Title:
APPLICATIONS OF SPERMIDINE AND ITS DERIVATIVE
Document Type and Number:
WIPO Patent Application WO/2018/192323
Kind Code:
A1
Abstract:
Disclosed are applications of spermidine and its derivative. Based on existing protein structure data and small molecular data, the inventor performs screening by means of software-based computational analysis to obtain compounds that can effectively interfere with PAICS activity. After the compounds are used, the synthesis of SAICAR can be reduced, so that the purpose of treating or mitigating tumors. By using drugs in combination, it is likely to achieve a better effect of treating or mitigating tumors.
Inventors:
ZHU WEI (CN)
PAN WUGUANG (CN)
PAN WUGUANG (CN)
Application Number:
PCT/CN2018/078723
Publication Date:
October 25, 2018
Filing Date:
March 12, 2018
Export Citation:
Assignee:
GENEHEAL BIOTECHNOLOGY CO LTD (CN)
International Classes:
C07D295/13; A61K31/495; A61P35/00
Foreign References:
| CN106399380A | 2017-02-15 | |||
| CN101037423A | 2007-09-19 | |||
| CN104918611A | 2015-09-16 | |||
| CN105246509A | 2016-01-13 |
Other References:
ZHANG, JUN: "Study on the Apoptosis of Hela Cells Induced by Spermidine", MASTER THESIS, 1 April 2013 (2013-04-01), pages 1 - 44, XP009517493
SPIEGEL, E.K.COLMAN, R.F.PATTERSON, D.: "Adenylosuccinate lyase deficiency", MOL GENET METAB, vol. 89, 2006, pages 19 - 31, XP024947111, DOI: 10.1016/j.ymgme.2006.04.018
CLAMADIEU, C.COTTIN, X.ROUSSELLE, C.CLARIS, O.: "Adenylosuccinate lyase deficiency: an unusual cause of neonatal seizure", ARCH PEDIATR, vol. 15, 2008, pages 135 - 138
CASTRO, M.PEREZ-CERDA, C.MERINERO, B.GARCIA, M.J.BERNAR, J.GIL NAGEL, A.TORRES, J.BERMUDEZ, M.GARAVITO, P.MARIE, S. ET AL.: "Screening for adenylosuccinate lyase deficiency: clinical, biochemical and molecular findings in four patients", NEUROPEDIATRICS, vol. 33, 2002, pages 186 - 189
CRISS W E: "A Review of Polyamines and Cancer [J", TURKISH JOURNAL OF MEDICAL SCIENCES, vol. 33, no. 4, 2003, pages 195 - 205
GERNER EWMEYSKENS FL JR.: "Polyamines and cancer: old molecules, new understanding. [J", NAT REV CANCER, vol. 4, no. 10, 2004, pages 781 - 792, XP002556136, DOI: 10.1038/nrc1454
RIAL NSMEYSKENS FLGERNER EW: "Polyamines as mediators of APC-dependent intestinal carcinogenesis and cancer chemoprevention [J", ESSAYS IN BIOCHEMISTRY, vol. 46, no. 1, 2009, pages 111
AMENDOLA RCERVELLI MFRATINI E ET AL.: "Spermine metabolism and anticancer therapy[J", CURRENT CANCER DRUG TARGETS, vol. 9, no. 2, 2009, pages 118 - 130
MANDAL SMANDAL AJOHANSSON H E ET AL.: "Depletion of cellular polyamines, spermidine and spermine, causes a total arrest in translation and growth in mammalian cells [J", PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, vol. 110, no. 6, 2013, pages 2169 - 74
HANAHAN, D.R.A. WEINBERG: "Hallmarks of cancer: the next generation", CELL, vol. 144, no. 5, 2011, pages 646 - 74, XP028185429, DOI: 10.1016/j.cell.2011.02.013
HSU, P.P.D.M. SABATINI: "Cancer cell metabolism: Warburg and beyond", CELL, vol. 134, no. 5, 2008, pages 703 - 7
CHRISTOFK, H.R. ET AL.: "The M2 splice isoform of pyruvate kinase is important for cancer metabolism and tumour growth", NATURE, vol. 452, no. 7184, 2008, pages 230 - 3, XP055009852, DOI: 10.1038/nature06734
WOLF, A. ET AL.: "Hexokinase 2 is a key mediator of aerobic glycolysis and promotes tumor growth in human glioblastoma mult(forme", J EXP MED, vol. 208, no. 2, 2011, pages 313 - 26
CHEN, J. ET AL.: "Shikonin and its analogs inhibit cancer cell glycolysis by targeting tumor pyruvate kinase-M2", ONCOGENE, vol. 30, no. 42, 2011, pages 4297 - 306
ANASTASIOU, D. ET AL.: "Pyruvate kinase M2 activators promote tetramer formation and suppress tumorigenesis", NAT CHEM BIOL, vol. 8, no. 10, 2012, pages 839 - 47, XP055572627, DOI: 10.1038/nchembio.1060
VANDER HEIDEN, M.G.: "Exploiting tumor metabolism: challenges for clinical translation", J CLIN INVEST, vol. 123, no. 9, 2013, pages 3648 - 51
CIARDO, F.C.SALERNOP. CURATOLO: "Neurologic aspects of adenylosuccinate lyase deficiency", J CHILD NEUROL, vol. 16, no. 5, 2001, pages 301 - 8, XP008162221, DOI: 10.1177/088307380101600501
GITIAUX, C. ET AL.: "Misleading behavioural phenotype with adenylosuccinate lyase deficiency", EUR J HUM GENET, vol. 17, no. 1, 2009, pages 133 - 6
MIERZEWSKA, H. ET AL.: "Severe encephalopathy with brain atrophy and hypomyelination due to adenylosuccinate lyase deficiency-MRI, clinical, biochemical and neuropathological findings of Polish patients", FOLIA NEUROPATHOL, vol. 47, no. 4, 2009, pages 314 - 20
EISSMANN, M. ET AL.: "A functional yeast survival screen of tumor-derived cDNA libraries designed to identify anti-apoptotic mammalian oncogenes", PLOS ONE, vol. 8, no. 5, 2013, pages e64873
GOSWAMI, M.T. ET AL.: "Role and regulation of coordinately expressed de novo purine biosynthetic enzymes PP.4Tand PAICS in lung cancer", ONCOTARGET, vol. 6, no. 27, 2015, pages 23445 - 61
CHAKRAVARTHI, B.V ET AL.: "Expression and Role of PAICS, a De Novo Purine Biosynthetic Gene in Prostate Cancer", PROSTATE, vol. 77, no. 1, 2017, pages 10 - 21, XP055448095, DOI: 10.1002/pros.23243
KELLER, K.E.I.S. TANY.S. LEE: "SAICAR stimulates pyruvate kinase isoform M2 and promotes cancer cell survival in glucose-limited conditions", SCIENCE, vol. 338, no. 6110, 2012, pages 1069 - 72
KELLER, K.E. ET AL.: "SAICAR induces protein kinase activity ofPKM2 that is necessary for sustained proliferative signaling of cancer cells", MOL CELL, vol. 53, no. 5, 2014, pages 700 - 9, XP028626420, DOI: 10.1016/j.molcel.2014.02.015
"Pharmaceutical Salts: Properties, Selection and Use", August 2002, HARDCOVER, pages: 388
See also references of EP 3613731A4
SPIEGEL, E.K.COLMAN, R.F.PATTERSON, D.: "Adenylosuccinate lyase deficiency", MOL GENET METAB, vol. 89, 2006, pages 19 - 31, XP024947111, DOI: 10.1016/j.ymgme.2006.04.018
CLAMADIEU, C.COTTIN, X.ROUSSELLE, C.CLARIS, O.: "Adenylosuccinate lyase deficiency: an unusual cause of neonatal seizure", ARCH PEDIATR, vol. 15, 2008, pages 135 - 138
CASTRO, M.PEREZ-CERDA, C.MERINERO, B.GARCIA, M.J.BERNAR, J.GIL NAGEL, A.TORRES, J.BERMUDEZ, M.GARAVITO, P.MARIE, S. ET AL.: "Screening for adenylosuccinate lyase deficiency: clinical, biochemical and molecular findings in four patients", NEUROPEDIATRICS, vol. 33, 2002, pages 186 - 189
CRISS W E: "A Review of Polyamines and Cancer [J", TURKISH JOURNAL OF MEDICAL SCIENCES, vol. 33, no. 4, 2003, pages 195 - 205
GERNER EWMEYSKENS FL JR.: "Polyamines and cancer: old molecules, new understanding. [J", NAT REV CANCER, vol. 4, no. 10, 2004, pages 781 - 792, XP002556136, DOI: 10.1038/nrc1454
RIAL NSMEYSKENS FLGERNER EW: "Polyamines as mediators of APC-dependent intestinal carcinogenesis and cancer chemoprevention [J", ESSAYS IN BIOCHEMISTRY, vol. 46, no. 1, 2009, pages 111
AMENDOLA RCERVELLI MFRATINI E ET AL.: "Spermine metabolism and anticancer therapy[J", CURRENT CANCER DRUG TARGETS, vol. 9, no. 2, 2009, pages 118 - 130
MANDAL SMANDAL AJOHANSSON H E ET AL.: "Depletion of cellular polyamines, spermidine and spermine, causes a total arrest in translation and growth in mammalian cells [J", PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, vol. 110, no. 6, 2013, pages 2169 - 74
HANAHAN, D.R.A. WEINBERG: "Hallmarks of cancer: the next generation", CELL, vol. 144, no. 5, 2011, pages 646 - 74, XP028185429, DOI: 10.1016/j.cell.2011.02.013
HSU, P.P.D.M. SABATINI: "Cancer cell metabolism: Warburg and beyond", CELL, vol. 134, no. 5, 2008, pages 703 - 7
CHRISTOFK, H.R. ET AL.: "The M2 splice isoform of pyruvate kinase is important for cancer metabolism and tumour growth", NATURE, vol. 452, no. 7184, 2008, pages 230 - 3, XP055009852, DOI: 10.1038/nature06734
WOLF, A. ET AL.: "Hexokinase 2 is a key mediator of aerobic glycolysis and promotes tumor growth in human glioblastoma mult(forme", J EXP MED, vol. 208, no. 2, 2011, pages 313 - 26
CHEN, J. ET AL.: "Shikonin and its analogs inhibit cancer cell glycolysis by targeting tumor pyruvate kinase-M2", ONCOGENE, vol. 30, no. 42, 2011, pages 4297 - 306
ANASTASIOU, D. ET AL.: "Pyruvate kinase M2 activators promote tetramer formation and suppress tumorigenesis", NAT CHEM BIOL, vol. 8, no. 10, 2012, pages 839 - 47, XP055572627, DOI: 10.1038/nchembio.1060
VANDER HEIDEN, M.G.: "Exploiting tumor metabolism: challenges for clinical translation", J CLIN INVEST, vol. 123, no. 9, 2013, pages 3648 - 51
CIARDO, F.C.SALERNOP. CURATOLO: "Neurologic aspects of adenylosuccinate lyase deficiency", J CHILD NEUROL, vol. 16, no. 5, 2001, pages 301 - 8, XP008162221, DOI: 10.1177/088307380101600501
GITIAUX, C. ET AL.: "Misleading behavioural phenotype with adenylosuccinate lyase deficiency", EUR J HUM GENET, vol. 17, no. 1, 2009, pages 133 - 6
MIERZEWSKA, H. ET AL.: "Severe encephalopathy with brain atrophy and hypomyelination due to adenylosuccinate lyase deficiency-MRI, clinical, biochemical and neuropathological findings of Polish patients", FOLIA NEUROPATHOL, vol. 47, no. 4, 2009, pages 314 - 20
EISSMANN, M. ET AL.: "A functional yeast survival screen of tumor-derived cDNA libraries designed to identify anti-apoptotic mammalian oncogenes", PLOS ONE, vol. 8, no. 5, 2013, pages e64873
GOSWAMI, M.T. ET AL.: "Role and regulation of coordinately expressed de novo purine biosynthetic enzymes PP.4Tand PAICS in lung cancer", ONCOTARGET, vol. 6, no. 27, 2015, pages 23445 - 61
CHAKRAVARTHI, B.V ET AL.: "Expression and Role of PAICS, a De Novo Purine Biosynthetic Gene in Prostate Cancer", PROSTATE, vol. 77, no. 1, 2017, pages 10 - 21, XP055448095, DOI: 10.1002/pros.23243
KELLER, K.E.I.S. TANY.S. LEE: "SAICAR stimulates pyruvate kinase isoform M2 and promotes cancer cell survival in glucose-limited conditions", SCIENCE, vol. 338, no. 6110, 2012, pages 1069 - 72
KELLER, K.E. ET AL.: "SAICAR induces protein kinase activity ofPKM2 that is necessary for sustained proliferative signaling of cancer cells", MOL CELL, vol. 53, no. 5, 2014, pages 700 - 9, XP028626420, DOI: 10.1016/j.molcel.2014.02.015
"Pharmaceutical Salts: Properties, Selection and Use", August 2002, HARDCOVER, pages: 388
See also references of EP 3613731A4
Attorney, Agent or Firm:
JIAQUAN IP LAW FIRM (CN)
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