Title:
PROTEOLYSIS TARGETING CHIMERA (PROTAC) OF SELECTIVE ANDROGEN RECEPTOR DEGRADER (SARD) COMPOUNDS
Document Type and Number:
WIPO Patent Application WO/2024/010818
Kind Code:
A3
Abstract:
This disclosure is directed to proteolysis targeting chimera (PROTAC) of selective androgen receptor degrader (SARD) compounds which are useful in treating prostate cancer, advanced prostate cancer, castration resistant prostate cancer, triple negative breast cancer, other cancers expressing the androgen receptor, androgenic alopecia or other hyperandrogenic dermal diseases, spinal (and) bulbar muscular atrophy (SBMA), amyotrophic lateral sclerosis (ALS), abdominal aortic aneurysm (AAA), and uterine fibroids, and to methods for reducing the levels of androgen receptor-full length (AR-FL) including pathogenic or resistance mutations, AR-splice variants (AR-SV), and pathogenic polyglutamine (polyQ) polymorphisms of AR in a subject.
Inventors:
NARAYANAN RAMESH (US)
MILLER DUANE D (US)
PONNUSAMY THAMARAI (US)
HE YALI (US)
HWANG DONG-JIN (US)
MILLER DUANE D (US)
PONNUSAMY THAMARAI (US)
HE YALI (US)
HWANG DONG-JIN (US)
Application Number:
PCT/US2023/026943
Publication Date:
March 14, 2024
Filing Date:
July 05, 2023
Export Citation:
Assignee:
UNIV TENNESSEE RES FOUND (US)
International Classes:
A61K47/55; A61K31/4035; A61K31/45; A61K31/454; A61K31/4545
Domestic Patent References:
| WO2021194879A1 | 2021-09-30 | |||
| WO2021231431A1 | 2021-11-18 |
Other References:
XIANG WEIGUO, ZHAO LIJIE, HAN XIN, QIN CHONG, MIAO BUKEYAN, MCEACHERN DONNA, WANG YU, METWALLY HODA, KIRCHHOFF PAUL D., WANG LU, M: "Discovery of ARD-2585 as an Exceptionally Potent and Orally Active PROTAC Degrader of Androgen Receptor for the Treatment of Advanced Prostate Cancer", JOURNAL OF MEDICINAL CHEMISTRY, AMERICAN CHEMICAL SOCIETY, US, vol. 64, no. 18, 23 September 2021 (2021-09-23), US , pages 13487 - 13509, XP055878327, ISSN: 0022-2623, DOI: 10.1021/acs.jmedchem.1c00900
YANG WANG, XUEYANG JIANG, FENG FENG, WENYUAN LIU, HAOPENG SUN: "Degradation of proteins by PROTACs and other strategies", ACTA PHARMACEUTICA SINICA B, vol. 10, no. 2, 1 February 2020 (2020-02-01), pages 207 - 238, XP055767849, ISSN: 2211-3835, DOI: 10.1016/j.apsb.2019.08.001
KREGEL STEVEN, CHAO WANG; XIN HAN; LANBO XIAO; ESTER FERNANDEZ-SALAS; PUSHPINDER BAWA; BROOKE L. MCCOLLUM; KARI WILDER-ROMANS; IN: "Abstract 5679: Androgen receptor degraders overcome common resistance mechanisms developed during prostate cancer treatment", CANCER RESEARCH, AMERICAN ASSOCIATION FOR CANCER RESEARCH, US, vol. 80, no. 16_Suppl., 1 January 2020 (2020-01-01), US, pages 1 - 4, XP093149125, ISSN: 0008-5472
XIN HAN, CHAO WANG, CHONG QIN, WEIGUO XIANG, ESTER FERNANDEZ-SALAS, CHAO-YIE YANG, MI WANG, LIJIE ZHAO, TIANFENG XU, KRISHNAPRIYA : "Discovery of ARD-69 as a Highly Potent Proteolysis Targeting Chimera (PROTAC) Degrader of Androgen Receptor (AR) for the Treatment of Prostate Cancer", JOURNAL OF MEDICINAL CHEMISTRY, AMERICAN CHEMICAL SOCIETY, US, vol. 62, no. 2, 24 January 2019 (2019-01-24), US , pages 941 - 964, XP055658551, ISSN: 0022-2623, DOI: 10.1021/acs.jmedchem.8b01631
YAMASHITA SHINICHI, LAI KUO-PAO, CHUANG KUN-LUNG, XU DEFENG, MIYAMOTO HIROSHI, TOCHIGI TATSUO, PANG SEE-TONG, LI LEI, ARAI YOICHI,: "ASC-J9 Suppresses Castration-Resistant Prostate Cancer Growth through Degradation of Full-length and Splice Variant Androgen Receptors", NEOPLASIA, NEOPLASIA PRESS, US, vol. 14, no. 1, 1 January 2012 (2012-01-01), US , pages 74 - 83, XP093149128, ISSN: 1476-5586, DOI: 10.1593/neo.111436
GIOVANNI L. BERETTA, ZAFFARONI NADIA: "Androgen Receptor-Directed Molecular Conjugates for Targeting Prostate Cancer", FRONTIERS IN CHEMISTRY, vol. 7, no. 369, 28 May 2019 (2019-05-28), pages 1 - 8, XP055761909, DOI: 10.3389/fchem.2019.00369
YANG WANG, XUEYANG JIANG, FENG FENG, WENYUAN LIU, HAOPENG SUN: "Degradation of proteins by PROTACs and other strategies", ACTA PHARMACEUTICA SINICA B, vol. 10, no. 2, 1 February 2020 (2020-02-01), pages 207 - 238, XP055767849, ISSN: 2211-3835, DOI: 10.1016/j.apsb.2019.08.001
KREGEL STEVEN, CHAO WANG; XIN HAN; LANBO XIAO; ESTER FERNANDEZ-SALAS; PUSHPINDER BAWA; BROOKE L. MCCOLLUM; KARI WILDER-ROMANS; IN: "Abstract 5679: Androgen receptor degraders overcome common resistance mechanisms developed during prostate cancer treatment", CANCER RESEARCH, AMERICAN ASSOCIATION FOR CANCER RESEARCH, US, vol. 80, no. 16_Suppl., 1 January 2020 (2020-01-01), US, pages 1 - 4, XP093149125, ISSN: 0008-5472
XIN HAN, CHAO WANG, CHONG QIN, WEIGUO XIANG, ESTER FERNANDEZ-SALAS, CHAO-YIE YANG, MI WANG, LIJIE ZHAO, TIANFENG XU, KRISHNAPRIYA : "Discovery of ARD-69 as a Highly Potent Proteolysis Targeting Chimera (PROTAC) Degrader of Androgen Receptor (AR) for the Treatment of Prostate Cancer", JOURNAL OF MEDICINAL CHEMISTRY, AMERICAN CHEMICAL SOCIETY, US, vol. 62, no. 2, 24 January 2019 (2019-01-24), US , pages 941 - 964, XP055658551, ISSN: 0022-2623, DOI: 10.1021/acs.jmedchem.8b01631
YAMASHITA SHINICHI, LAI KUO-PAO, CHUANG KUN-LUNG, XU DEFENG, MIYAMOTO HIROSHI, TOCHIGI TATSUO, PANG SEE-TONG, LI LEI, ARAI YOICHI,: "ASC-J9 Suppresses Castration-Resistant Prostate Cancer Growth through Degradation of Full-length and Splice Variant Androgen Receptors", NEOPLASIA, NEOPLASIA PRESS, US, vol. 14, no. 1, 1 January 2012 (2012-01-01), US , pages 74 - 83, XP093149128, ISSN: 1476-5586, DOI: 10.1593/neo.111436
GIOVANNI L. BERETTA, ZAFFARONI NADIA: "Androgen Receptor-Directed Molecular Conjugates for Targeting Prostate Cancer", FRONTIERS IN CHEMISTRY, vol. 7, no. 369, 28 May 2019 (2019-05-28), pages 1 - 8, XP055761909, DOI: 10.3389/fchem.2019.00369
Attorney, Agent or Firm:
LOZAN, Vladimir (US)
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