Hedgehog pathway inhibitors: a patent review (2009 – present)

Bibliography

• Yang L, Xie G, Fan G, Activation of the hedgehog-signaling pathway in human cancer and the clinical implications. Oncogene 2010;29:469-81
   PubMed Web of Science ®Google Scholar
• Epstein EH. Basal cell carcinoma: attack of the hedgehog. Nat Rev Cancer 2008;8:743-54
   PubMed Web of Science ®Google Scholar
• Berman DM, Karhadkar SS, Hallahan AR, Medulloblastoma growth inhibition by hedgehog pathway blockade. Science 2002;297:1559-61
   PubMed Web of Science ®Google Scholar
• Ling G, Ahmadian A, Persson A, PATCHED and p53 gene alterations in sporadic and hereditary basal cell cancer. Oncogene 2001;20:7770-8
   PubMed Web of Science ®Google Scholar
• Reifenberger J, Wolter M, Knobbe CB, Somatic mutations in the PTCH, SMOH, SUFUH, and TP53 genes in sporadic basal cell carcinomas. Br J Dermatol 2005;152:43-51
   PubMed Web of Science ®Google Scholar
• Klesse LJ, Bowers DC. Childhood medulloblastoma: current status of biology and treatment. CNS Drugs 2010;24:285-301
   PubMedGoogle Scholar
• Pan E, Pellarin M, Holmes E, Isochrome 17q is a negative prognostic factor in poor-risk childhood medulloblastoma patients. Clin Cancer Res 2005;11:4733-40
   PubMed Web of Science ®Google Scholar
• Di Marcotullio L, Ferretti E, De Smaele E, RENKCTD11 is a suppressor of hedgehog signaling and is deleted in human medulloblastoma. Proc Natl Acad Sci 2004;101:10833-8
   PubMed Web of Science ®Google Scholar
• De Smaele E, Di Marcotullio L, Ferretti E, Chromosome 17p deletion in human medulloblastoma: a missing checkpoint in the hedgehog pathway. Cell Cycle 2004;3:1263-6
   PubMedGoogle Scholar
• Tostar U, Malm CJ, Meis-Kindblom JM, Deregulation of the hedgehog signalling pathway: a possible role for the PTCH and SUFU genes in human rhabdomyoma and rhabdomyosarcoma development. J Pathol 2006;208:17-25
   PubMed Web of Science ®Google Scholar
• Thayer SP, di Magliano MP, Heiser PW, Hedgehog is an early and late mediator of pancreatic cancer tumorigenesis. Nature 2003;425:851-6
   PubMed Web of Science ®Google Scholar
• Watkins DN, Berman DM, Burkholder SG, Hedgehog signalling within airway epithelial progenitors and in small-cell lung cancer. Nature 2003;422:313-17
   PubMed Web of Science ®Google Scholar
• Varnat F, Duquet A, Malerba M, Human colon cancer epithelial cells harbor active HEDGEHOG-GLI signalling that is essential for tumour growth, recurrence, metastasis and stem cell survival and expansion. EMBO Mol Med 2009;1:338-51
   PubMed Web of Science ®Google Scholar
• Berman DM, Karhadkar SS, Maitra A, Widespread requirement for hedgehog ligand stimulation in growth of digestive tract tumours. Nature 2003;425:846-51
   PubMed Web of Science ®Google Scholar
• Bhattacharya R, Kwon J, Ali B, Role of hedgehog signaling in ovarian cancer. Clin Cancer Res 2008;14:7659-66
   PubMed Web of Science ®Google Scholar
• Tiet TD, Hopyan S, Nadesan P, Constitutive hedgehog signaling in chondrosarcoma up-regulates tumor cell proliferation. Am J Pathol 2006;168:321-30
   PubMedGoogle Scholar
• Karhadkar SS, Bova GS, Abdallah N, Hedgehog signalling in prostate regeneration, neoplasia and metastasis. Nature 2004;431:707-12
   PubMed Web of Science ®Google Scholar
• Li Y, Maitah MY, Ahmad A, Targeting the hedgehog signalling pathway in cancer therapy. Expert Opin Ther Targets 2012;16:49-66
   PubMed Web of Science ®Google Scholar
• Teglund S, Toftgard R. Hedgehog beyond medulloblastoma and basal cell carcinoma. Biochim Biophys Acta 2010;1805:181-208
   PubMed Web of Science ®Google Scholar
• Merchant AA, Matsui W. Targeting hedgehog – a cancer stem cell pathway. Clin Cancer Res 2010;16:3130-40
   PubMed Web of Science ®Google Scholar
• Ng JM, Curran T. The hedgehog's tale: developing strategies for targeting cancer. Nat Rev Cancer 2011;11:493-501
   PubMed Web of Science ®Google Scholar
• Tremblay MR, Nesler M, Weatherhead R, Castro AC. Recent patents for hedgehog pathway inhibitors for the treatment of malignancy. Expert Opin Ther Patents 2009;19:1039-56
   PubMed Web of Science ®Google Scholar
• A summary of the information that led to the FDA Approval of GDC-0449 (Vismodegib). Available from: http://www.cancer.gov/cancertopics/druginfo/fda-vismodegib
   Google Scholar
• Allison M. Hedgehog hopes lifted by approval and stung by failure. Nat Biotech 2012;30:203
   PubMedGoogle Scholar
• Yauch RL, Dijkgraaf GJP, Alicke B, Smoothened mutation confers resistance to a hedgehog pathway inhibitor in medulloblastoma. Science 2009;326:572-4
   PubMed Web of Science ®Google Scholar
• Dijkgraaf GJP, Alicke B, Weinmann L, Small molecule inhibition of GDC-0449 refractory smoothened mutants and downstream mechanisms of drug resistance. Cancer Res 2011;71:435-44
   PubMed Web of Science ®Google Scholar
• Buonamici S, Williams J, Morrissey M, Interfering with resistance to smoothened antagonists by inhibition of the PI3K pthway in medulloblastoma. Sci Transl Med 2010;2:51ra70
   PubMed Web of Science ®Google Scholar
• Wang J, Lu J, Bond MC, Identification of select glucocorticoids as smoothened agonists: potential utility for regenerative medicine. Proc Natl Acad Sci 2010;107:9323-8
   PubMedGoogle Scholar
• Wang Y, Davidow L, Arvanites AC, Glucocorticoid compounds modify smoothened localization and hedgehog pathway activity. Chem Biol 2012;19:972-82
   PubMed Web of Science ®Google Scholar
• Wu VM, Chen SC, Arkin MR, Small molecule inhibitors of smoothened ciliary localization and ciliogenesis. Proc Natl Acad Sci 2012;109:13644-9
   PubMed Web of Science ®Google Scholar
• The Board of Trustees the Leland Stanford Junior University. Hedgehog pathway antagonists and methods of use. WO2010141680; 2010
   Google Scholar
• Hyman JM, Firestone AJ, Heine VM, Small-molecule inhibitors reveal multiple strategies for hedgehog pathway blockade. Proc Natl Acad Sci 2009;109:14132-7
   Google Scholar
• Stanton BZ, Peng LF, Maloof N, A small molecule that binds hedgehog and blocks its signaling in human cells. Nat Chem Biol 2009;5:154-6
   PubMed Web of Science ®Google Scholar
• Wang Y, Arvanites AC, Davidow L, Selective identification of hedgehog pathway antagonists by direct analysis of smoothened ciliary translocation. ACS Chem Biol 2012;7:1040-8
   PubMed Web of Science ®Google Scholar
• President and Fellows of Harvard College and the General Hospital Corp. Sonic hedgehog modulators. WO2009132032; 2009
   Google Scholar
• Dockendorff C, Nagiec MM, Weiwer M, Macrocyclic hedgehog pathway inhibitors: optimization of cellular activity and mode of action studies. ACS Med Chem Lett 2012;3:808-13
   PubMed Web of Science ®Google Scholar
• Kim W-K, Meliton V, Park KW. Negative regulation of hedgehog signaling by liver X receptors. Mol Endocrinol 2009;23:1532-43
   PubMedGoogle Scholar
• Baranowski M. Biological role of liver X receptors. J Physiol Pharmacol 2008;59(Suppl 7):31-55
   PubMedGoogle Scholar
• The Regeants of the University of California, The Johns Hopkins University. Oxysterols that activate liver X receptor signaling and inhibit hedgehog signaling. WO2011103175; 2011
   Google Scholar
• Pamlico Pharmaceutical, Inc. 2-arylimidazo[1,2-B]pyridazine, 2-phenylimidazo[1,2-A]pyridine, and 1-phenylimidazo[1,2-A]pyrazine derivatives. WO2012088411; 2012
   Google Scholar
• From the Pamlico Pharmaceutical Hedgehog Program Fact Sheet. Available from: http://www.pamlicopharma.com/Home/research
   Google Scholar
• Amgen, Inc. Pyridopyridazine compounds, compositions and methods of use. US20090099173; 2009
   Google Scholar
• Kaizerman JA, Aaron W, An S, Addressing PXR liabilities of phthalazine-based hedgehog/smoothened antagnoists using novel pyridopyridazines. Bioorg Med Chem Lett 2010;20:4607-10
   PubMed Web of Science ®Google Scholar
• Amgen, Inc. Phthalazine compounds, compositions and methods of use. WO2009002469; 2009
   Google Scholar
• Novartis AG. Pyridazine derivatives as Smo inhibitors. WO2010007120; 2010
   Google Scholar
• Novartis AG. Formulations of a pyridazine bipyrazinyl. WO2011130500; 2011
   Google Scholar
• Eli Lilly and Co. Tetrasubstituted pyridazine hedgehog pathway antagonists. WO2010056588; 2010
   Google Scholar
• Eli Lilly and Co. Tetrasubstituted pyridazines hedgehog pathway antagonists. WO2010056620; 2010
   Google Scholar
• Eli Lilly and Co. Disubstituted phthalazine hedgehog pathway antagonists. WO2010147917; 2010
   Google Scholar
• Miller-Moslin K, Peukert S, Jain RK, 1-Amino-4-benzylphthalazines as orally bioavailable smoothened antagonists with antitumor activity. J Med Chem 2009;52:3954-68
   PubMed Web of Science ®Google Scholar
• Bender MH, Hipskind PA, Capen AR, Identification and characterization of a novel smoothened antagonist for the treatment of cancer with deregulated hedgehog signaling [Abstract 2819]. 102nd AACR Meeting 2011;131:E33-44
   Google Scholar
• A description of the clinical trial. Available from: http://www.clinicaltrials.gov/ct2/show/NCT01226485?term=LY2940680&rank=4.
   Google Scholar
• Istituto Di Ricerche Di Biologia Molecolare. 1,2,4-oxadiazole substituted piperidine and piperazine derivatives as Smo antagonists. WO2010013037; 2010
   Google Scholar
• Ontoria JM, Bufi LL, Torrisi C, Identification of a series of 4-[3-quinolin-2-yl)-1,2,4-oxadiazol-5-yl]piperazinyl ureas as potent smoothened antagonist hedgehog pathway inhibitors. Bioorg Med Chem Lett 2011;21:5274-82
   PubMed Web of Science ®Google Scholar
• Muraglia E, Ontoria JM, Branca D, N-(2-alkylaminoethyl)-4-(1,2,4-oxadiazol-5-yl)piperazine-1-carboxamides as highly potent smoothened antagonists. Bioorg Med Chem Lett 2011;21:5283-8
   PubMed Web of Science ®Google Scholar
• Istituto Di Ricerche Di Biologia Molecolare. Piperidine and piperazine derivatives as Smo antagonists. WO2011036478; 2011
   Google Scholar
• Istituto Di Ricerche Di Biologia Molecolare. Saturated bicyclic heterocyclic derivatives as Smo antagonists. WO2010023480; 2010
   Google Scholar
• Istituto Di Ricerche Di Biologia Molecolare. Unsaturated bicyclic heterocyclic derivatives as Smo antagonists. WO2010082044; 2010
   Google Scholar
• Malancona S, Altamura S, Filocamo G, Identification of MK-5710 ((8alphaS)-8alpha-methyl-1,3-dioxo-2-[(1S,2R)-2-phenylcyclopropyl]-N-(1-phenyl-1H-pyrazol-5-yl)hexahydroimidazo[1,5-alpha]pyrazine-7(1H)-carboxamide), a potent smoothened antagonist for use in hedgehog pathway dependent malignancies, part 1. Bioorg Med Chem Lett 2011;21:4422-8
   PubMed Web of Science ®Google Scholar
• Kinzel O, Alfieri A, Altamura S, Identification of MK-5710 ((8alphaS)-8alpha-methyl-1,3-dioxo-2-[(1S,2R)-2-phenylcyclopropyl]-N-(1-phenyl-1H-pyrazol-5-yl)hexahydroimidazo[1,5-alpha]pyrazine-7(1H)-carboxamide), a potent smoothened antagonist for use in hedgehog pathway dependent malignancies, part 2. Bioorg Med Chem Lett 2011;21:4429-35
   PubMed Web of Science ®Google Scholar
• Siena Biotech SPA. Hedgehog pathway antagonists and therapeutic applications thereof. WO2009074300; 2009
   Google Scholar
• Ferruzzi P, Mennillo F, De Rosa A, In vitro and in vivo characterization of a novel hedgehog signaling antagonist in human glioblastoma cell lines. Int J Cancer 2012;131:E33-44
   PubMed Web of Science ®Google Scholar
• Pfizer LLC. Pyridine-2-derivatives as smoothened receptor modulators. WO2012052948; 2012
   Google Scholar
• Rohner A, Spilker ME, Lam JL, Effective targeting of hedgehog signaling in a medulloblastoma model of PF-5274857, a potent and selective smoothened antagonist that penetrates the blood-brain barrier. Mol Cancer Ther 2012;11:57-65
   PubMed Web of Science ®Google Scholar
• Centre National de la Recherche Scientifique. N-acylthiourea and Nacylurea inhibitors of the hedgehog protein signalling pathway. WO2009130422; 2009
   Google Scholar
• Manzetti F, Faure H, Roudaut H, Virtual screening-based discovery and mechanistic characterization of the acylthiourea MRT-10 family of smoothened antagonists. Mol Pharm 2010;78:658-65
   Google Scholar
• Solinas A, Faure H, Roudaut H, Acylthiourea, acylurea, and acylquanidine derivatives with potent hedgehog inhibiting activity. J Med Chem 2012;55:1559-71
   PubMed Web of Science ®Google Scholar
• Centre National de la Recherche Scientifique. Acyl guanidine derivatives modulating the hedgehog protein signaling pathway. WO2011010013; 2011
   Google Scholar
• Takeda Pharmaceutical Co. Ltd. Fused heterocyclic derivative and use thereof. WO2009107850; 2009
   Google Scholar
• Ohashi T, Oguro Y, Tanaka T. Discovery of pyrrolo[3,2-c]quinolone-4-one derivatives as novel hedgehog signaling inhibitors. Bioorg Med Chem 2012; In Press
   Google Scholar
• Ohashi T, Oguro Y, Tanaka T. Discovery of the investigation drug TAK-441, a pyrrolo[3,2-C]pyridine derivative, as a highly potent and orally active hedgehog signaling inhibitor: modification of the core skeleton for improved solubility. Bioorg Med Chem 2012;20:5507-17
   PubMed Web of Science ®Google Scholar
• Biosynergo. Cyclohexylamines, phenylamines and uses thereof. WO2010022159; 2010
   Google Scholar
• Yang H, Xiang J, Wang N, Converse conformational control of smoothened activity by structurally related small molecules. J Biol Chem 2009;284:20876-84
   PubMed Web of Science ®Google Scholar
• Che C, Li S, Yang B, Synthesis and characterization of SANT-75 derivatives as hedgehog-pathway inhibitors. Beilstein J Org Chem 2012;8:841-9
   PubMedGoogle Scholar
• Alla Chem, Inc. Antagonist of smoothened. US20110098291; 2011
   Google Scholar
• Alla Chem LLC. Heterocyclic inhibitors of an HH-signal cascade, medicinal compositions based thereon and methods for treating diseases caused by the aberrant activity of an HH-signal system. US20110053915; 2011
   Google Scholar
• Strand MF, Wilson SR, Dembinski JL, A novel synthetic smoothened antagonist transiently inhibits pancreatic adenocarcinoma xenografts in a mouse model. PLoS One 2011;6:e19904
   PubMedGoogle Scholar
• Curis, Inc. Hedgehog antagonists having zinc binding motifs. WO2012094328; 2012
   Google Scholar
• Chun SG, Zhou W, Yee NS. Combined targeting of histone deacetylases and hedgehog signaling enhances cytotoxicity in pancreatic cancer. Cancer Biol Ther 2009;8:1328-39
   PubMed Web of Science ®Google Scholar
• The Johns Hopkins University, The Board of Trustees of the Leland Stanford Junior University. Compounds for hedgehog pathway blockade in proliferative disorders, including hematopoietic malignancies. WO2009049258; 2009
   Google Scholar
• Kim J, Lee JJ, Kim J. Arsenic antagonizes the hedgehog pathway by preventing ciliary accumulation and reducing stability of the Gli2 transcriptional effector. Proc Natl Acad Sci USA 2010;107:13432-7
   PubMed Web of Science ®Google Scholar
• Beauchamp EM, Ringer L, Bulut G. Arsenic trioxide inhibits human cancer cell growth and tumor development in mice by blocking hedgehog/GLI pathway. J Clin Invest 2011;121:148-60
   PubMed Web of Science ®Google Scholar
• The Wistar Institute and The Trustees of the University of Pennsylvania. Compounds and methods for the prevention and treatment of cancer. WO2012054228;2012
   Google Scholar
• Winkler JD, Isaacs AK, Xiang C, Design, synthesis, and biological evaluation of estrone-derived hedgehog signaling inhibitor. Tetrahedron 2011;67:10261-6
   PubMed Web of Science ®Google Scholar
• Winkler JD, Isaacs A, Holderbaum L, Design and synthesis of inhibitors of hedgehog signaling based on the alkaloid cyclopamine. Org Lett 2009;11:2824-7
   PubMed Web of Science ®Google Scholar
• NovoMedix, LLC. Furanyl compounds and the use thereof. WO2011156321; 2011
   Google Scholar
• Beachy PA, Liu JO. Hedgehog pathway antagonists to treat disease. US20090203713; 2009
   Google Scholar
• Kim J, Tang JY, Gong R, Itraconazole, a commonly used antifungal that inhibits hedgehog pathway activity and cancer growth. Cancer Cell 2010;17:388-99
   PubMed Web of Science ®Google Scholar
• IRM LLC. Hedgehog pathway modulators. WO2010027746; 2010
   Google Scholar
• Uckun FM, Qazi S. Spleen tyrosine kinase as a molecular target for treatment of leukemias and lymphomas. Expert Rev Anticancer Ther 2010;10:1407-18
   PubMed Web of Science ®Google Scholar
• Abraxis Bioscience, LLC. Isoquinoline, quinolone, and quinazoline derivatives as inhibitors of hedgehog signaling. WO2010144586; 2010
   Google Scholar
• Abraxis Bioscience, LLC. Pyridyl-triazine inhibitors of hedgehog signaling. WO2010144404; 2010
   Google Scholar
• Selexagen Therapeutics, Inc. Hedgehog inhibitors. WO2011085128; 2011
   Google Scholar
• Amgen Inc. Oxazole compounds, compositions and methods of use. US20110060011; 2011
   Google Scholar
• Alla Chem, LLC. Imidazo[1,2-A]pyridine-2-yl-phenyl derivatives to be used in cancer treatment. WO2010129620; 2010
   Google Scholar
• Medimmune LLC. Antibodies against sonic hedgehog homolog and uses thereof. WO2010032061; 2010
   Google Scholar
• Goetz SC, Ocbina PJ, Anderson KV. The primary cilium as a hedgehog signal transduction machine. Methods Cell Biol 2009;94:199-222
   PubMed Web of Science ®Google Scholar
• Hassounah NB, Bunch TA, McDermott KM. Molecular pathways: the role of primary cilia in cancer progression and therapeutics with a focus on hedgehog signaling. Clin Cancer Res 2012;18:2429-35
   PubMed Web of Science ®Google Scholar
• Tang JY, Mackay-Wiggan JM, Aszterbaum M, Inhibiting the hedgehog pathway in patients with the basal-cell nevus syndrome. N Engl J Med 2012;366:2180-8
   PubMed Web of Science ®Google Scholar
• Nachtergaele S, Mydock LK, Krishnan K, Oxysterols are allosteric activators of the oncoprotein smoothened. Nat Chem Biol 2012;8:211-20
   PubMed Web of Science ®Google Scholar
• Rominger CM, Tiger Bee W-L, Copeland RA, Evidence for allosteric interactions of antagonist binding the smoothened receptor. J Pharmacol Exp Ther 2009;329:995-1005
   PubMed Web of Science ®Google Scholar