Title:
COMPOSITIONS AND METHODS FOR TREATING CANCER OR PREVENTING, INHIBITING OR REDUCING RISK OF METASTASIS OF A CANCER
Document Type and Number:
WIPO Patent Application WO/2023/133371
Kind Code:
A3
Abstract:
This invention provides compositions of (a) LB-100 or an LB-100 ester, or a pharmaceutically acceptable salt thereof, and (b) a WEE1 kinase inhibitor, checkpoint kinase 1 ("CHK1") inhibitor, B-cell lymphoma-extra large ("BCL-xL") inhibitor, BCL-xL proteolysis-targeting chimera ("BCL‑xL PROTAC"), pan-BCL inhibitor or ataxia telangiectasia and Rad3-related ("ATR") inhibitor. This invention further provides methods for treating cancer or for preventing, inhibiting, or reducing risk of metastasis of a cancer, such as colorectal cancer, cholangiocarcinoma, pancreatic cancer or ovarian cancer, using (a) LB-100 or an LB-100 ester, or a pharmaceutically acceptable salt thereof, and (b) a WEE1 kinase inhibitor, CHK1 inhibitor, BCL-xL inhibitor, BCL‑xL PROTAC, pan-BCL inhibitor or ATR inhibitor.
Inventors:
KOVACH JOHN S (US)
BERNARDS RENE (NL)
DIAS MATHEUS HENRIQUE (NL)
BERNARDS RENE (NL)
DIAS MATHEUS HENRIQUE (NL)
Application Number:
PCT/US2023/060033
Publication Date:
September 07, 2023
Filing Date:
January 03, 2023
Export Citation:
Assignee:
LIXTE BIOTECHNOLOGY INC (US)
STICHTING HET NEDERLANDS KANKER INST ANTONI VAN LEEUWENHOEK ZIEKENHUIS (NL)
STICHTING HET NEDERLANDS KANKER INST ANTONI VAN LEEUWENHOEK ZIEKENHUIS (NL)
International Classes:
A61K31/496; A61K31/497; A61K31/4995
Foreign References:
| US20170136008A1 | 2017-05-18 |
Other References:
SMITH-COHN ET AL.: "Molecularly Targeted Clinical Trials", NEUROSURGERY CLINICS OF NORTH AMERICA, PHILADELPHIA, US, vol. 32, no. 2, 18 February 2021 (2021-02-18), US , pages 191 - 210, XP009548724, ISSN: 1042-3680
YANG SHIH-HUNG, KUO TING-CHUN, WU HSU, GUO JHE-CYUAN, HSU CHIUN, HSU CHIH-HUNG, TIEN YU-WEN, YEH KUN-HUEI, CHENG ANN-LII, KUO SUNG: "Perspectives on the combination of radiotherapy and targeted therapy with DNA repair inhibitors in the treatment of pancreatic cancer", WORLD JOURNAL OF GASTROENTEROLOGY, WJG PRESS, CN, vol. 22, no. 32, 28 August 2016 (2016-08-28), CN , pages 7275, XP093091095, ISSN: 1007-9327, DOI: 10.3748/wjg.v22.i32.7275
MAZHAR SAHAR, TAYLOR SARAH E., SANGODKAR JAYA, NARLA GOUTHAM: "Targeting PP2A in cancer: Combination therapies", BIOCHIMICA ET BIOPHYSICA ACTA, ELSEVIER SCIENCE PUBLISHERS, AMSTERDAM., NL, vol. 1866, no. 1, 1 January 2019 (2019-01-01), NL , pages 51 - 63, XP093091100, ISSN: 0167-4889, DOI: 10.1016/j.bbamcr.2018.08.020
LI FENG; KOZONO DAVID; DERASKA PETER; BRANIGAN TIMOTHY; DUNN CONNOR; ZHENG XIAO-FENG; PARMAR KALINDI; NGUYEN HUY; DECAPRIO JAMES; : "CHK1 Inhibitor Blocks Phosphorylation of FAM122A and Promotes Replication Stress", MOLECULAR CELL, ELSEVIER, AMSTERDAM, NL, vol. 80, no. 3, 26 October 2020 (2020-10-26), AMSTERDAM, NL, pages 410, XP086318800, ISSN: 1097-2765, DOI: 10.1016/j.molcel.2020.10.008
DIAS MATHEUS HENRIQUE, FRISKES ANOEK, WANG SIYING, FERNANDES NETO JOAO M., VAN GEMERT FRANK, MOURRAGUI SOUFIANE, KUIKEN HENDRIK J.: "Paradoxical activation of oncogenic signaling as a cancer treatment strategy", BIORXIV, 7 February 2023 (2023-02-07), XP093091106, Retrieved from the Internet [retrieved on 20231012], DOI: 10.1101/2023.02.06.527335
YANG SHIH-HUNG, KUO TING-CHUN, WU HSU, GUO JHE-CYUAN, HSU CHIUN, HSU CHIH-HUNG, TIEN YU-WEN, YEH KUN-HUEI, CHENG ANN-LII, KUO SUNG: "Perspectives on the combination of radiotherapy and targeted therapy with DNA repair inhibitors in the treatment of pancreatic cancer", WORLD JOURNAL OF GASTROENTEROLOGY, WJG PRESS, CN, vol. 22, no. 32, 28 August 2016 (2016-08-28), CN , pages 7275, XP093091095, ISSN: 1007-9327, DOI: 10.3748/wjg.v22.i32.7275
MAZHAR SAHAR, TAYLOR SARAH E., SANGODKAR JAYA, NARLA GOUTHAM: "Targeting PP2A in cancer: Combination therapies", BIOCHIMICA ET BIOPHYSICA ACTA, ELSEVIER SCIENCE PUBLISHERS, AMSTERDAM., NL, vol. 1866, no. 1, 1 January 2019 (2019-01-01), NL , pages 51 - 63, XP093091100, ISSN: 0167-4889, DOI: 10.1016/j.bbamcr.2018.08.020
LI FENG; KOZONO DAVID; DERASKA PETER; BRANIGAN TIMOTHY; DUNN CONNOR; ZHENG XIAO-FENG; PARMAR KALINDI; NGUYEN HUY; DECAPRIO JAMES; : "CHK1 Inhibitor Blocks Phosphorylation of FAM122A and Promotes Replication Stress", MOLECULAR CELL, ELSEVIER, AMSTERDAM, NL, vol. 80, no. 3, 26 October 2020 (2020-10-26), AMSTERDAM, NL, pages 410, XP086318800, ISSN: 1097-2765, DOI: 10.1016/j.molcel.2020.10.008
DIAS MATHEUS HENRIQUE, FRISKES ANOEK, WANG SIYING, FERNANDES NETO JOAO M., VAN GEMERT FRANK, MOURRAGUI SOUFIANE, KUIKEN HENDRIK J.: "Paradoxical activation of oncogenic signaling as a cancer treatment strategy", BIORXIV, 7 February 2023 (2023-02-07), XP093091106, Retrieved from the Internet
Attorney, Agent or Firm:
LANGER, Matthew E. et al. (US)
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