WO2023230770A1 - Procédés de traitement d'adénocarcinome de poumon avec des médicaments ou des composés non anti-luad - Google Patents

Procédés de traitement d'adénocarcinome de poumon avec des médicaments ou des composés non anti-luad Download PDF

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Publication number
WO2023230770A1
WO2023230770A1 PCT/CN2022/096011 CN2022096011W WO2023230770A1 WO 2023230770 A1 WO2023230770 A1 WO 2023230770A1 CN 2022096011 W CN2022096011 W CN 2022096011W WO 2023230770 A1 WO2023230770 A1 WO 2023230770A1
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WO
WIPO (PCT)
Prior art keywords
luad
drug
drugs
compounds
clinical
Prior art date
Application number
PCT/CN2022/096011
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English (en)
Inventor
Jue FAN
Yan Zhang
Jinbo Zhang
Xinpeng HUANG
Jiangning Liu
Nan Fang
Original Assignee
Suzhou Singleron Biotechnologies Co., Ltd.
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Suzhou Singleron Biotechnologies Co., Ltd. filed Critical Suzhou Singleron Biotechnologies Co., Ltd.
Priority to PCT/CN2022/096011 priority Critical patent/WO2023230770A1/fr
Publication of WO2023230770A1 publication Critical patent/WO2023230770A1/fr

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    • 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
    • A61K31/00—Medicinal preparations containing organic active ingredients

Definitions

  • This disclosure generally relates to drug repurposing, and especially a list of identified approved drugs as potential anti-tumor agents against lung adenocarcinoma (LUAD) .
  • LAD lung adenocarcinoma
  • Lung cancer is one of the most frequently diagnosed cancers and the leading cause of cancer-related deaths in the world.
  • LUAD is a form of non-small cell lung cancer (NSCLC) , which is the most common type of lung cancer. NSCLCs account for 80%of lung malignancies, of which 50%are roughly diagnosed as adenocarcinomas.
  • LUAD is usually classified into the following several subtypes: adenocarcinoma in situ (AIS) , minimally invasive adenocarcinoma (MIA) , invasive adenocarcinoma, and variants of adenocarcinoma.
  • AIS adenocarcinoma in situ
  • MIA minimally invasive adenocarcinoma
  • MIA minimally invasive adenocarcinoma
  • variants of adenocarcinoma Despite advances in treatment strategies, the 5-year survival for LUAD patients remains low (approximately 20%) worldwide.
  • a method of treating lung adenocarcinoma can include administering to a subject in need thereof any one or a combination of at least two of drugs or compounds listed in Table 1: methyldopate, guanethidine, diphenylpyraline, tolmetin, nifenazone, Cephalothin, heptaminol, trichlormethiazide, Bucladesine, acetylcholine, imipenem, roxithromycin, butacaine, rivastigmine, ticarcillin, olmesartan, oxolamine, pirenzepine, sulfadimethoxine, tofacitinib, levalbuterol, mecamylamine, meticrane, phenylbutazone, todralazine, tranexamic acid, trimethadione, hydroquinidine, pazuflox
  • the drugs or compounds shown in Table 1 can be administered in a therapeutically effective amount.
  • the therapeutically effective amount is sufficient for inhibiting growth of LUAD cells. In some embodiments, the therapeutically effective amount is sufficient for inhibiting LUAD cell proliferation.
  • the drugs or compounds shown in Table 1 can be administered orally or via injection.
  • the present disclosure provides a method of treating LUAD by administering to a subject in need thereof any one or a combination of at least two of drugs or compounds shown in Table 1, and a convertional anti-LUAD drug (s) .
  • the aforementioned drugs lead to a number of low IC50.
  • the aforementioned drugs reduce the volume of tumor of cell line derived xenografts (CDX) model.
  • the subject is human.
  • the LUAD is NSCLC.
  • the present disclosure provides any one of the drugs listed in Table 1 for use in treating LUAD.
  • the present disclosure further provides use of any one of the drugs listed in Table 1 in treating LUAD.
  • the present disclosure further provides a method for treating LUAD in a clinical patient, comprising administering to the patient a clinically relevant dosage range of a drug or compound listed in Table 1.
  • the drug or compound is administered at a therapeutically effective concentration.
  • the administration of said drug or compound reduces the volume of LUAD tumor in clinical patients.
  • the present disclosure further provides a combination therapy to treat a LUAD patient to control the development of tumor, comprising administering a clinical range of a non-anti-LUAD drug proposed to be repurposed with a conventional anti-LUAD drug to the patient, wherein the combination of said non-anti-LUAD drug and said conventional anti-LUAD drug is administered at a clinically relevant dosage.
  • said non-anti-LUAD drug provides synergy to said conventional anti-LUAD drug.
  • the non-anti-LUAD drug is selected from the group consisting of methyldopate, guanethidine, diphenylpyraline, tolmetin, nifenazone, Cephalothin, heptaminol, trichlormethiazide, Bucladesine, acetylcholine, imipenem, roxithromycin, butacaine, rivastigmine, ticarcillin, olmesartan, oxolamine, pirenzepine, sulfadimethoxine, tofacitinib, levalbuterol, mecamylamine, meticrane, phenylbutazone, todralazine, tranexamic acid, trimethadione, hydroquinidine, pazufloxacin, bretylium, almitrine, chloroprocaine, hydroflumethiazide, deslanoside, Fomepizole, bicyclo
  • the present disclosure further provides a pharmaceutical combination comprising any one or a combination of at least two of the drugs listed in Table 1, and a conventional anti-LUAD drug.
  • the human LUAD cell lines were sourced from commercial vendors. The cancer cells were cultured in RPMI 1640 Medium, supplemented with 10%FBS and 1%penicillin/streptomycin, and were maintained in an incubator at 37 °C and 5%CO 2 . Then the human LUAD cell lines cells were each plated at 5,000 cells per 100 ⁇ l AR-5 medium (ACL4 media with 5%FBS) per well in 96-well plates. For some of screened drugs with definite IC 50 s in public datasets, cells were treated with them in considerate IC 50 s concentrations. Cells were collected on day 0 (control) or after 48 h of treatment. For others, cells per well were treated with those drugs at their indicated doses as a series of concentrations. After three or five days of treatment cells were collected. The cell viability of the samples was used to assess drugs sensitivity.
  • mice Male BALB/c nude mice were housed in a specific pathogen-free facility. In total, 1 ⁇ 10 7 human LUAD cell lines were suspended in PBS and injected subcutaneously into the right flank of each mouse to generate xenograft tumors. When the tumor volume reached an average of ⁇ 100 mm 3 , mice were randomly divided into four groups for each drug: the DMSO group and the drug treated (three different low, medium, and high concentrations of the drug) group; each group had three technical replicate samples. The mice in each group were treated with drug or DMSO through oral gavage or injection. The oral gavage or injection repeated once a day for two weeks. The tumor size (length and width) was measured using a digital caliper every other day to monitor the growth of the tumor. The formula was used to evaluate tumor volume at indicated time points: 1/2 ⁇ L ⁇ W 2 , with L denoting the longest tumor diameter and W is the shortest. Mouse was weighed every other day.

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

Abstract

L'invention concerne un procédé de traitement d'un adénocarcinome de poumon (LUAD), un sous-type de cancer du poumon non à petites cellules (NSCLC). Ce procédé de traitement de LUAD peut comprendre : la fourniture de médicaments ou de composés non anti-LUAD fournis ici à un sujet ayant du LUAD.
PCT/CN2022/096011 2022-05-30 2022-05-30 Procédés de traitement d'adénocarcinome de poumon avec des médicaments ou des composés non anti-luad WO2023230770A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
PCT/CN2022/096011 WO2023230770A1 (fr) 2022-05-30 2022-05-30 Procédés de traitement d'adénocarcinome de poumon avec des médicaments ou des composés non anti-luad

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
PCT/CN2022/096011 WO2023230770A1 (fr) 2022-05-30 2022-05-30 Procédés de traitement d'adénocarcinome de poumon avec des médicaments ou des composés non anti-luad

Publications (1)

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WO2023230770A1 true WO2023230770A1 (fr) 2023-12-07

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PCT/CN2022/096011 WO2023230770A1 (fr) 2022-05-30 2022-05-30 Procédés de traitement d'adénocarcinome de poumon avec des médicaments ou des composés non anti-luad

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Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN104703600A (zh) * 2012-09-07 2015-06-10 埃克塞里艾克西斯公司 用于治疗肺腺癌的met、vegfr和ret的抑制剂
US20160018399A1 (en) * 2013-03-08 2016-01-21 Mayo Foundation For Medical Education And Research Methods and materials for identifying and treating mammals having lung adenocarcinoma characterized by neuroendocrine differentiation
WO2017201142A1 (fr) * 2016-05-17 2017-11-23 Memorial Sloan Kettering Cancer Center Traitement de l'adénocarcinome du poumon
US20190117596A1 (en) * 2016-04-29 2019-04-25 Wayne State University Ty-52156 compounds for the treatment of cancer
US20210023066A1 (en) * 2016-09-20 2021-01-28 Children's Hospital Medical Center Compositions and methods for treatment of cancer
CN113512531A (zh) * 2021-06-04 2021-10-19 广东省实验动物监测所 一种肺腺癌细胞系及其应用

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN104703600A (zh) * 2012-09-07 2015-06-10 埃克塞里艾克西斯公司 用于治疗肺腺癌的met、vegfr和ret的抑制剂
US20160018399A1 (en) * 2013-03-08 2016-01-21 Mayo Foundation For Medical Education And Research Methods and materials for identifying and treating mammals having lung adenocarcinoma characterized by neuroendocrine differentiation
US20190117596A1 (en) * 2016-04-29 2019-04-25 Wayne State University Ty-52156 compounds for the treatment of cancer
WO2017201142A1 (fr) * 2016-05-17 2017-11-23 Memorial Sloan Kettering Cancer Center Traitement de l'adénocarcinome du poumon
US20210023066A1 (en) * 2016-09-20 2021-01-28 Children's Hospital Medical Center Compositions and methods for treatment of cancer
CN113512531A (zh) * 2021-06-04 2021-10-19 广东省实验动物监测所 一种肺腺癌细胞系及其应用

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