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更新于：2025-04-22
Arbutus Biopharma Corp.
更新于：2025-04-22
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NCT06154278
Pilot Study to Evaluate Intrahepatic and Peripheral Responses to Small Interfering RNA, Imdusiran (AB-729), Among People With Chronic Hepatitis B
NCT06277037
A Long-Term Follow-up Study for Subjects With Chronic Hepatitis B Previously Treated With Imdusiran (AB-729)
NCT06245291
A Phase 2a, Open-Label Multiple Dose Study Evaluating the Safety, Tolerability, and Pharmacodynamics of Imdusiran (AB-729) in Combination With Intermittent Dosing of Durvalumab, a PD-L1 Monoclonal Antibody, in Subjects With Chronic HBV Infection
100 项与 Arbutus Biopharma Corp. 相关的临床结果
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2025-03-21ORGANIC PROCESS RESEARCH & DEVELOPMENT
Development of a Scalable Manufacturing Process for AB-343 Drug Substance: A Potential Candidate for the Treatment of Coronavirus Infections
作者: Liu, Jia ; Vega, Marvin Marcus ; Mason, Jeremy D. ; Spink, Jan M. ; Wang, Xu ; Wu, Zhenhua ; Pallerla, Mahesh ; Pamulapati, Ganapati Reddy ; Singh, Rajeev K. ; Sofia, Michael J. ; Pulipaka, Aravind B.
A scalable process for manufacturing of the anticoronavirus clin. candidate AB-343 has been developed.The lactam-containing subunit of the mol. was prepared using a novel synthetic route involving a nitro-Michael reaction and a rhodium-catalyzed nitro group hydrogenation followed by in situ translactamization sequence as a key transformation.The drug substance was assembled via sequential amide coupling and deprotection reactions, followed by a final dehydration of a primary amide to the corresponding nitrile using T3P.AB-343 drug substance was successfully manufactured on a multikilogram scale using this route, which was suitable for supporting IND-enabling studies and Phase I clin. development.
2024-12-01ANTIVIRAL RESEARCH
Biological characterization of AB-343, a novel and potent SARS-CoV-2 Mpro inhibitor with pan-coronavirus activity
Article
作者: Cole, Andrew G ; Blaesse, Michael ; Sofia, Michael J ; Tercero, Breanna ; Weiss, Susan R. ; Vega, Marvin ; Weiss, Susan R ; Cole, Andrew G. ; Kultgen, Steven G ; von König, Konstanze ; Gotchev, Dimitar ; Bracci, Nicole ; Konz Makino, Debora L ; Chen, Chia-Yi ; Kultgen, Steven G. ; McGovern-Gooch, Kayleigh R ; Bergmann, Andreas ; Maskos, Klaus ; McGovern-Gooch, Kayleigh R. ; Kowalski, Rose ; Prasad, Archna ; Micolochick Steuer, Holly M ; Konz Makino, Debora L. ; Wasserman, Adam ; Chen, Chia-yi ; Fan, Kristi Y. ; Wang, Xiaohe ; Cuconati, Andrea ; Fan, Kristi Y ; Micolochick Steuer, Holly M. ; Sofia, Michael J. ; Sheraz, Muhammad ; Lindstrom, Aaron ; Mani, Nagraj ; Lam, Angela M. ; Wang, Xu ; Lam, Angela M ; Nguyen, Duyan ; Ardzinski, Andrzej
Since the SARS-CoV-2 outbreak, there have been ongoing efforts to identify antiviral molecules with broad coronavirus activity to combat COVID-19. SARS-CoV-2's main protease (Mpro) is responsible for processing the viral polypeptide into non-structural proteins essential for replication. Here, we present the biological characterization of AB-343, a covalent small-molecule inhibitor of SARS-CoV-2 Mpro with potent activity in both cell-based (EC50 = 0.018 μM) and enzymatic (Ki = 0.0028 μM) assays. AB-343 also demonstrated excellent inhibition of Mpro of other human coronaviruses, including those from the alpha (229E and NL63) and beta (SARS-CoV, MERS, OC43, and HKU1) families, suggesting the compound could be active against future coronaviruses. No change in AB-343 potency was observed against Mpro of SARS-CoV-2 variants of concern, including Omicron, suggesting that AB-343 could be developed as a treatment against currently circulating coronaviruses. AB-343 also remained active against several Mpro variants which confer significant resistance to nirmatrelvir and ensitrelvir, which are presently the only Mpro inhibitors authorized for the treatment of COVID-19, further supporting the evaluation of AB-343 as a novel and potent therapeutic for COVID-19 and other coronaviruses.
2024-11-14JOURNAL OF MEDICINAL CHEMISTRY
Rational Design of Macrocyclic Noncovalent Inhibitors of SARS-CoV-2 Mpro from a DNA-Encoded Chemical Library Screening Hit That Demonstrate Potent Inhibition against Pan-Coronavirus Homologues and Nirmatrelvir-Resistant Variants
Article
作者: Konz Makino, Debora L. ; Tercero, Breanna ; Johnstone, Shawn ; Cole, Andrew G. ; Cuconati, Andrea ; Gotchev, Dimitar ; Preuss, Franziska ; Chen, Chia-yi ; Clark, Matthew A. ; Maskos, Klaus ; Guilinger, John P. ; Centrella, Paolo A. ; Schmitt, Andreas ; Keefe, Anthony D. ; Prasad, Archna ; Vega, Marvin M. ; Wang, Xiaohe ; Turcotte, Stéphane ; Sofia, Michael J. ; Fan, Kristi Yi ; Carpino, Philip ; von König, Konstanze ; Mani, Nagraj ; McGovern-Gooch, Kayleigh ; Zhang, Ying ; Wang, Xu ; Liu, Jenny ; Lam, Angela M.
The recent global COVID-19 pandemic has highlighted treatments for coronavirus infection as an unmet medical need. The main protease (Mpro) has been an important target for the development of SARS-CoV-2 direct-acting antivirals. Nirmatrelvir as a covalent Mpro inhibitor was the first such approved therapy. Although Mpro inhibitors of various chemical classes have been reported, they are generally less active against nirmatrelvir-resistant variants and have limited pan-coronavirus potential, presenting a significant human health risk upon future outbreaks. We here present a novel approach and utilized DNA-encoded chemical library screening to identify the noncovalent Mpro inhibitor 5, which demonstrated a distinct binding mode to nirmatrelvir. A macrocyclization strategy designed to lock the active conformation resulted in lactone 12 with significantly improved antiviral activity. Further optimization led to the potent lactam 26, which demonstrated exceptional potency against nirmatrelvir-resistant variants as well as against a panel of viral main proteases from other coronaviruses.
2025-04-09
信使RNA疫苗财报
2025-03-20
2025-03-10
·药渡
信使RNA疫苗核酸药物临床申请
100 项与 Arbutus Biopharma Corp. 相关的药物交易
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