WO2022192182A3 - USES OF GLUCOCORTICOID RECEPTOR (GR) ANTAGONIST, ANTIANDROGEN, AND AKT INHIBITOR/PI3K INHIBITOR/mTOR INHIBITOR COMBINATIONS - Google Patents

USES OF GLUCOCORTICOID RECEPTOR (GR) ANTAGONIST, ANTIANDROGEN, AND AKT INHIBITOR/PI3K INHIBITOR/mTOR INHIBITOR COMBINATIONS Download PDF

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Publication number
WO2022192182A3
WO2022192182A3 PCT/US2022/019246 US2022019246W WO2022192182A3 WO 2022192182 A3 WO2022192182 A3 WO 2022192182A3 US 2022019246 W US2022019246 W US 2022019246W WO 2022192182 A3 WO2022192182 A3 WO 2022192182A3
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WO
WIPO (PCT)
Prior art keywords
inhibitor
antiandrogen
antagonist
glucocorticoid receptor
akt
Prior art date
Application number
PCT/US2022/019246
Other languages
French (fr)
Other versions
WO2022192182A2 (en
Inventor
Shravani Barkund
Haiying Zhou
Lori S. Friedman
Anneleen Daemen
Original Assignee
Oric Pharmaceuticals, Inc.
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Publication date
Application filed by Oric Pharmaceuticals, Inc. filed Critical Oric Pharmaceuticals, Inc.
Publication of WO2022192182A2 publication Critical patent/WO2022192182A2/en
Publication of WO2022192182A3 publication Critical patent/WO2022192182A3/en

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
    • A61K31/565—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol
    • A61K31/567—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol substituted in position 17 alpha, e.g. mestranol, norethandrolone
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/4164—1,3-Diazoles
    • A61K31/4166—1,3-Diazoles having oxo groups directly attached to the heterocyclic ring, e.g. phenytoin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/4353—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems
    • A61K31/4375—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a six-membered ring having nitrogen as a ring heteroatom, e.g. quinolizines, naphthyridines, berberine, vincamine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/517—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
    • A61K31/565—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol
    • A61K31/568—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol substituted in positions 10 and 13 by a chain having at least one carbon atom, e.g. androstanes, e.g. testosterone
    • A61K31/569—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol substituted in positions 10 and 13 by a chain having at least one carbon atom, e.g. androstanes, e.g. testosterone substituted in position 17 alpha, e.g. ethisterone
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
    • A61K31/57—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone
    • A61K31/573—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2300/00—Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00

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  • Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Epidemiology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

Disclosed herein are methods of treating prostate cancer in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of (i) a glucocorticoid receptor (GR) antagonist and (ii) an antiandrogen, and (iii) a third agent, wherein the third agent is selected from one or more of an AKT inhibitor, a PI3K inhibitor, or an mTOR inhibitor.
PCT/US2022/019246 2021-03-09 2022-03-08 USES OF GLUCOCORTICOID RECEPTOR (GR) ANTAGONIST, ANTIANDROGEN, AND AKT INHIBITOR/PI3K INHIBITOR/mTOR INHIBITOR COMBINATIONS WO2022192182A2 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US202163158778P 2021-03-09 2021-03-09
US63/158,778 2021-03-09

Publications (2)

Publication Number Publication Date
WO2022192182A2 WO2022192182A2 (en) 2022-09-15
WO2022192182A3 true WO2022192182A3 (en) 2022-10-20

Family

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PCT/US2022/019246 WO2022192182A2 (en) 2021-03-09 2022-03-08 USES OF GLUCOCORTICOID RECEPTOR (GR) ANTAGONIST, ANTIANDROGEN, AND AKT INHIBITOR/PI3K INHIBITOR/mTOR INHIBITOR COMBINATIONS

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WO (1) WO2022192182A2 (en)

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20240091218A1 (en) * 2022-09-02 2024-03-21 Corcept Therapeutics Incorporated Methods of treating prostate cancer using exicorilant and enzalutamide

Non-Patent Citations (9)

* Cited by examiner, † Cited by third party
Title
ADELAIYE-OGALA REMI M., GRYDER BERKLEY, NGUYEN YEN THI MINH, ALILIN AIAN NEIL, GRAYSON ADLAI, JANSSON KEITH H., BESHIRI MICHAEL L.: "Targeting the PI3K/AKT pathway overcomes enzalutamide resistance by inhibiting induction of the glucocorticoid receptor", MOLECULAR CANCER THERAPEUTICS, vol. 19, no. 7, 1 July 2020 (2020-07-01), XP093000087, DOI: 10.1101/783803 *
BARKUND SHRAVANI, ZHOU HAIYING, FRIEDMAN LORI S, DAEMEN ANNELEEN: "GR Antagonist ORIC-101 Overcomes GR-mediated Resistance to the Combination of AR and AKT Inhibition in Preclinical Prostate Cancer Cell Lines", AACR VIRTUAL ANNUAL MEETING, 10 April 2021 (2021-04-10), XP093000108 *
HELEN CHOW; PARAMITA M. GHOSH; RALPH DEVERE WHITE; CHRISTOPHER P. EVANS; MARC A. DALL'ERA; STANLEY A. YAP; YUEJU LI; LAUREL A: "A phase 2 clinical trial of everolimus plus bicalutamide for castration‐resistant prostate cancer", CANCER, AMERICAN CANCER SOCIETY , PHILADELPHIA , PA, US, vol. 122, no. 12, 28 March 2016 (2016-03-28), US , pages 1897 - 1904, XP071036653, ISSN: 0008-543X, DOI: 10.1002/cncr.29927 *
KOLINSKY M.P., RESCIGNO P., BIANCHINI D., ZAFEIRIOU Z., MEHRA N., MATEO J., MICHALAREA V., RIISNAES R., CRESPO M., FIGUEIREDO I., : "A phase I dose-escalation study of enzalutamide in combination with the AKT inhibitor AZD5363 (capivasertib) in patients with metastatic castration-resistant prostate cancer", ANNALS OF ONCOLOGY, KLUWER DORDRECHT, NL, vol. 31, no. 5, 21 February 2020 (2020-02-21), NL , pages 619 - 625, XP093000075, ISSN: 0923-7534, DOI: 10.1016/j.annonc.2020.01.074 *
NANNINI, M. A. ET AL.: "GDC-0068, A Novel and Selective Akt Inhibitor Demonstrates Improvement in Anti-tumor Activity When Combined with Androgen Receptor Pathway Antagonists, MDV3100 and Abiraterone, in Prostate Cancer Models", EUROPEAN JOURNAL OF CANCER, vol. 48, no. 6, 2012, pages 112 - 113, XP055654797, DOI: 10.1016/S0959-8049(12)72166-4 *
NEAL D. SHORE, ELENI EFSTATHIOU, RUPAL PATEL, RONGDA XU, ANN JOHNSON, PRATIK S. MULTANI: "An open-label phase lb study of ORIC-101 in combination with enzalutamide in patients with metastatic prostate cancer progressing on enzalutamide", JOURNAL OF CLINICAL ONCOLOGY, vol. 38, no. 6, 30 November 2019 (2019-11-30), USA , pages 1 - 2, XP009540735, ISSN: 1527-7755 *
SQUILLACE RACHEL M., MILLER DAVID, WARDWELL SCOTT D., WANG FRANK, CLACKSON TIM, RIVERA VICTOR M.: "Synergistic activity of the mTOR inhibitor ridaforolimus and the antiandrogen bicalutamide in prostate cancer models", INTERNATIONAL JOURNAL OF ONCOLOGY, DEMETRIOS A. SPANDIDOS ED. & PUB, GR, vol. 41, no. 2, 1 August 2012 (2012-08-01), GR , pages 425 - 432, XP093000093, ISSN: 1019-6439, DOI: 10.3892/ijo.2012.1487 *
TOREN, P. ET AL.: "Combination AZD5363 with Enzalutamide Significantly Delays Enzalutamide-resistant Prostate Cancer in Preclinical Models", EUROPEAN UROLOGY, vol. 67, no. 6, 2015, pages 986 - 990, XP055505771, DOI: 10.1016/j.eururo.2014.08.006 *
ZHOU H., ET AL.: "ORIC-101 Overcomes Glucocorticoid-Driven Resistance to Androgen Receptor Inhibition in CRPC BACKGROUND", PROCEEDINGS OF THE AACR-NCIEORTC INTERNATIONAL CONFERENCE ON MOLECULAR TARGETS AND CANCER THERAPEUTICS, BOSTON, MA. PHILADELPHIA (PA), 26 October 2019 (2019-10-26), Boston, MA. Philadelphia (PA), XP093000064 *

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