Recent patents for Hedgehog pathway inhibitors for the treatment of malignancy

Bibliography

• Ruiz i Altaba A, Sanchez MP, Dahmane N. Gli and hedgehog in cancer: tumours, embryos and stem cells. Nat Rev Cancer 2002;2:361-72
   PubMed Web of Science ®Google Scholar
• Lum L, Beachy PA. The hedgehog response network: sensors, switches, and routers. Science 2004;304:1755-9
   PubMed Web of Science ®Google Scholar
• Ruiz-Gómez A, Molnar C, Holguín H, et al. The cell biology of Smo signalling and its relationships with GPCRs. Biochim Biophys Acta 2006;1768:901-12
   PubMedGoogle Scholar
• Rubin LL, de Sauvage FJ. Target the hedgehog pathway in cancer. Nat Rev Cancer 2006;5:1026-33
   Google Scholar
• Varjosalo M, Taipale J. Hedgehog: functions and mechanisms. Genes Dev 2008;22:2454-72
   PubMed Web of Science ®Google Scholar
• Chen W, Ren X-R, Nelson CD, et al. Activity-dependent internalization of smoothened mediated by β-Arrestin 2 and GRK2. Science 2004;306:2257-60
   PubMed Web of Science ®Google Scholar
• Corbit KC, Aanstad P, Singla V, et al. Vertebrate smoothened functions at the primary cilium. Nature 2005;437:1018-21
   PubMed Web of Science ®Google Scholar
• Kovacs JJ, Whalen EJ, Liu R, et al. Beta-arrestin-mediated localization of Smoothened to the primary cilium. Science 2008;320:1777-81
   PubMed Web of Science ®Google Scholar
• Rohatgi R, Milenkovic L, Corcoran RB, Scott MP. Hedgehog signal transduction by Smoothened: Pharmacological evidence for a 2-step activation process. Proc Natl Acad Sci USA 2009;106:3196-201
   PubMed Web of Science ®Google Scholar
• di Magliano MP, Hebrok M. Hedgehog signalling in cancer formation and maintenance. Nat Rev Cancer 2003;3:903-11
   PubMed Web of Science ®Google Scholar
• Bale AE, Yu K-P. The hedgehog pathway and basal cell carcinomas. Hum Mol Genet 2001;10:757-62
   PubMed Web of Science ®Google Scholar
• Goodrich LV, Scott MP. Hedgehog and patched in neural development and disease. Neuron 1998;21:1243-57
   PubMed Web of Science ®Google Scholar
• Xie J, Murone M, Luoh S-M, et al. Activating smoothened mutations in sporadic basal-cell carcinoma. Nature 1998;391:90-2
   PubMed Web of Science ®Google Scholar
• Lam CW, Xie J, To KF, et al. A frequent activated smoothened mutation in sporadic basal cell carcinomas. Oncogene 1999;18:833-6
   PubMed Web of Science ®Google Scholar
• Taylor MD, Liu L, Raffel C, et al. Mutations in SUFU predispose to medulloblastoma. Nat Genet 2002;31:306-10
   PubMed Web of Science ®Google Scholar
• Lee Y, Kawagoe R, Sasai K, et al. Loss of suppressor-of-fused function promotes tumorigenesis. Oncogene 2007;26:6442-7
   PubMed Web of Science ®Google Scholar
• Watkins DN, Berman DM, Burkholder SG, et al. Hedgehog signalling within airway epithelial progenitors and in small-cell lung cancer. Nature 2003;422:313-7
   PubMed Web of Science ®Google Scholar
• Yuan Z, Goetz JA, Singh S, et al. Frequent requirement of hedgehog signaling in non-small cell lung carcinoma. Oncogene 2007;26:1046-55
   PubMed Web of Science ®Google Scholar
• Thayer SP, di Magliano MP, Heiser PW, et al. Hedgehog is an early and late mediator of pancreatic cancer tumorigenesis. Nature 2003;425:851-6
   PubMed Web of Science ®Google Scholar
• Karhadkar SS, Bova GS, Abdallah N, et al. Hedgehog signalling in prostate regeneration, neoplasia and metastasis. Nature 2004;431:707-12
   PubMed Web of Science ®Google Scholar
• Berman DM, Karhadkar SS, Maitra A, et al. Widespread requirement for Hedgehog ligand stimulation in growth of digestive tract tumors. Nature 2003;425:846-51
   PubMed Web of Science ®Google Scholar
• Tiet TD, Hopyan S, Nadesan P, et al. Constitutive hedgehog signalling in chondrosarcoma up-regulates tumor cell proliferation. Am J Pathol 2006;168:321-30
   PubMedGoogle Scholar
• Yauch RL, Gould SE, Scales SJ, et al. A paracrine requirement for hedgehog signaling in cancer. Nature 2008;455:406-10
   PubMed Web of Science ®Google Scholar
• Curis, Inc. Hedgehog antagonists, methods and uses related thereto. US20040110663; 2004
   Google Scholar
• Taipale J, Chen JK, Cooper MK, et al. Effects of oncogenic mutations in smoothened and patched can be reversed by cyclopamine. Nature 2000;406:1005-9
   PubMed Web of Science ®Google Scholar
• Frank-Kamenetsky M, Zhang XM, Bottega S, et al. Small-molecule modulators of hedgehog signaling: identification and characterization of smoothened agonists and antagonists. J Biol 2002;1:10.1-.9
   Google Scholar
• Wu X, Walker J, Zhang J, et al. Purmorphamine induces osteogenesis by activation of the hedgehog signaling pathway. Chem Biol 2004;11:1229-38
   PubMedGoogle Scholar
• Dwyer JR, Sever N, Carlson M, et al. Oxysterols are novel activators of the hedgehog signaling pathway in pluripotent mesenchymal cells. J Biol Chem 2007;282:8959-68
   PubMed Web of Science ®Google Scholar
• Nakamura T, Aikawa T, Iwamoto-Enomoto M, et al. Induction of osteogenic differentiation by hedgehog proteins. Biochem Biophys Res Commun 1997;237:465-9
   PubMed Web of Science ®Google Scholar
• Sasai K, Romer JT, Lee Y, et al. Shh pathway activity is down-regulated in cultured medulloblastoma cells: implications for preclinical studies. Cancer Res 2006;66:4215-22
   PubMed Web of Science ®Google Scholar
• Vestergaard J, Pedersen Mikkel W, Pedersen N, et al. Hedgehog signaling in small-cell lung cancer: frequent in vivo but a rare event in vitro. Lung Cancer 2006;52:281-90
   PubMed Web of Science ®Google Scholar
• Curis, Inc. Mediators of hedgehog signaling pathways, compositions and uses related thereto. WO200126644; 2001
   Google Scholar
• Williams JA, Guicherit OM, Zaharian BI, et al. Identification of a small molecule inhibitor of the hedgehog signaling pathway: effects on basal cell carcinoma-like lesions. Proc Natl Acad Sci USA 2003;100:4616-21
   PubMed Web of Science ®Google Scholar
• Available from: http://phx.corporate-ir.net/phoenix.zhtml?c = 123198&p = irol-newsArticle&ID = 881050&highlight
   Google Scholar
• Curis, Inc. Small organic molecule hedgehog agonists as regulators of cell proliferation and differentiation. WO2001019800; 2001
   Google Scholar
• Brunton SA, Stibbard JHA, Rubin LL, et al. Potent inhibitors of the hedgehog signaling pathway. J Med Chem 2008;51:1108-10
   PubMed Web of Science ®Google Scholar
• Curis, Inc. Mediators of hedgehog signaling pathways, compositions, and uses related thereto. WO2003011219; 2003
   Google Scholar
• Curis, Inc. Mediators of hedgehog signaling pathways, compositions, and uses related thereto. WO2006050506; 2006
   Google Scholar
• Romer JT, Kimura H, Magdaleno S, et al. Suppression of the Shh pathway using a small molecule inhibitor eliminates medulloblastoma in Ptc1+/-p53-/- mice. Cancer Cell 2004;6:229-40
   PubMed Web of Science ®Google Scholar
• Johns Hopkins University School of Medicine. Modulators of hedgehog signaling pathways, compositions and uses related thereto. WO2003088970; 2003
   Google Scholar
• The Johns Hopkins University. Hedgehog pathway antagonists. WO2005033288; 2005
   Google Scholar
• Genentech, Inc and Curis Incorporation. Pyridyl inhibitors of hedgehog signaling. WO2006028958; 2006
   Google Scholar
• Available from: http://clinicaltrials.gov/ ct2/results?term = gdc-0449
   Google Scholar
• Marsters JC Jr. Small molecule antagonists of the hedgehog pathway. Annual Meeting of AACR. San Diego; 2008
   Google Scholar
• Genentech, Inc. Quinoxaline inhibitors of the hedgehog signalling pathway. WO2006078283; 2006
   Google Scholar
• Genentech, Inc and Curis Incorporation. Bisamide inhibitors of hedgehog signaling. WO2007059157; 2007
   Google Scholar
• IRM LCC. Compounds and compositions as hedgehog pathway modulators. WO2008014291; 2008
   Google Scholar
• AstraZeneca UK Limited. Heterocyclic amides useful for the treatment of cancer and psoriasis WO2009027746; 2009
   Google Scholar
• Novartis Pharma GmbH. Use of biarylcarboxamides in the treatment of hedgehog pathway-related disorders and their preparation. WO2007120827; 2007
   Google Scholar
• Peukert S, Jain R, Geisser A, et al. Identification and structure-activity relationships of ortho-biphenyl carboxamides as potent smoothened antagonists inhibiting the hedgehog signaling pathway. Bioorg Med Chem Lett 2009;19:328-31
   PubMed Web of Science ®Google Scholar
• IRM LCC. Compounds and compositions as hedgehog pathway modulators. WO2007131201; 2007
   Google Scholar
• IRM LCC. Biphenylcarboxamide derivatives as hedgehog pathway modulators. WO2008154259; 2008
   Google Scholar
• Exelixis, Inc. Inhibitors of the hedgehog pathway. WO2008112913; 2008
   Google Scholar
• Available from: http://clinicaltrial.gov/ct2/show/NCT00670189. A Phase 1 Study of BMS-833923 (XL139) is subjects with advanced of metastatic cancer. February 10, 2009
   Google Scholar
• Pfizer Products, Inc. Benzimidazole derivatives. WO2008075196; 2008
   Google Scholar
• Muller G. Medicinal chemistry of target family directed masterkeys. Drug Discov Today 2003;8:681-91
   PubMed Web of Science ®Google Scholar
• IRM LCC. Compounds and compositions as hedgehog pathway modulators. WO2006050351;2006
   Google Scholar
• Lee J, Wu X, di Magliano MP, et al. A small-molecule antagonist of the hedgehog signaling pathway. ChemBioChem 2007;8:1916-9
   PubMed Web of Science ®Google Scholar
• Cupido T, Rack PG, Firestone AJ, et al. The imidazopyridine derivative JK184 reveals dual roles for microtubules in hedgehog signaling. Angew Chem Int Ed 2009;48:2321-4
   PubMed Web of Science ®Google Scholar
• Licentia OY. Mammalian hedgehog signaling inhibitors. WO2007054623; 2007
   Google Scholar
• Novartis AG. Organic compounds and their uses. WO2008110611; 2008
   Google Scholar
• Amgen, Inc. Phthalazine compounds, compositions and methods of use. WO2009002469; 2009
   Google Scholar
• Actar AB. Hexahydropyrimidine, tetrahydro imidazole or octahydroazepan derivatives. WO2007139492; 2007
   Google Scholar
• Lauth M, Bergstroem A, Shimokawa T, Toftgard R. Inhibition of GLI-mediated transcription and tumor cell growth by small-molecule antagonists. Proc Natl Acad Sci USA 2007;104:8455-60
   PubMed Web of Science ®Google Scholar
• The Regents of The University of California. Targeting GLI proteins in human cancer by small molecules. WO2007067814; 2007
   Google Scholar
• Merck & Co., Inc. Triazole derivatives which are Smo antagonists. WO2008130552; 2008;
   Google Scholar
• Keeler RF. Teratogenic compounds of veratrum californicum (Durand)-IV. First isolation of veratramine and alkaloid Q and a reliable method for isolation of cyclopamine. Phytochemistry 1968;7:303-6
   Web of Science ®Google Scholar
• Keeler RF, Binns W. Teratogenic compounds of veratrum californicum (Durand)-V. Comparison of cyclopian effects of steroidal alkaloids from the plant and structurally related compounds from other sources. Teratology 1968;1:5-10
   PubMedGoogle Scholar
• Incardona JP, Gaffield W, Kapur RP, Roelink H. The teratogenic veratrum alkaloid cyclopamine inhibits sonic hedgehog signal transduction. Development 1998;125:3553-62
   PubMed Web of Science ®Google Scholar
• Cooper MK, Porter JA, Young KE, Beachy PA. Teratogen-mediated inhibition of target tissue response to Shh signaling. Science 1998;280:1603-7
   PubMed Web of Science ®Google Scholar
• Chen JK, Taipale J, Cooper MK, Beachy PA. Inhibition of hedgehog signaling by direct binding of cyclopamine to Smoothened. Genes Dev 2002;16:2743-8
   PubMed Web of Science ®Google Scholar
• Johns Hopkins University School of Medicine. Regulators of the hedgehog pathway, compositions and use related thereto. WO200127135; 2001
   Google Scholar
• Feldmann G, Dhara S, Fendrich V, et al. Blockade of hedgehog signaling inhibits pancreatic cancer invasion and metastases: a new paradigm for combination therapy in solid cancers. Cancer Res 2007;67:2187-96
   PubMed Web of Science ®Google Scholar
• Dahmane N, Sanchez P, Gitton Y, et al. The sonic hedgehog-Gli pathway regulates dorsal brain growth and tumorigenesis. Development 2001;128:5201-12
   PubMed Web of Science ®Google Scholar
• Berman DM, Karhadkar SS, Hallahan AR, et al. Medulloblastoma growth inhibition by hedgehog pathway blockade. Science 2002;297:1559-61
   PubMed Web of Science ®Google Scholar
• Sanchez P, Hernandez AM, Stecca B, et al. Inhibition of prostate cancer proliferation by interference with SONIC HEDGEHOG-GLI1 signaling. Proc Natl Acad Sci USA 2004;101:12561-6
   PubMed Web of Science ®Google Scholar
• Sheng T, Li C, Zhang X, et al. Activation of the hedgehog pathway in advanced prostate cancer. Mol Cancer 2004;3:29-42
   PubMed Web of Science ®Google Scholar
• Clement V, Sanchez P, de Tribolet N, et al. HEDGEHOG-GLI1 signaling regulates human glioma growth, cancer stem cell self-renewal, and tumorigenicity. Curr Biol 2007;17:165-72
   PubMed Web of Science ®Google Scholar
• Stecca B, Mas C, Clement V, et al. Melanomas require HEDGEHOG-GLI signaling regulated by interactions between GLI1 and the RAS-MEK/AKT pathways. Proc Natl Acad Sci USA 2007;104:5895-900
   PubMed Web of Science ®Google Scholar
• Bar EE, Chaudhry A, Lin A, et al. Cyclopamine-mediated hedgehog pathway inhibition depletes stem-like cancer cells in glioblastoma. Stem Cells 2007;25:2524-33
   PubMed Web of Science ®Google Scholar
• Peacock CD, Wang Q, Gesell GS, et al. Hedgehog signaling maintains a tumor stem cell compartment in multiple myeloma. Proc Natl Acad Sci USA 2007;104:4048-53
   PubMed Web of Science ®Google Scholar
• Dierks C, Beigi R, Guo G-R, et al. Expansion of Bcr-Abl-Positive leukemic stem cells is dependent on hedgehog pathway activation. Cancer Cell;14:238-49
   PubMedGoogle Scholar
• Johns Hopkins University School of Medicine. Use of steroidal alkaloid derivatives as inhibitors of hedgehog signaling pathways. WO9952534; 1999
   Google Scholar
• Yeda Research and Development Co., Inc. Use of steroidal alkaloids to reverse multidrug resistance. WO200149279; 2001
   Google Scholar
• Curis, Inc. Regulators of the hedgehog pathway, compositions and uses related thereto. US20040127474; 2004
   Google Scholar
• Izmar. Use of cyclopamine in the treatment of basal cell carcinoma and other tumors. US2004072914; 2004;
   Google Scholar
• The Johns Hopkins University. Use of hedgehog pathway inhibitors in small-cell lung cancer. WO2005042700; 2005
   Google Scholar
• The Johns Hopkins University. Hedgehog protein signaling in prostate regeneration, neoplasia and metastasis. WO2005032343; 2005
   Google Scholar
• The Johns Hopkins University. Elevated hedgehog pathway activity in digestive system tumors, and methods of treating digestive system tumors having elevated hedgehog pathway activity. WO2005013800; 2005;
   Google Scholar
• Medical Research Council, UK. Inhibitor of the SHH signaling pathway and a testosterone suppressing agent for the treatment of cancer. US20060094660; 2006
   Google Scholar
• The University of Chicago, USA. Combination therapy of hedgehog inhibitors, radiation and chemotherapeutic agents. US20070281040; 2006
   Google Scholar
• Infinity Pharmaceuticals, Inc. Dosing regimen for the treatment of cancer. WO2007123511; 2007
   Google Scholar
• Regents of the University of Michigan, USA. Hedgehog signaling pathway antagonist cancer treatment. US2008019961; 2008
   Google Scholar
• Infinity Pharmaceuticals, Inc. Cyclopamine analogues and methods of use thereof. US7407967B2; 2008
   Google Scholar
• Infinity Discovery, Inc. Cyclopamine analogues and methods of use thereof. US7230004B2; 2007
   Google Scholar
• Tremblay MR, Nevalainen M, Nair SJ, et al. Semi-synthetic cyclopamine analogues as potent and orally bioavailable hedgehog pathway antagonists. J Med Chem 2008;51:6646-9
   PubMed Web of Science ®Google Scholar
• Infinity Discovery, Inc. Cyclopamine analogs. WO2008083248; 2008
   Google Scholar
• Infinity Pharmaceuticals, Inc. Heterocyclic cyclopamine analogs and methods of use thereof. WO2008109184; 2008
   Google Scholar
• Infinity Pharmaceuticals, Inc. Cyclopamine lactam analogs and methods of use thereof. WO2008109829; 2008
   Google Scholar
• The Curators of the University of Missouri. Phytoestrogens as regulators of hedgehog signaling and methods of their use in cancer treatment. WO2008131354; 2008
   Google Scholar
• Centre National De La Recherche Scientifique CNRS, Fr. Novel use of mifepristone and derivatives therefor as hedgehog protein signaling pathway modulators and applications of same. WO2004067550; 2004
   Google Scholar
• Genentech, Inc. Antibodies to vertebrate smoothened proteins. US6136958; 2000
   Google Scholar
• Ericson J, Morton S, Kawakami A, et al. Two critical periods of sonic hedgehog signaling required for the specification of motor neuron identity. Cell 1996;87:661-73
   PubMed Web of Science ®Google Scholar
• Genentech, Inc. Using BOC/CDO peptide antagonists as anti-tumor agents. WO2007126455; 2007
   Google Scholar
• Biogen, Inc. Functional antagonists of hedgehog activity. WO200025725; 2000
   Google Scholar
• Government of the United States of America, Represented by the Secretary, Department of Health and Human Services, USA. Smoothened polypeptides and methods of use. WO2008070357; 2008
   Google Scholar
• Remsberg JR, Lou J, Tarasov SG, et al. Structural analogues of smootheneed intracellular loops as potent inhibitors of hedgehog pathway and cancer cell growth. J Med Chem 2007;50:4534-8
   PubMedGoogle Scholar
• Kogerman P, Grimm T, Kogerman L, et al. Mammalian suppressor-of-fused modulates nuclear-cytoplasmic shuttling of GLI-1 Nat Chem. Biol 1999;1:312-9
   Google Scholar
• Karolinska Innovations AB. Peptides consisting of fragments of GLI-1 and SUFUH and their use. WO2001012655; 2001
   Google Scholar
• Isis Pharmaceuticals, Inc. Antisense modulation of sonic hedgehog (SHH) protein expression. US2003105041; 2003
   Google Scholar
• Curis, Inc. RNA interference modulators of hedgehog signaling and uses thereof. US20050256076; 2005
   Google Scholar
• Ruiz i Altaba A, Stecca B. Methods and compositions for inhibiting tumorigenesis US2007009530; 2007
   Google Scholar
• Lawman MJP, Braccili S. Modulating cancer cell characteristics. US2007161588; 2007
   Google Scholar
• Bleicher KH, Green LG, Martin RE, Rogers-Evans M. Ligand identification for G-protein-coupled receptors: a lead generation perspective. Curr Opin Chem Biol 2004;8:287-96
   PubMed Web of Science ®Google Scholar
• Schnur DM, Hermsmeier MA, Tebben AJ. Are target-family-privileged substructures truly privileged? J Med Chem 2006;49:2000-9
   PubMed Web of Science ®Google Scholar
• Stanton BZ, Peng LF, Maloof N, et al. 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
• Arai MA, Tateno C, Hosoya T, et al. Hedgehog/GLI-mediated transcriptional inhibitors from zizyphus cambodiana. Bioorg Med Chem 2008;16:9420-4
   PubMed Web of Science ®Google Scholar