et al. Core signaling pathways in human pancreatic cancers revealed by global genomic analyses. Science. 2008 Sep 26;321(5897):1801–6. doi: 10.1126/science.1164368 18772397
10. Clement V, Sanchez P, de Tribolet N, Radovanovic I, Ruiz i Altaba A. HEDGEHOG-GLI1 signaling regulates human glioma growth, cancer stem cell self-renewal, and tumorigenicity. Curr Biol CB. 2007 Jan 23;17(2):165–72. doi: 10.1016/j.cub.2006.11.033 17196391
11. Smoll NR, Drummond KJ. The incidence of medulloblastomas and primitive neurectodermal tumours in adults and children. J Clin Neurosci Off J Neurosurg Soc Australas. 2012 Nov;19(11):1541–4.
12. Cochrane CR, Szczepny A, Watkins DN, Cain JE. Hedgehog Signaling in the Maintenance of Cancer Stem Cells. Cancers. 2015;7(3):1554–85. doi: 10.3390/cancers7030851 26270676
13. Emmenegger BA, Wechsler-Reya RJ. Stem cells and the origin and propagation of brain tumors. J Child Neurol. 2008 Oct;23(10):1172–8. doi: 10.1177/0883073808321062 18952583
14. Bao S, Wu Q, McLendon RE, Hao Y, Shi Q, Hjelmeland AB, et al. Glioma stem cells promote radioresistance by preferential activation of the DNA damage response. Nature. 2006 Dec 7;444(7120):756–60. doi: 10.1038/nature05236 17051156
15. Justilien V, Fields AP. Molecular pathways: novel approaches for improved therapeutic targeting of Hedgehog signaling in cancer stem cells. Clin Cancer Res Off J Am Assoc Cancer Res. 2015 Feb 1;21(3):505–13.
16. Rimkus TK, Carpenter RL, Qasem S, Chan M, Lo HW. Targeting the sonic hedgehog signaling pathway: Review of smoothened and GLI inhibitors. Vol. 8, Cancers. 2016.
17. Chen JK, Taipale J, Cooper MK, Beachy PA. Inhibition of Hedgehog signaling by direct binding of cyclopamine to Smoothened. Genes Dev. 2002 Nov 1;16(21):2743–8. doi: 10.1101/gad.1025302 12414725
18. Kieran MW. Targeted treatment for sonic hedgehog-dependent medulloblastoma. Neuro-Oncol. 2014 Aug;16(8):1037–47. doi: 10.1093/neuonc/nou109 24951114
19. Metcalfe C, de Sauvage FJ. Hedgehog Fights Back: Mechanisms of Acquired Resistance against Smoothened Antagonists. Cancer Res. 2011 Aug 1;71(15):5057–61. doi: 10.1158/0008-5472.CAN-11-0923 21771911
20. Yauch RL, Dijkgraaf GJP, Alicke B, Januario T, Ahn CP, Holcomb T, et al. Smoothened mutation confers resistance to a Hedgehog pathway inhibitor in medulloblastoma. Science. 2009 Oct 23;326(5952):572–4. doi: 10.1126/science.1179386 19726788
21. Gonda TJ, Ramsay RG. Directly targeting transcriptional dysregulation in cancer. Nat Rev Cancer. 2015 Oct 23;15(11):686–94. doi: 10.1038/nrc4018 26493648
22. Chahal KK, Parle M, Abagyan R. Hedgehog pathway and smoothened inhibitors in cancer therapies: Anticancer Drugs. 2018 Jun;29(5):387–401. doi: 10.1097/CAD.0000000000000609 29537987
23. Kool M, Jones DTW, Jäger N, Northcott PA, Pugh TJ, Hovestadt V, et al. Genome sequencing of SHH medulloblastoma predicts genotype-related response to smoothened inhibition. Cancer Cell. 2014 Mar 17;25(3):393–405. doi: 10.1016/j.ccr.2014.02.004 24651015
24. Bozic I, Reiter JG, Allen B, Antal T, Chatterjee K, Shah P, et al. Evolutionary dynamics of cancer in response to targeted combination therapy. eLife. 2013 Jan;2:e00747. doi: 10.7554/eLife.00747 23805382
25. Komarova NL, Katouli AA, Wodarz D. Combination of Two but Not Three Current Targeted Drugs Can Improve Therapy of Chronic Myeloid Leukemia. Seoighe C, editor. PLoS ONE. 2009 Feb 10;4(2):e4423. doi: 10.1371/journal.pone.0004423 19204794
26. Soria J-C, Massard C, Izzedine H. From Theoretical Synergy to Clinical Supra-Additive Toxicity. J Clin Oncol. 2009 Mar;27(9):1359–1361. doi: 10.1200/JCO.2008.20.8595 19224836
27. Ogino S, Nishihara R, VanderWeele TJ, Wang M, Nishi A, Lochhead P, et al. Review Article: The Role of Molecular Pathological Epidemiology in the Study of Neoplastic and Non-neoplastic Diseases in the Era of Precision Medicine. Epidemiol Camb Mass. 2016 Jul;27(4):602–11.
28. Morgillo F, Amendola G, Della Corte CM, Giacomelli C, Botta L, Di Maro S, et al. Dual MET and SMO Negative Modulators Overcome Resistance to EGFR Inhibitors in Human Nonsmall Cell Lung Cancer. J Med Chem. 2017 Sep 14;60(17):7447–58. doi: 10.1021/acs.jmedchem.7b00794 28787156
29. Wang C, Wu H, Evron T, Vardy E, Han GW, Huang X-P, et al. Structural basis for Smoothened receptor modulation and chemoresistance to anticancer drugs. Nat Commun. 2014 Jan;5:4355. doi: 10.1038/ncomms5355 25008467
30. Totrov M, Abagyan R. Flexible protein-ligand docking by global energy optimization in internal coordinates. Proteins. 1997;Suppl 1:215–20.
31. Kufareva I, Chen Y-C, Ilatovskiy A V, Abagyan R. Compound activity prediction using models of binding pockets or ligand properties in 3D. Curr Top Med Chem. 2012 Jan;12(17):1869–82. doi: 10.2174/156802612804547335 23116466
32. Chen Y-C, Totrov M, Abagyan R. Docking to multiple pockets or ligand fields for screening, activity prediction and scaffold hopping. Future Med Chem. 2014 Jan;6(16):1741–55. doi: 10.4155/fmc.14.113 25407367
33. Manley PW, Cowan-Jacob SW, Mestan J. Advances in the structural biology, design and clinical development of Bcr-Abl kinase inhibitors for the treatment of chronic myeloid leukaemia. Biochim Biophys Acta BBA—Proteins Proteomics. 2005;1754(1):3–13.
34. Hantschel O, Rix U, Superti-Furga G. Target spectrum of the BCR-ABL inhibitors imatinib, nilotinib and dasatinib. Leuk Lymphoma. 2008 Apr 1;49(4):615–9. doi: 10.1080/10428190801896103 18398720
35. Wang C, Wu H, Katritch V, Han GW, Huang X-P, Liu W, et al. Structure of the human smoothened receptor bound to an antitumour agent. Nature. 2013 May 16;497(7449):338–43. doi: 10.1038/nature12167 23636324
36. Totrov M. Atomic property fields: generalized 3D pharmacophoric potential for automated ligand superposition, pharmacophore elucidation and 3D QSAR. Chem Biol Drug Des. 2008 Jan;71(1):15–27. doi: 10.1111/j.1747-0285.2007.00605.x 18069986
37. Akare UR, Bandaru S, Shaheen U, Singh PK, Tiwari G, Singare P, et al. Molecular docking approaches in identification of High affinity inhibitors of Human SMO receptor. Bioinformation. 2014;10(12):737–42. doi: 10.6026/97320630010737 25670876
38. Huang P, Zheng S, Wierbowski BM, Kim Y, Nedelcu D, Aravena L, et al. Structural Basis of Smoothened Activation in Hedgehog Signaling. Cell [Internet]. 2018 May [cited 2018 Jun 19]; http://linkinghub.elsevier.com/retrieve/pii/S0092867418305221
39. Martarelli D, Pompei P, Baldi C, Mazzoni G. Mebendazole inhibits growth of human adrenocortical carcinoma cell lines implanted in nude mice. Cancer Chemother Pharmacol. 2008 Apr 21;61(5):809–17. doi: 10.1007/s00280-007-0538-0 17581752
40. Nygren P, Fryknäs M, Agerup B, Larsson R. Repositioning of the anthelmintic drug mebendazole for the treatment for colon cancer. J Cancer Res Clin Oncol. 2013 Dec;139(12):2133–40. doi: 10.1007/s00432-013-1539-5 24135855
41. Eleutherakis-Papaiakovou V, Bamias A, Dimopoulos MA. Thalidomide in cancer medicine. Ann Oncol. 2004 Aug 1;15(8):1151–60. doi: 10.1093/annonc/mdh300 15277253
42. Su B, Chen S. Lead optimization of COX-2 inhibitor nimesulide analogs to overcome aromatase inhibitor resistance in breast cancer cells. Bioorg Med Chem Lett. 2009 Dec 1;19(23):6733–5. doi: 10.1016/j.bmcl.2009.09.109 19854050
43. Byrne EFX, Sircar R, Miller PS, Hedger G, Luchetti G, Nachtergaele S, et al. Structural basis of Smoothened regulation by its extracellular domains. Nature. 2016 Jul 20;535(7613):517–22. doi: 10.1038/nature18934 27437577
44. Larsen AR, Bai R-Y, Chung JH, Borodovsky A, Rudin CM, Riggins GJ, et al. Repurposing the antihelmintic mebendazole as a hedgehog inhibitor. Mol Cancer Ther. 2015;14(1):3–13. doi: 10.1158/1535-7163.MCT-14-0755-T 25376612
45. Giles FJ, Yin OQP, Sallas WM, Le Coutre PD, Woodman RC, Ottmann OG, et al. Nilotinib population pharmacokinetics and exposure-response analysis in patients with imatinib-resistant or -intolerant chronic myeloid leukemia. Eur J Clin Pharmacol. 2013;69(4):813–23. doi: 10.1007/s00228-012-1385-4 23052406
46. Therapeutic Goods Administration. Australian Public Assessment Report for Nilotinib. 2011.
47. Bar EE, Chaudhry A, Lin A, Fan X, Schreck K, Matsui W, et al. Cyclopamine-mediated hedgehog pathway inhibition depletes stem-like cancer cells in glioblastoma. Stem Cells Dayt Ohio. 2007 Oct;25(10):2524–33.
48. Weierstall U, James D, Wang C, White TA, Wang D, Liu W, et al. Lipidic cubic phase injector facilitates membrane protein serial femtosecond crystallography. Nat Commun. 2014 Feb 14;5:1119–26.
49. Tao H, Jin Q, Koo D-I, Liao X, Englund NP, Wang Y, et al. Small Molecule Antagonists in Distinct Binding Modes Inhibit Drug-Resistant Mutant of Smoothened. Vol. 18, Chemistry & Biology. 2011.
50. Singh AR, Joshi S, Zulcic M, Alcaraz M, Garlich JR, Morales GA, et al. PI-3K Inhibitors Preferentially Target CD15+ Cancer Stem Cell Population in SHH Driven Medulloblastoma. Castresana JS, editor. PLOS ONE. 2016 Mar 3;11(3):e0150836. doi: 10.1371/journal.pone.0150836 26938241
51. Jacobsen PF, Jenkyn DJ, Papadimitriou JM. Establishment of a Human Medulloblastoma Cell Line and Its Heterotransplantation into Nude Mice: J Neuropathol Exp Neurol. 1985 Sep;44(5):472–85. doi: 10.1097/00005072-198509000-00003 2993532
52. Götschel F, Berg D, Gruber W, Bender C, Eberl M, Friedel M, et al. Synergism between Hedgehog-GLI and EGFR Signaling in Hedgehog-Responsive Human Medulloblastoma Cells Induces Downregulation of Canonical Hedgehog-Target Genes and Stabilized Expression of GLI1. Uversky VN, editor. PLoS ONE. 2013 Jun 10;8(6):e65403. doi: 10.1371/journal.pone.0065403 23762360
53. Lee J, Kotliarova S, Kotliarov Y, Li A, Su Q, Donin NM, et al. Tumor stem cells derived from glioblastomas cultured in bFGF and EGF more closely mirror the phenotype and genotype of primary tumors than do serum-cultured cell lines. Cancer Cell. 2006 May 1;9(5):391–403. doi: 10.1016/j.ccr.2006.03.030 16697959
54. Singh SK, Hawkins C, Clarke ID, Squire JA, Bayani J, Hide T, et al. Identification of human brain tumour initiating cells. Nature. 2004 Nov 18;432(7015):396–401. doi: 10.1038/nature03128 15549107
55. Conradt L, Godl K, Schaab C, Tebbe A, Eser S, Diersch S, et al. Disclosure of erlotinib as a multikinase inhibitor in pancreatic ductal adenocarcinoma. Neoplasia N Y N. 2011 Nov;13(11):1026–34.
56. Shi D, Khan F, Abagyan R. Extended Multitarget Pharmacology of Anticancer Drugs. J Chem Inf Model. 2019 Jun 24;59(6):3006–17. doi: 10.1021/acs.jcim.9b00031 31025863
57. Higdon R, Kala J, Wilkins D, Yan J, Sethi M, Lin L, et al. Integrated Proteomic and Transcriptomic-Based Approaches to Identifying Signature Biomarkers and Pathways for Elucidation of Daoy and UW228 Subtypes. Proteomes. 2017 Feb 3;5(4):5.
58. Yang Z-J, Ellis T, Markant SL, Read T-A, Kessler JD, Bourboulas M, et al. Medulloblastoma can be initiated by deletion of Patched in lineage-restricted progenitors or stem cells. Cancer Cell. 2008 Aug;14(2):135–45. doi: 10.1016/j.ccr.2008.07.003 18691548
59. Blagosklonny M V. STI-571 must select for drug-resistant cells but “no cell breathes fire out of its nostrils like a dragon”. Leukemia. 2002 Apr;16(4):570–2. doi: 10.1038/sj.leu.2402409 11960334
60. Komarova NL, Wodarz D. Drug resistance in cancer: principles of emergence and prevention. Proc Natl Acad Sci U S A. 2005 Jul 5;102(27):9714–9. doi: 10.1073/pnas.0501870102 15980154
61. Chilton-Macneill S, Ho M, Hawkins C, Gassas A, Zielenska M, Baruchel S. C-kit expression and mutational analysis in medulloblastoma. Pediatr Dev Pathol Off J Soc Pediatr Pathol Paediatr Pathol Soc. 2004 Jan;7(5):493–8.
62. Abouantoun TJ, MacDonald TJ. Imatinib blocks migration and invasion of medulloblastoma cells by concurrently inhibiting activation of platelet-derived growth factor receptor and transactivation of epidermal growth factor receptor. Mol Cancer Ther. 2009;8(5):1137–47. doi: 10.1158/1535-7163.MCT-08-0889 19417143
63. Parkkila S, Innocenti A, Kallio H, Hilvo M, Scozzafava A, Supuran CT. The protein tyrosine kinase inhibitors imatinib and nilotinib strongly inhibit several mammalian α-carbonic anhydrase isoforms. Vol. 19, Bioorganic & Medicinal Chemistry Letters. 2009.
64. Davis MI, Hunt JP, Herrgard S, Ciceri P, Wodicka LM, Pallares G, et al. Comprehensive analysis of kinase inhibitor selectivity. Nat Biotechnol. 2011;29.
65. Yang B, Hird AW, Russell DJ, Fauber BP, Dakin LA, Zheng X, et al. Discovery of novel hedgehog antagonists from cell-based screening: Isosteric modification of p38 bisamides as potent inhibitors of SMO. Vol. 22, Bioorganic & Medicinal Chemistry Letters. 2012.
66. Zon LI. Intrinsic and extrinsic control of haematopoietic stem-cell self-renewal. Nature. 2008 May 15;453(7193):306–13. doi: 10.1038/nature07038 18480811
67. Campbell V, Copland M. Hedgehog signaling in cancer stem cells: a focus on hematological cancers. Stem Cells Cloning. 2015;8:27–38. doi: 10.2147/SCCAA.S58613 25691811
68. Kantarjian HM, Giles F, Gattermann N, Bhalla K, Alimena G, Palandri F, et al. Nilotinib (formerly AMN107), a highly selective BCR-ABL tyrosine kinase inhibitor, is effective in patients with Philadelphia chromosome-positive chronic myelogenous leukemia in chronic phase following imatinib resistance and intolerance. Blood. 2007 Nov 15;110(10):3540–6. doi: 10.1182/blood-2007-03-080689 17715389
69. Irvine DA, Zhang B, Kinstrie R, Tarafdar A, Morrison H, Campbell VL, et al. Deregulated hedgehog pathway signaling is inhibited by the smoothened antagonist LDE225 (Sonidegib) in chronic phase chronic myeloid leukaemia. Sci Rep. 2016;6:25476. doi: 10.1038/srep25476 27157927
70. Heikens J, Michiels EMC, Behrendt H, Endert E, Bakker PJM, Fliers E. Long-term neuro-endocrine sequelae after treatment for childhood medulloblastoma. Eur J Cancer. 1998 Sep 1;34(10):1592–7. doi: 10.1016/s0959-8049(98)00212-3 9893634
71. Fossati P, Ricardi U, Orecchia R. Pediatric medulloblastoma: toxicity of current treatment and potential role of protontherapy. Cancer Treat Rev. 2009 Feb;35(1):79–96. doi: 10.1016/j.ctrv.2008.09.002 18976866
72. Reinwald M, Schleyer E, Kiewe P, Blau IW, Burmeister T, Pursche S, et al. Efficacy and pharmacologic data of second-generation tyrosine kinase inhibitor nilotinib in BCR-ABL-positive leukemia patients with central nervous system relapse after allogeneic stem cell transplantation. BioMed Res Int. 2014;2014:15–20.
73. Karuppagounder SS, Brahmachari S, Lee Y, Dawson VL, Dawson TM, Ko HS. The c-Abl inhibitor, nilotinib, protects dopaminergic neurons in a preclinical animal model of Parkinson’s disease. Sci Rep. 2014 Jan;4:4874. doi: 10.1038/srep04874 24786396
74. Hebron ML, Lonskaya I, Moussa CE-H. Nilotinib reverses loss of dopamine neurons and improves motor behavior via autophagic degradation of α-synuclein in Parkinson’s disease models. Hum Mol Genet. 2013 Aug 15;22(16):3315–28. doi: 10.1093/hmg/ddt192 23666528
75. Au K, Singh SK, Burrell K, Sabha N, Hawkins C, Huang A, et al. A preclinical study demonstrating the efficacy of nilotinib in inhibiting the growth of pediatric high-grade glioma. J Neurooncol. 2015 May;122(3):471–80. doi: 10.1007/s11060-015-1744-y 25732621
76. Razis E, Selviaridis P, Labropoulos S, Norris JL, Zhu M-J, Song DD, et al. Phase II Study of Neoadjuvant Imatinib in Glioblastoma: Evaluation of Clinical and Molecular Effects of the Treatment. Clin Cancer Res. 2009 Oct 1;15(19):6258–66. doi: 10.1158/1078-0432.CCR-08-1867 19789313
77. Holdhoff M, Kreuzer K-A, Appelt C, Scholz R, Na I-K, Hildebrandt B, et al. Imatinib mesylate radiosensitizes human glioblastoma cells through inhibition of platelet-derived growth factor receptor. Blood Cells Mol Dis. 2005 Mar;34(2):181–5. doi: 10.1016/j.bcmd.2004.11.006 15727903
78. Abagyan R, Totrov M, Kuznetsov D. ICM-A new method for protein modeling and design: Applications to docking and structure prediction from the distorted native conformation. J Comput Chem. 1994 May;15(5):488–506.
79. Abagyan R, Totrov M. Biased probability Monte Carlo conformational searches and electrostatic calculations for peptides and proteins. J Mol Biol. 1994 Jan 21;235(3):983–1002. doi: 10.1006/jmbi.1994.1052 8289329
80. Totrov M, Abagyan R, editors. Protein-Ligand Docking as an Energy Optimization Problem. In: Drug-Receptor Thermodynamics: Introduction and Applications. John Wiley & Sons Ltd.; 2001. p. 603–24.
81. Schreiber E, Harshman K, Kemler I, Malipiero U, Schaffner W, Fontana A. Astrocytes and glioblastoma cells express novel octamer-DNA binding proteins distinct from the ubiquitous Oct-1 and B cell type Oct-2 proteins. Nucleic Acids Res. 1990 Sep 25;18(18):5495–503. doi: 10.1093/nar/18.18.5495 2216722
82. Kufareva I, Katritch V, Participants of GPCR Dock 2013, Stevens RC, Abagyan R. Advances in GPCR modeling evaluated by the GPCR Dock 2013 assessment: meeting new challenges. Struct Lond Engl 1993. 2014 Aug 5;22(8):1120–39.
83. Wang J, Mook RA, Lu J, Gooden DM, Ribeiro A, Guo A, et al. Identification of a novel Smoothened antagonist that potently suppresses Hedgehog signaling. Bioorg Med Chem. 2012 Nov 15;20(22):6751–7. doi: 10.1016/j.bmc.2012.09.030 23063522
84. Miller-Moslin K, Peukert S, Jain RK, McEwan MA, Karki R, Llamas L, et al. 1-Amino-4-benzylphthalazines as orally bioavailable smoothened antagonists with antitumor activity. J Med Chem. 2009;52(13):3954–3968. doi: 10.1021/jm900309j 19469545
85. Chen JK, Taipale J, Young KE, Maiti T, Beachy PA. Small molecule modulation of Smoothened activity. Proc Natl Acad Sci U S A. 2002 Oct 29;99(22):14071–6. doi: 10.1073/pnas.182542899 12391318
86. Malancona S, Altamura S, Filocamo G, Kinzel O, Hernando JIM, Rowley M, et al. Identification of MK-5710 ((8aS)-8a-methyl-1,3-dioxo-2-[(1S,2R)-2- phenylcyclopropyl]-N-(1-phenyl-1H-pyrazol-5-yl)hexahydroimid azo[1,5-a]pyrazine-7(1H)-carboxamide), a potent smoothened antagonist for use in Hedgehog pathway dependent malignancies, Part. Bioorg Med Chem Lett. 2011;21(15):4422–8. doi: 10.1016/j.bmcl.2011.06.024 21737272
87. Pan S, Wu X, Jiang J, Gao W, Wan Y, Cheng D, et al. Discovery of NVP-LDE225, a Potent and Selective Smoothened Antagonist. ACS Med Chem Lett. 2010 Jun 10;1(3):130–4. doi: 10.1021/ml1000307 24900187
88. Gendreau SB, Hawkins D, Ho C-P, Lewin A, Lin T, Merchant A, et al. Abstract B192: Preclinical characterization of BMS-833923 (XL139), a hedgehog (HH) pathway inhibitor in early clinical development. Mol Cancer Ther. 2009 Dec 10;8(Supplement 1):B192–B192.
89. Peukert S, Jain RK, Geisser A, Sun Y, Zhang R, Bourret A, et al. Identification and structure–activity relationships of ortho-biphenyl carboxamides as potent Smoothened antagonists inhibiting the Hedgehog signaling pathway. Vol. 19, Bioorganic & Medicinal Chemistry Letters. 2009.
90. Kim JJ, Tang JY, Gong R, Kim JJ, Lee JJ, Clemons KV., et al. Itraconazole, a Commonly Used Antifungal that Inhibits Hedgehog Pathway Activity and Cancer Growth. Cancer Cell. 2010 Apr 13;17(4):388–99. doi: 10.1016/j.ccr.2010.02.027 20385363
91. Lee MJ, Hatton BA, Villavicencio EH, Khanna PC, Friedman SD, Ditzler S, et al. Hedgehog pathway inhibitor saridegib (IPI-926) increases lifespan in a mouse medulloblastoma model. Proc Natl Acad Sci U S A. 2012 May 15;109(20):7859–64. doi: 10.1073/pnas.1114718109 22550175
Článok vyšiel v časopise
PLOS One
2019 Číslo 9
- Metamizol jako analgetikum první volby: kdy, pro koho, jak a proč?
- Nejasný stín na plicích – kazuistika
- Masturbační chování žen v ČR − dotazníková studie
- Je Fuchsova endotelová dystrofie rohovky neurodegenerativní onemocnění?
- Fixní kombinace paracetamol/kodein nabízí synergické analgetické účinky
Najčítanejšie v tomto čísle
- Graviola (Annona muricata) attenuates behavioural alterations and testicular oxidative stress induced by streptozotocin in diabetic rats
- CH(II), a cerebroprotein hydrolysate, exhibits potential neuro-protective effect on Alzheimer’s disease
- Comparison between Aptima Assays (Hologic) and the Allplex STI Essential Assay (Seegene) for the diagnosis of Sexually transmitted infections
- Assessment of glucose-6-phosphate dehydrogenase activity using CareStart G6PD rapid diagnostic test and associated genetic variants in Plasmodium vivax malaria endemic setting in Mauritania