Multiple sclerosis (MS) is the most frequently acquired demyelinating disease and the first cause of non-traumatic chronic disability in young adults. Major progress has been achieved in the treatment of MS through the development of therapies targeting the adaptative immune system, which drastically reduce the relapse rate, with various efficiency and safety profiles (Ontaneda, 2015). However, these drugs generally fail to prevent disability worsening along the disease course, and we are now assisting to a shift in therapeutic objectives from the development of new immune drugs towards the identification of therapeutic strategies that could prevent neurodegeneration by promoting myelin regeneration (Stangel, 2017; Stankoff, 2016), in order to prevent neurological disability in MS (Irvine and Blakemore, 2008; Patrikios, 2006; Duncan I, 2017, Bodini, 2016).
Among the first candidate compounds developed to promote remyelination was the anti Lingo1 antibody, which enhance remyelination (Mi, 2009). Medium and large throughput screening of drug libraries subsequently identified several chemical classes of compounds with strong promyelinating properties, such as the antifongic drug miconazole (Najm, 2015) or the muscarinic antagonist clemastine (Wei, 2014). A recent innovative trial has investigated the effect of clemastine, compared to placebo, in a small sample of subjects (25 patients per group) and showed that clemastine could significantly improve the optic nerve conduction speed which reflecting myelin integrity and functionality (Green, 2017).
Our preclinical research has allowed us to identify ifenprodil as a powerful drug to promote myelin repair in vitro and in vivo across species. In parallel our team recently pioneered and optimized a PET imaging approach for quantifying remyelination in the whole brain, that allowed to enhance the sensitivity to detect the myelin repair process, and showed that patients are characterized by heterogeneous profiles of spontaneous remyelination profiles that are closely linked to disability accrual (Bodini, 2016).

开始日期2024-03-01

申办/合作机构

Assistance Publique des Hôpitaux de Paris SA

KCT0005307

/ Recruiting临床2期IIT

AN OPEN LABEL PHYSICIAN INITIATED 28 DAY PHASE 2A STUDY OF IFENPRODIL ON LUNG FUNCTION IN CONFIRMED COVID-19 INFECTED PATIENTS WITH SEVERE PNEUMONIA

开始日期2020-09-30

申办/合作机构

Dong-A University Hospital

100 项与酒石酸艾芬地尔相关的临床结果

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100 项与酒石酸艾芬地尔相关的转化医学

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100 项与酒石酸艾芬地尔相关的专利（医药）

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1,413

项与酒石酸艾芬地尔相关的文献（医药）

2025-03-01·BIOORGANIC & MEDICINAL CHEMISTRY

Design, synthesis, and evaluation of the pharmacological activity of novel NMDA receptor antagonists based on the germacrone scaffold

Article

作者: Wang, Shi ; Cheng, Maosheng ; Ma, Chao ; Shi, Chaohui ; Fang, Fang ; Xu, Yang ; Zhang, Yue ; Zhang, Yuanhu ; Song, Pengfei ; Mao, Qingqiu ; Xu, Lang ; Huang, Xian

The NMDA receptor has long attracted researchers' attention due to its potential as a drug target and its central role in the central nervous system. The NMDA receptor is a ligand-gated and voltage-dependent ion channel widely distributed in the central nervous system. In this study, we employed a drug design strategy combining "molecular assembly" and "combinatorial chemistry." By reducing the carbonyl group of germacrone to a hydroxyl group and esterifying it with alanine and linarinic acid, we successfully obtained nine novel germacrone derivatives through two rounds of structural optimization. We evaluated the neuroprotective activity of these nine derivatives using the MTT assay. The results revealed that compound C1 exhibited particularly outstanding activity, achieving a cell protection rate of 29.63 ± 1.56 % at a concentration of 0.05 μM, outperforming the positive control drug, ifenprodil. Further experiments on NMDA-induced Ca²⁺ influx verified that the action site of compound C1 was the NMDA receptor, and demonstrated its superior antagonistic effect on the NMDA receptor compared to germacrone and ifenprodil. Additionally, molecular docking studies and ADMET property predictions were conducted for compound C1. The results showed that compound C1 tightly bound to the active site of the NMDA receptor and possessed favorable pharmacokinetic properties. In conclusion, compound C1, characterized by a germacrone-linarinic acid structure, not only exhibits strong antagonistic effects on the NMDA receptor but also demonstrates excellent pharmacokinetic properties, indicating its potential for further development as a therapeutic drug for central nervous system diseases.

2024-11-14·JOURNAL OF MEDICINAL CHEMISTRY

Enantiomerically Pure Indazole Bioisosteres of Ifenprodil and Ro 25-6981 as Negative Allosteric Modulators of NMDA Receptors with the GluN2B Subunit

Article

作者: Wünsch, Bernhard ; Goerges, Gunnar ; Seebohm, Guiscard ; Schmidt, Judith ; Schreiber, Julian A. ; Schepmann, Dirk ; Frehland, Bastian ; Lüken, Judith

Administration of negative allosteric modulators of GluN2B subunit-containing NMDA receptors such as Ro 25-6981 (1) and ifenprodil (2) results in neuroprotective effects. In this study, the phenol of 1 and 2 was replaced bioisosterically by an indazole to inhibit glucuronidation. The γ- and β-aminoalcohols 10 and 11 were prepared without installing a protective group at the indazole ring using the ketone 6 as a common intermediate. All four stereoisomeric γ- and β-aminoalcohols 10 and 11 were obtained by diastereoselective reduction of ketones 7 and 9 followed by separation of enantiomers. The analogously structured γ-aminoalcohol (1S,2S)-10c (Ro 25-6981 bioisostere) and β-aminoalcohol (1R,2R)-11c (ifenprodil bioisostere) exhibited high GluN2B affinity (K_i = 50 and 66 nM, respectively) and high to moderate inhibitory activity in two-electrode voltage clamp experiments. The indazole bioisosteres 10 and 11 showed higher metabolic stability than 1. In the presence of uridinyldiphosphate activated glucuronic acid, glucuronidation of 10 and 11 was not observed.

2024-11-06·ANTIMICROBIAL AGENTS AND CHEMOTHERAPY

The glutamate receptor antagonist ifenprodil inhibits hepatitis E virus infection

Article

作者: Todt, Daniel ; Gömer, André ; He, Qiyu ; Brown, Richard J. P. ; Steinmann, Eike ; Wang, Lin ; Klöhn, Mara

ABSTRACT:

Infection with hepatitis E virus (HEV) represents a global problem, with over 20 million people infected annually. No specific antiviral drugs are available for treating HEV infection, necessitating the development of novel targeted therapeutics. Here, we report that the N-methyl-D-aspartate receptor (NMDAR) antagonist ifenprodil, a clinically approved drug used to treat idiopathic pulmonary fibrosis (IPF), is an HEV inhibitor in liver-derived cells. In vitro investigation demonstrates that ifenprodil suppresses viral protein expression in a dose-dependent manner in human hepatoma cells by inhibiting early stages of viral infection. We also found that ifenprodil modulates host cell intrinsic biological processes distinct from virus-induced innate immunity, inhibiting HEV RNA accumulation in primary human hepatocytes. Finally, the inhibitory effect of ifenprodil in vivo was also tested in rabbits challenged with the HEV-3ra CHN-BJ-R14 strain. Fecal virus shedding was below the limit of detection in two animals for both ribavirin-treated and ifenprodil-treated rabbits compared to vehicle-treated control animals. Our data demonstrate that ifenprodil is an effective anti-HEV compound with potential as a therapeutic candidate for the treatment of HEV infection.

项与酒石酸艾芬地尔相关的新闻（医药）

2024-11-04

·algernonpharmaceuticals.com

Algernon Announces Warrant Extension

THIS NEWS RELEASE IS NOT FOR DISTRIBUTION TO U.S. NEWSWIRE SERVICES FOR DISSEMINATION IN THE UNITED STATES VANCOUVER, British Columbia, Nov. 04, 2024 (GLOBE NEWSWIRE) -- Algernon Pharmaceuticals Inc. (CSE: AGN) (FRANKFURT: AGW0) (OTCQB: AGNPF) (the “Company” or “Algernon”) a Canadian clinical stage pharmaceutical development company announces that it has extended the expiry date of an aggregate of 4,752,969 outstanding warrants (the “2023 Warrants”). The 2023 Warrants were issued in connection with the closing of a rights offering by the Company on May 5, 2023. The initial exercise price of the 2023 Warrants is $0.52 and remains unchanged. The 2023 Warrants have an original expiration date of November 5, 2024. The Company proposes to extend the expiration date of the 2023 Warrants by an additional six months, so that the 2023 Warrants will expire on May 5, 2025 (the “Amendment”). All other terms and conditions of the 2023 Warrants will remain unchanged. The Amendment is subject to final Canadian Securities Exchange (the “CSE”) approval; however, the CSE has granted an exemption from the requirements of Section 6.7(3)(c) (no warrants exercised in the last six months) and 6.7(3)(d) (at least 10 trading days remain before expiry) of CSE Policy 6 to permit the Company to undertake the Amendment. No action will be required on the part of the holders of the 2023 Warrants to give effect to the Amendment. In accordance with the requirements of the CSE, the terms of any warrants issued as compensation warrants or as finder warrants are not eligible for amendment. 400 of the 2023 Warrants have been exercised. 2,018,982 of the 2023 Warrants are owned by insiders of the Company, representing 42.5% of the aggregate number of 2023 Warrants. As a portion of the 2023 Warrants are held by insiders of the Company, the Amendment may constitute a “related party transaction” as defined under Multilateral Instrument 61-101 Protection of Minority Security Holders in Special Transactions (“MI 61-101”). A material change report will be filed with respect to the Amendment as it pertains to insiders. The Amendment are exempt from the formal valuation and minority shareholder approval requirements under MI 61-101 as neither the fair market value of the 2023 Warrants issued to insiders nor the cash consideration paid for such 2023 Warrants exceeds 25% of the market capitalization of the Company. The 2023 Warrants and the underlying Class A common shares have not been and will not be registered under the United States Securities Act of 1933, as amended (the "U.S. Securities Act"), or any state securities laws and may not be offered or sold within the United States or to, or for the account or benefit of, a U.S. person (as defined in Regulation S under the U.S. Securities Act) unless registered under the U.S. Securities Act and applicable state securities laws, or an exemption from such registration is available. This press release does not constitute an offer to sell or a solicitation of an offer to buy any of the securities referred to herein. About Algernon Pharmaceuticals Inc. Algernon Pharmaceuticals is a Canadian clinical stage drug development company investigating multiple drugs for unmet global medical needs. Algernon Pharmaceuticals is also the parent company of a private subsidiary called Algernon NeuroScience, that is advancing a psychedelic program investigating a proprietary form of DMT for stroke and traumatic brain injury. Algernon announced in March 2024, that it closed on its agreement with Seyltx Inc., a privately owned U.S. based drug development company, for the acquisition of Algernon’s Ifenprodil research program for the purchase price of USD $2M cash and a 20% common share equity position in Seyltx. For more information visit https://www.algernonpharmaceuticals.com. CONTACT INFORMATION Christopher J. Moreau CEO Algernon Pharmaceuticals Inc. 604.398.4175 ext 701 info@algernonpharmaceuticals.com investors@algernonpharmaceuticals.com www.algernonpharmaceuticals.com Neither the Canadian Securities Exchange nor its Market Regulator (as that term is defined in the policies of the Canadian Securities Exchange) accepts responsibility for the adequacy or accuracy of this release. CAUTIONARY DISCLAIMER STATEMENT: No Securities Exchange has reviewed nor accepts responsibility for the adequacy or accuracy of the content of this news release. This news release contains forward-looking statements relating to the Company, its future prospects and other statements that are not historical facts. Forward-looking statements are often identified by terms such as “will”, “may”, “should”, “anticipate”, “expects” and similar expressions. All statements other than statements of historical fact, included in this release are forward-looking statements that involve risks and uncertainties. There can be no assurance that such statements will prove to be accurate and actual results and future events could differ materially from those anticipated in such statements. Important factors that could cause actual results to differ materially from the Company’s expectations include the failure to satisfy the conditions of the relevant securities exchange(s) and other risks detailed from time to time in the filings made by the Company with securities regulations. The reader is cautioned that assumptions used in the preparation of any forward-looking information may prove to be incorrect. Events or circumstances may cause actual results to differ materially from those predicted, as a result of numerous known and unknown risks, uncertainties, and other factors, many of which are beyond the control of the Company. The reader is cautioned not to place undue reliance on any forward-looking information. Such information, although considered reasonable by management at the time of preparation, may prove to be incorrect and actual results may differ materially from those anticipated. Forward-looking statements contained in this news release are expressly qualified by this cautionary statement. The forward-looking statements contained in this news release are made as of the date of this news release and the Company will update or revise publicly any of the included forward-looking statements as expressly required by applicable law. Released November 4, 2024

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2024-08-20

·GlobeNewswire-Health Care

Algernon Pharmaceuticals Announces Closing of Private Placement

NOT FOR DISTRIBUTION TO U.S. NEWSWIRE SERVICES OR FOR DISSEMINATION IN THE UNITED STATES VANCOUVER, British Columbia, Aug. 20, 2024 (GLOBE NEWSWIRE) -- Algernon Pharmaceuticals Inc. (CSE: AGN) (FRANKFURT: AGW0) (OTCQB: AGNPF) (the “Company” or “Algernon”) a Canadian clinical stage pharmaceutical development company announces the close of its non-brokered private placement, previously announced on August 7, 2024 and updated on August 13, 2024, for gross proceeds of $235,200 (the “Offering”) of units (the “Units”) at an issue price of $0.12 per Unit. Certain insiders of the Company participated in the Offering in the amount of $60,000. The participation by insiders in the Offering constitutes a "related party transaction" as defined under Multilateral Instrument 61-101 Protection of Minority Security Holders in Special Transactions ("MI 61-101"). The Company is relying on the exemptions from the valuation and minority shareholder approval requirements of MI 61-101 contained in sections 5.5(a) and 5.7(1)(a) of MI 61-101, as neither the fair market value of the Common Shares purchased by insiders, nor the consideration for the Units paid by such insiders, exceeded 25% of the Company's market capitalization. The Company did not file a material change report in respect of the related party transaction at least 21 days before the closing of the Offering, which the Company deems reasonable in the circumstances as the details of the participation by insiders of the Company were not settled until shortly prior to closing the Offering and the Company wished to complete the Offering in an expeditious manner. The Company paid cash finder’s fees totaling $4,800 and issued 40,000 finders warrants to eligible finders for investors introduced to the Company by the eligible finder. The Company will use the proceeds of the private placement for working capital purposes. The securities issued and issuable, described in this news release, will be subject to a statutory hold period of four months plus a day from the date of issuance in accordance with applicable Canadian securities legislation. The securities have not been and will not be registered under the United States Securities Act of 1933, as amended (the “U.S. Securities Act”), or any state securities laws, and may not be offered or sold within the United States or to, or for the account or benefit of, “U.S. persons” (as such term is defined in Regulation S under the U.S. Securities Act) absent registration under the U.S. Securities Act and applicable state securities laws, or an exemption from such registration. About Algernon Pharmaceuticals Inc. Algernon Pharmaceuticals is a Canadian clinical stage drug development company investigating multiple drugs for unmet global medical needs. Algernon Pharmaceuticals is the parent company of a private subsidiary called Algernon NeuroScience, that is advancing a psychedelic program investigating a proprietary form of DMT for stroke and traumatic brain injury and has an active research program for chronic kidney disease. Algernon recently announced that it closed on its agreement with Seyltx Inc., a privately owned U.S. based drug development company, for the acquisition of Algernon’s Ifenprodil research program for the purchase price of USD $2M cash and a 20% common share equity position in Seyltx. For more information visit https://www.algernonpharmaceuticals.com. CONTACT INFORMATION Christopher J. Moreau CEO Algernon Pharmaceuticals Inc. 604.398.4175 ext 701 info@algernonpharmaceuticals.com investors@algernonpharmaceuticals.com www.algernonpharmaceuticals.com Neither the Canadian Securities Exchange nor its Market Regulator (as that term is defined in the policies of the Canadian Securities Exchange) accepts responsibility for the adequacy or accuracy of this release. CAUTIONARY DISCLAIMER STATEMENT: No Securities Exchange has reviewed nor accepts responsibility for the adequacy or accuracy of the content of this news release. This news release contains forward-looking statements relating to the completion of the Offering, use of proceeds from the Offering, engagement of Maxim, the completion of future transactions and the spin-off of the Ifenprodil research program and other statements that are not historical facts. Forward-looking statements are often identified by terms such as “will”, “may”, “should”, “anticipate”, “expects” and similar expressions. All statements other than statements of historical fact, included in this release are forward-looking statements that involve risks and uncertainties. There can be no assurance that such statements will prove to be accurate and actual results and future events could differ materially from those anticipated in such statements. Important factors that could cause actual results to differ materially from the Company’s expectations include the failure to satisfy the conditions of the relevant securities exchange(s) and other risks detailed from time to time in the filings made by the Company with securities regulations. The reader is cautioned that assumptions used in the preparation of any forward-looking information may prove to be incorrect. Events or circumstances may cause actual results to differ materially from those predicted, as a result of numerous known and unknown risks, uncertainties, and other factors, many of which are beyond the control of the Company. The reader is cautioned not to place undue reliance on any forward-looking information. Such information, although considered reasonable by management at the time of preparation, may prove to be incorrect and actual results may differ materially from those anticipated. Forward-looking statements contained in this news release are expressly qualified by this cautionary statement. The forward-looking statements contained in this news release are made as of the date of this news release and the Company will update or revise publicly any of the included forward-looking statements as expressly required by applicable law.

2024-08-13

·GlobeNewswire-Health Care

Algernon Pharmaceuticals Announces Increase to Private Placement

NOT FOR DISTRIBUTION TO U.S. NEWSWIRE SERVICES OR FOR DISSEMINATION IN THE UNITED STATES VANCOUVER, British Columbia, Aug. 13, 2024 (GLOBE NEWSWIRE) -- Algernon Pharmaceuticals Inc. (CSE: AGN) (FRANKFURT: AGW0) (OTCQB: AGNPF) (the “Company” or “Algernon”) a Canadian clinical stage pharmaceutical development company announces an increase to its non-brokered private placement, previously announced on August 7, 2024, from gross proceeds of $150,000 to $235,200 (the “Offering”) of units (the “Units”) at an issue price of $0.12 per Unit. Each Unit will consist of one Class A common share in the capital of the Company (a “Common Share”) and one Common Share purchase warrant (a “Warrant”). Each Warrant will entitle the holder to acquire one Common Share (a “Warrant Share”) at an exercise price of $0.24 per Warrant Share for a period of 2 years from the date of issuance (the “Expiry Date”), subject to acceleration of the Expiry Date as described below. The Offering is expected to close on August 16, 2024. The Warrants are subject to accelerated expiry in the event the volume weighted average trading price of the Common Shares exceeds $0.36 for 20 consecutive trading days, the Company may, within 10 business days of the occurrence of such event, deliver a notice to the holders of the Warrants accelerating the Expiry Date of the Warrants to a date that is not less than 30 days following the date of such notice and the issuance of a press release by the Company announcing the acceleration notice (the “Accelerated Exercise Period”). Any unexercised Warrants shall automatically expire at the end of the Accelerated Exercise Period. The Company may pay cash finder’s fees and finders warrants to eligible finders, up to eight percent of the proceeds raised and units issued for investors introduced to the Company by the eligible finder. The Company will use the proceeds of the private placement for working capital purposes. The securities issued and issuable, described in this news release, will be subject to a statutory hold period of four months plus a day from the date of issuance in accordance with applicable Canadian securities legislation. The securities have not been and will not be registered under the United States Securities Act of 1933, as amended (the “U.S. Securities Act”), or any state securities laws, and may not be offered or sold within the United States or to, or for the account or benefit of, “U.S. persons” (as such term is defined in Regulation S under the U.S. Securities Act) absent registration under the U.S. Securities Act and applicable state securities laws, or an exemption from such registration. About Algernon Pharmaceuticals Inc. Algernon Pharmaceuticals is a Canadian clinical stage drug development company investigating multiple drugs for unmet global medical needs. Algernon Pharmaceuticals is the parent company of a private subsidiary called Algernon NeuroScience, that is advancing a psychedelic program investigating a proprietary form of DMT for stroke and traumatic brain injury and has an active research program for chronic kidney disease. Algernon recently announced that it closed on its agreement with Seyltx Inc., a privately owned U.S. based drug development company, for the acquisition of Algernon’s Ifenprodil research program for the purchase price of USD $2M cash and a 20% common share equity position in Seyltx. For more information visit https://www.algernonpharmaceuticals.com. CONTACT INFORMATION Christopher J. Moreau CEO Algernon Pharmaceuticals Inc. 604.398.4175 ext 701 info@algernonpharmaceuticals.com investors@algernonpharmaceuticals.com www.algernonpharmaceuticals.com Neither the Canadian Securities Exchange nor its Market Regulator (as that term is defined in the policies of the Canadian Securities Exchange) accepts responsibility for the adequacy or accuracy of this release. CAUTIONARY DISCLAIMER STATEMENT: No Securities Exchange has reviewed nor accepts responsibility for the adequacy or accuracy of the content of this news release. This news release contains forward-looking statements relating to the completion of the Offering, use of proceeds from the Offering, engagement of Maxim, the completion of future transactions and the spin-off of the Ifenprodil research program and other statements that are not historical facts. Forward-looking statements are often identified by terms such as “will”, “may”, “should”, “anticipate”, “expects” and similar expressions. All statements other than statements of historical fact, included in this release are forward-looking statements that involve risks and uncertainties. There can be no assurance that such statements will prove to be accurate and actual results and future events could differ materially from those anticipated in such statements. Important factors that could cause actual results to differ materially from the Company’s expectations include the failure to satisfy the conditions of the relevant securities exchange(s) and other risks detailed from time to time in the filings made by the Company with securities regulations. The reader is cautioned that assumptions used in the preparation of any forward-looking information may prove to be incorrect. Events or circumstances may cause actual results to differ materially from those predicted, as a result of numerous known and unknown risks, uncertainties, and other factors, many of which are beyond the control of the Company. The reader is cautioned not to place undue reliance on any forward-looking information. Such information, although considered reasonable by management at the time of preparation, may prove to be incorrect and actual results may differ materially from those anticipated. Forward-looking statements contained in this news release are expressly qualified by this cautionary statement. The forward-looking statements contained in this news release are made as of the date of this news release and the Company will update or revise publicly any of the included forward-looking statements as expressly required by applicable law.

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100 项与酒石酸艾芬地尔相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D01445	酒石酸艾芬地尔	C04AX28	DB08954

研发状态

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适应症	国家/地区	公司	日期
眩晕	日本	Sanofi KK	1982-03-30

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适应症	最高研发状态	国家/地区	公司	日期
新型冠状病毒感染	临床3期	美国	Algernon Pharmaceuticals, Inc.	2020-08-05
新型冠状病毒感染	临床3期	澳大利亚	Algernon Pharmaceuticals, Inc.	2020-08-05
新型冠状病毒感染	临床3期	菲律宾	Algernon Pharmaceuticals, Inc.	2020-08-05
新型冠状病毒感染	临床3期	罗马尼亚	Algernon Pharmaceuticals, Inc.	2020-08-05
咳嗽	临床2期	澳大利亚	Algernon Pharmaceuticals, Inc.	2020-07-29
咳嗽	临床2期	新西兰	Algernon Pharmaceuticals, Inc.	2020-07-29
特发性肺纤维化	临床2期	澳大利亚	Algernon Pharmaceuticals, Inc.	2020-07-29
特发性肺纤维化	临床2期	新西兰	Algernon Pharmaceuticals, Inc.	2020-07-29

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


GlobeNewswire 人工标引	临床2期	特发性肺纤维化 \| 慢性咳嗽	-	Ifenprodil	積觸積製鑰遞壓鹹夢築(艱觸鑰蓋膚餘簾積襯蓋) = 衊鹹窪淵築餘廠積醖築淵鬱製夢鹽齋夢觸壓憲 (鹹夢鑰壓壓醖鑰醖鏇餘 ) 更多	积极	2023-11-22
NCT04318704 (GlobeNewswire) 人工标引	临床2期	特发性肺纤维化 \| 慢性咳嗽	-	NP-120	築夢獵淵鏇選壓構窪鑰(糧網獵築鹹鹽積糧構獵) = no worsening 鬱顧窪襯鏇鹹遞鹽鏇淵 (窪鏇繭製製鑰鏇鹽顧選 ) 更多	积极	2022-09-01