Title:
POLYPEPTIDE INHIBITORS OF LACTATE DEHYDROGENASE ACTIVITY FOR USE IN CANCER THERAPY
Document Type and Number:
WIPO Patent Application WO/2022/162233
Kind Code:
A3
Abstract:
The present invention relates to a polypeptide comprising the amino acid sequence of formula (I): GX1MMX2LQHGSX3X4X5QTP. These polypeptides modulate the activity the native tetrameric lactate dehydrogenase LDH-1, by inhibiting the tetramerization of its subunits. The invention also relates to the therapeutic use of these polypeptides as a medicament, in particular for the prevention and/or the treatment of cancer.
Inventors:
SONVEAUX PIERRE (BE)
FREDERICK RAPHAËL (BE)
THABAULT LÉOPOLD (GB)
LIBERELLE MAXIME (FR)
FREDERICK RAPHAËL (BE)
THABAULT LÉOPOLD (GB)
LIBERELLE MAXIME (FR)
Application Number:
PCT/EP2022/052282
Publication Date:
November 10, 2022
Filing Date:
February 01, 2022
Export Citation:
Assignee:
UNIV CATHOLIQUE LOUVAIN (BE)
International Classes:
C12N9/04; A61K38/44; C07K7/00
Domestic Patent References:
| WO2020221899A1 | 2020-11-05 | |||
| WO2000055350A1 | 2000-09-21 |
Foreign References:
| US6444425B1 | 2002-09-03 |
Other References:
THABAULT LÉOPOLD ET AL: "Interrogating the Lactate Dehydrogenase Tetramerization Site Using (Stapled) Peptides", vol. 63, no. 9, 14 May 2020 (2020-05-14), US, pages 4628 - 4643, XP055813962, ISSN: 0022-2623, Retrieved from the Internet [retrieved on 20210618], DOI: 10.1021/acs.jmedchem.9b01955
FARZANEH JAFARY ET AL: "Novel Peptide Inhibitors for Lactate Dehydrogenase A (LDHA): A Survey to Inhibit LDHA Activity via Disruption of Protein-Protein Interaction", SCIENTIFIC REPORTS, vol. 9, no. 1, 18 March 2019 (2019-03-18), pages 4686, XP055624255, DOI: 10.1038/s41598-019-38854-7
FRIBERG ANDERS ET AL: "Structural Evidence for Isoform-Selective Allosteric Inhibition of Lactate Dehydrogenase A", vol. 5, no. 22, 9 June 2020 (2020-06-09), US, pages 13034 - 13041, XP055814265, ISSN: 2470-1343, Retrieved from the Internet [retrieved on 20210621], DOI: 10.1021/acsomega.0c00715
DATABASE Geneseq [online] 3 February 2011 (2011-02-03), HOOD L. ET AL: "Human organ specific protein related amino acid sequence SEQ:51834.", XP055814275, retrieved from EBI accession no. GSP:AUN50493 Database accession no. AUN50493
DATABASE Geneseq [online] 7 October 2002 (2002-10-07), "Human ADPI tryptic digest peptide #243.", XP055814278, retrieved from EBI accession no. GSP:ABG67534 Database accession no. ABG67534
FIUME LUIGI ET AL: "Inhibition of lactate dehydrogenase activity as an approach to cancer therapy", vol. 6, no. 4, 1 March 2014 (2014-03-01), GB, pages 429 - 445, XP055815696, ISSN: 1756-8919, Retrieved from the Internet [retrieved on 20210220], DOI: 10.4155/fmc.13.206
THABAULT LÉOPOLD ET AL: "Discovery of a novel lactate dehydrogenase tetramerization domain using epitope mapping and peptides", JOURNAL OF BIOLOGICAL CHEMISTRY, vol. 296, 17 February 2021 (2021-02-17), US, pages 100422, XP055815720, ISSN: 0021-9258, DOI: 10.1016/j.jbc.2021.100422
DATABASE Genbank [online] 1 September 2003 (2003-09-01), TAKAFUJI V A ET AL: "Equus caballus lactate dehydrogenase B(LDHB) mRNA partial cds", XP055959521, retrieved from EBI Database accession no. AY246702
DATABASE Genbank [online] 1 September 2003 (2003-09-01), TAKAFUJI V A ET AL: "Equus caballus lactate dehydrogenase B(LDHB) mRNA partial cds", XP055959521, retrieved from EBI Database accession no. AY246702
FARZANEH JAFARY ET AL: "Novel Peptide Inhibitors for Lactate Dehydrogenase A (LDHA): A Survey to Inhibit LDHA Activity via Disruption of Protein-Protein Interaction", SCIENTIFIC REPORTS, vol. 9, no. 1, 18 March 2019 (2019-03-18), pages 4686, XP055624255, DOI: 10.1038/s41598-019-38854-7
FRIBERG ANDERS ET AL: "Structural Evidence for Isoform-Selective Allosteric Inhibition of Lactate Dehydrogenase A", vol. 5, no. 22, 9 June 2020 (2020-06-09), US, pages 13034 - 13041, XP055814265, ISSN: 2470-1343, Retrieved from the Internet
DATABASE Geneseq [online] 3 February 2011 (2011-02-03), HOOD L. ET AL: "Human organ specific protein related amino acid sequence SEQ:51834.", XP055814275, retrieved from EBI accession no. GSP:AUN50493 Database accession no. AUN50493
DATABASE Geneseq [online] 7 October 2002 (2002-10-07), "Human ADPI tryptic digest peptide #243.", XP055814278, retrieved from EBI accession no. GSP:ABG67534 Database accession no. ABG67534
FIUME LUIGI ET AL: "Inhibition of lactate dehydrogenase activity as an approach to cancer therapy", vol. 6, no. 4, 1 March 2014 (2014-03-01), GB, pages 429 - 445, XP055815696, ISSN: 1756-8919, Retrieved from the Internet
THABAULT LÉOPOLD ET AL: "Discovery of a novel lactate dehydrogenase tetramerization domain using epitope mapping and peptides", JOURNAL OF BIOLOGICAL CHEMISTRY, vol. 296, 17 February 2021 (2021-02-17), US, pages 100422, XP055815720, ISSN: 0021-9258, DOI: 10.1016/j.jbc.2021.100422
DATABASE Genbank [online] 1 September 2003 (2003-09-01), TAKAFUJI V A ET AL: "Equus caballus lactate dehydrogenase B(LDHB) mRNA partial cds", XP055959521, retrieved from EBI Database accession no. AY246702
DATABASE Genbank [online] 1 September 2003 (2003-09-01), TAKAFUJI V A ET AL: "Equus caballus lactate dehydrogenase B(LDHB) mRNA partial cds", XP055959521, retrieved from EBI Database accession no. AY246702
Attorney, Agent or Firm:
ICOSA (FR)
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