A Phase 2a, Randomized, Open-Label Study to Determine the Optimal Dose and Evaluate the Safety, Tolerability, and Pharmacokinetics of Progerinin in Patients With Hutchinson-Gilford Progeria Syndrome (HGPS)

Researchers will compare treatment with progerinin plus lonafarnib vs lonafarnib alone to assess optimal dosing, safety, tolerability, and pharmacokinetics in patients with Hutchinson-Gilford Progeria Syndrome (HGPS). Subjects in the randomized study arms will continue to take the standard of care (SOC), lonafarnib, and will be randomized to either take SOC alone or in combination with progerinin.

开始日期2025-01-13

申办/合作机构

PRG S&T Co., Ltd

NCT05953545

/ Withdrawn临床2期IIT

Open Label Phase 2 Clinical Study of Peginterferon Lambda and Lonafarnib Boosted With Ritonavir 48-Week Combination Therapy for Delta Hepatitis

Background:
Chronic hepatitis D is a serious liver disease caused by a virus. Currently, no medications are approved to treat chronic hepatitis D.
Objective:
To test a combination of 3 drugs in people with chronic hepatitis D.
Eligibility:
People 18 years or older with chronic hepatitis D.
Design:
Participants will be in the study about 2 years. They will have 3 inpatient stays of 3 to 5 days.
Participants will be screened. They will have a physical exam with blood tests. They will have a test of their heart function and an ultrasound: a wand that uses sound waves to create images of the liver will be rubbed over the skin on their torso.
Participants will stay in the clinic for a 3-day baseline visit. They will have imaging scans, an eye exam, and a visit with a reproductive specialist. They will have a liver biopsy: about 1 inch of liver tissue will be removed, either with a tube inserted through a vein in the neck, or with a needle inserted through the participant s side.
Participants will take the study drugs for 48 weeks. Two of them are tablets taken twice a day at home; 1 is a shot administered once a week. Participants will begin taking the drugs during a 5-day stay in the clinic. Then they will have 15 outpatient visits while taking the drugs and 7 more after they finish.
The last 3-day clinic stay will be 6 months after participants finish taking the drugs. The liver biopsy, imaging scans, and other tests will be repeated.

开始日期2024-05-22

申办/合作机构

National Institute of Diabetes & Digestive & Kidney Diseases

ChiCTR2100050052

/ Not yet recruitingN/AIIT

Observational study of Lonafarnib in Chinese patients with progeria and progeroid laminopathy

开始日期2021-08-18

申办/合作机构

浙江大学医学院附属儿童医院

100 项与洛那法尼相关的临床结果

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100 项与洛那法尼相关的转化医学

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100 项与洛那法尼相关的专利（医药）

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273

项与洛那法尼相关的文献（医药）

2026-03-01·EUROPEAN JOURNAL OF PHARMACOLOGY

Heat stroke-induced structural and functional impairments of cognition-relevant brain areas in mice is associated with alpha-7 nicotinic acetylcholine receptors downregulation

Article

作者: Shi, Yunfei ; Liu, Ruoxu ; Yan, Liyong ; Wang, Xiaowen ; Ma, Tao ; Yi, Xueqing ; Lin, Xiaojing ; Liu, Kai ; Zhang, Kangli ; Sun, Gang ; Liu, Xiaohong ; Qu, Zixuan ; Ye, Zhujun ; Wang, Lin-Yu ; Lin, Cheng-Hsien ; Li, Chenyi

OBJECTIVE:

Classic heat stroke (CHS) results from prolonged exposure to high environmental temperatures without physical exertion. However, the involvement of α7 nicotinic acetylcholine receptors (α7nAChR) in CHS-associated neurobehavioral abnormalities remains unclear.

METHODS:

Immediately after CHS onset, mice received intraperitoneal lonafarnib (LNF-40; 40 mg/kg) or vehicle twice daily for 14 days. Animals were assigned to four groups: non-CHS+Veh, non-CHS+LNF-40, CHS+Veh, and CHS+LNF-40. After the final dose, neurobehavioral performance was evaluated using novel object recognition, forced swim, rotarod, and Morris water maze tests. Dendritic morphology of prefrontal cortical neurons was assessed by Golgi staining, whereas hippocampal neurogenesis was evaluated by doublecortin (DCX) immunofluorescence. Finally, α7nAChR levels and pro-inflammatory cytokines in the prefrontal cortex and hippocampus were quantified by ELISA.

RESULTS:

Compared with non-CHS controls, CHS+Veh mice exhibited impaired recognition and spatial memory, increased depressive-like behavior, and reduced motor coordination. Relative to CHS+Veh, CHS+LNF-40 mice showed attenuated neurobehavioral deficits. Structurally, Golgi analyses indicated that LNF-40 reduced CHS-associated dendritic/spine pathology in prefrontal cortical neurons, and DCX immunofluorescence showed higher hippocampal neurogenesis in LNF-40-treated CHS mice. Biochemically, LNF-40 was associated with higher α7 nAChR levels and lower pro-inflammatory cytokines in both the prefrontal cortex and hippocampus. LNF-40 did not significantly alter these measures in non-CHS mice.

CONCLUSION:

CHS is associated with structural and functional impairments in cognition-relevant brain regions, accompanied by reduced α7nAChR expression. Lonafarnib mitigated CHS-related neurobehavioral abnormalities in parallel with restoration of α7nAChR expression in mice.

2026-02-01·ANTICANCER RESEARCH

Targeted Sensitization of Leukemic T-cells to Anticancer Drugs by SIRT1 Agonist SRT-1720.

Article

作者: Ivanova, Donika ; Bakalova, Rumiana ; Getsov, Plamen ; Lazarova, Dessislava ; Nikolova, Biliana ; Hadjidekov, Vasil ; Zhelev, Zhivko

BACKGROUND/AIM:

Leukemia therapy targets multiple molecular pathways, including non-oncogenic but clinically relevant factors such as Silent Information Regulator 1 (SIRT1), which acts either as a tumor suppressor or tumor promoter depending on its downstream targets, cancer type, and disease stage. Although small-molecule SIRT1 activators such as SRT-1720 have shown anticancer potential, their molecular mechanisms in leukemia remain insufficiently understood. This study aimed to elucidate the effects of SRT-1720 on the redox state and viability of leukemic lymphocytes and normal lymphocytes, as well as its ability to sensitize leukemic cells to anticancer drugs.

MATERIALS AND METHODS:

The synergistic, additive or antagonistic antiproliferative effects of SRT-1720 and anticancer drugs were examined. The following parameters were analyzed: cell viability and proliferation - by trypan blue staining; apoptosis - by phosphatidylserine expression on the cell surface; and oxidative stress - by detecting intracellular levels of reactive oxygen species (ROS) and protein carbonyl products.

RESULTS:

SRT-1720 potentiated the effects of most anticancer drugs in leukemic lymphocytes. Synergism was found in combination with: barasertib, bortezomib, cisplatin, MG-132, bleomycin, ABT-737, lonafarnib, everolimus, and palbociclib. SRT-1720 increased the tolerance of normal lymphocytes to anticancer drugs, as demonstrated for everolimus, barasertib, and doxorubicin. The synergistic cytotoxicity of SRT-1720 in combination with everolimus and barasertib was accompanied by overproduction of ROS and increased induction of apoptosis in leukemic lymphocytes, but not in normal lymphocytes. SRT-1720 favorably affected the viability of normal lymphocytes, reducing oxidative stress and cytotoxicity induced by doxorubicin at the concentrations used in our study.

CONCLUSION:

SRT-1720 induces oxidative stress and apoptosis in leukemic lymphocytes through SIRT1-independent pathway(s). In contrast, it enhances antioxidant defense in normal lymphocytes through a SIRT1-dependent pathway. These findings highlight the potential of SRT-1720 as an adjuvant to chemotherapy in T-ALL, particularly in drug combinations demonstrating strong synergism, which may allow dose reduction and decreased toxicity.

2026-01-20·JOURNAL OF VIROLOGY

Molecular mechanism of resistance to lonafarnib conferred by mutations in the cysteine-rich region of respiratory syncytial virus fusion glycoprotein and discovery of a lonafarnib-derived antiviral PROTAC

Article

作者: Tang, Wei ; Zou, Jingjing ; Xue, Bao ; Xu, Xi ; Zhang, Wei ; Zhang, Qiong ; Zhou, Yuan ; Yang, Kaixin ; Zhong, Jiayi ; Shang, Jinsai ; Xiao, Qingyu ; Ye, Wencai ; Mao, Yuhan ; Yang, Qi ; Zhou, Anqi ; Li, Yixue ; Chen, Xinwen ; Tang, Jielin ; Peng, Wei ; Li, Zhiyu ; Qiu, Xianjie ; Zou, Gang

ABSTRACT:

Lonafarnib, an oral antiviral that targets the fusion glycoprotein of respiratory syncytial virus (RSV), has demonstrated efficacy in vitro and in vivo . However, because the RSV has evolved to become resistant to other fusion inhibitors, there is a concern that the same could occur for lonafarnib. Here, we identified resistance to lonafarnib in the RSV A2 strain and a recent clinical isolate, RSV ON1, via in vitro selection at scale. Cell‒cell fusion and recombinant live RSV analysis confirmed that the mutations at K394, K399, and T400 of the cysteine-rich region of the fusion protein mediate high-level resistance. Lonafarnib resistance mutations also confer cross-resistance to other fusion inhibitors of clinical interest. All-atom molecular dynamics simulations revealed that these resistance mutations confer reduced stability to the fusion protein, thereby diminishing its binding affinity with lonafarnib. To address this vulnerability proactively and increase the barrier to resistance development, we designed the first potent proteolysis-targeting chimera (PROTAC) fusion protein degrader, compound 0179841, which uses lonafarnib and cereblon as ligands. This PROTAC effectively inhibited RSV replication. Collectively, our findings indicate that RSV develops resistance to lonafarnib in the cysteine-rich region of the fusion protein. This work sheds light on the mechanisms by which RSV evolves resistance to lonafarnib and provides a foundation for the rational design of antivirals aimed at preventing resistance.

IMPORTANCE:

Respiratory syncytial virus (RSV) infection poses a substantial public health challenge. Resistance to several potent fusion inhibitors, which are currently in various stages of clinical development, can readily emerge. Through a drug repurposing screen, we identified lonafarnib as an RSV fusion inhibitor; however, concerns exist regarding the potential development of resistance. Here, large-scale in vitro selection experiments revealed specific mutations within the highly conserved cysteine-rich region of the fusion (F) protein that confer high-level lonafarnib resistance across diverse RSV strains. These resistance mutations also confer cross-resistance to other clinical-stage fusion inhibitors. Mechanistic investigations demonstrated that these mutations reduce F protein stability, thereby diminishing the binding affinity of lonafarnib. As a proof of concept for an alternative antiviral strategy, we rationally designed the first potent proteolysis-targeting chimera (PROTAC) F protein degrader, compound 0179841, by utilizing lonafarnib and cereblon ligands. This novel antiviral agent effectively inhibits RSV infection by inducing degradation of the F protein. This work elucidates the molecular basis of RSV resistance to lonafarnib and establishes a strategy for developing next-generation antivirals aimed at preempting resistance.

项与洛那法尼相关的新闻（医药）

2026-03-17

·PRNewswire

Sentynl Therapeutics Enters into Agreement with PRG S&T to License Molecule for Hutchinson-Gilford Progeria Syndrome

Sentynl will acquire full rights to the investigational drug candidate, Progerinin (SLC-D011), adding to its commercial portfolio of rare and ultra-rare disease products March 16, 2026-- Sentynl Therapeutics Inc. (" Sentynl"), a U.S.-based biopharmaceutical company and wholly-owned subsidiary of Zydus Lifesciences Limited (" Zydus"), announced that it is entering into an agreement with PRG S&T, a Korean company specializing in the development of medicine for rare genetic diseases, to license its investigational molecule Progerinin (SLC-D011) for Hutchinson-Gilford Progeria Syndrome (HGPS or "progeria"). The agreement will allow Sentynl to begin working with PRG S&T immediately to advance the clinical development of Progerinin (SLC-D011) for HGPS, which has been designated as an orphan drug by the United States Food and Drug Administration (FDA). Under the conditions that certain milestones are met, Sentynl will acquire full rights to the molecule for HGPS upon closing, making Progerinin the company's second therapy intended for the treatment of HGPS. The program is currently finalizing a Phase 2A clinical trial and data are expected before the end of 1H 2026. "This acquisition marks an important step in growing our portfolio of therapies for Hutchinson-Gilford Progeria Syndrome, which can have severe impacts on patient health if left untreated," said Dr. Sharvil P. Patel, Managing Director, Zydus Lifesciences Limited. "Supporting patients in living healthy, fulfilled lives is core to what we do, and the agreement with PRG S&T directly furthers this mission by advancing orphan therapies for patients and families impacted by rare diseases." "Children with Hutchinson-Gilford Progeria Syndrome face an unforgiving disease. However, we are seeing real progress in progeria research, with new science changing what's possible," said Matt Heck, CEO, Sentynl. "This agreement, which will add Progerinin to our progeria portfolio, represents our commitment to translating that progress into another real therapy for children and families who need them." Progerinin is an investigational, orally active small-molecule drug being developed as a potential treatment for Hutchinson-Gilford Progeria Syndrome, a rare genetic disorder characterized by accelerated aging in children. The disease is caused by the accumulation of progerin, an abnormal form of the lamin A protein produced by mutations in the LMNA gene, which disrupts nuclear structure and leads to premature cellular aging. Progerinin is designed to inhibit the interaction and harmful effects of progerin within cells, thereby improving nuclear integrity and reducing cellular damage. It is not currently approved by FDA or any other health authority. "The Progeria Research Foundation (PRF) is proud to have funded the foundational research that led to the development of Progerinin, and we are happy to see this potential path moving forward," said Leslie Gordon, MD, PhD, Medical Director at Progeria Research Foundation. "PRF's mission is to find treatments and the cure for Progeria, and we are grateful for the efforts of PRG S&T and Sentynl to improve the lives of the children and young adults in our Progeria patient community." Early research and clinical trials aim to determine whether Progerinin can slow disease progression and improve survival in HGPS patients, potentially offering another therapeutic option. Currently, Zokinvy® (lonafarnib) is the only approved treatment for HGPS and certain processing-deficient Progeroid Laminopathies in the U.S., European Union, Great Britan, Israel, and Japan. Progerinin is a small-molecule drug candidate being developed to treat Hutchinson-Gilford Progeria Syndrome (HGPS), a rare genetic disorder that causes rapid aging in children. It works by targeting progerin, an abnormal protein produced from a mutation in the LMNA gene. In HGPS, this mutation causes cells to produce progerin instead of normal lamin A, which leads to defects in the cell nucleus and accelerates aging symptoms. In mouse models of HGPS, progerinin demonstrated encouraging outcomes. In mice with a severe form of the disease, treatment increased lifespan by 8–10 weeks and improved body weight. The untreated control group had a shorter lifespan (average = 16.8 weeks; maximum = 18 weeks), whereas the treated group exhibited a significantly extended lifespan (average = 25.2 weeks; maximum = 26 weeks; p LMNA point mutation that produces the farnesylated lamin A variant, progerin, via aberrant splicing. Progeroid laminopathies are genetic disorders of accelerated aging caused by mutations in LMNA and/or ZMPSTE24 that impair lamin A processing, resulting in the accumulation of farnesylated prelamin A proteins including progerin.2,3 Children with HGPS commonly die of atherosclerosis, the same heart disease that affects millions of normally aging adults by an average age of 14.5 years. Disease manifestations include severe failure to thrive, scleroderma-like skin, global lipodystrophy, alopecia, joint contractures, skeletal dysplasia, global accelerated atherosclerosis with cardiovascular decline, and debilitating strokes.1 Zydus Lifesciences Limited is an innovation-led life-sciences company with leadership positions across pharmaceuticals and consumer wellness, supported by an emerging MedTech franchise and a global footprint across the United States, India and other international markets. As of September 30, 2025, the group employs 29,000 people worldwide including 1,500 scientists engaged in R&D and is driven by its mission to unlock new possibilities in life sciences through quality healthcare solutions that impact lives. The group aspires to transform lives through path-breaking discoveries. Sentynl Therapeutics Inc. (" Sentynl") is a commercial stage U.S.-based biopharmaceutical company focused on bringing innovative therapies to patients living with rare diseases. Recognized for its commitment to the rare disease community, Sentynl leverages its global operations as well as its parent organization, Zydus Group, to advance the development, manufacturing, and delivery of treatments to patients who need them in numerous countries worldwide. Sentynl is dedicated to improving patient outcomes and access while upholding ethical standards and operating in compliance with applicable laws, regulations, and industry guidelines. For more information, visit https://sentynl.com. PRG S&T is a research & development company specializing in the treatment of rare genetic diseases. PRG S&T has been developing therapeutics for rare genetic diseases (laminopathies, neurodegenerative diseases, neuro-oncology etc.) with small molecules, which are derived from target sites on aberrant Protein-Protein Interactions (PPI). Resources 1. Gordon LB, Brown WT, Collins FS. Hutchinson-Gilford Progeria Syndrome. 2003 Dec 12 [Updated 2019 Jan 17]. In: Adam MP, Ardinger HH, Pagon RA, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2020. 2. Gordon LB, Shappell H, Massaro J, et al. Association of lonafarnib treatment vs no treatment with mortality rate in patients with Hutchinson-Gilford progeria syndrome. JAMA. 2018;319(16):1687-1695. doi:10.1001/jama.2018.3264. 3. Marcelot A, Worman HJ, and Zinn-Justin S. Protein structural and mechanistic basis of progeroid laminopathies. FEBS Journal. 2021:288:2757-2772. Doi:10.111/febs.15526. The content above comes from the network. if any infringement, please contact us to modify.

孤儿药引进/卖出上市批准并购

2026-03-16

·动脉网

Sentynl Therapeutics与PRG S&T达成协议，授权获得哈钦森-吉尔福德早衰综合征分子许可Sentynl Therapeutics Enters into Agreement with PRG S&T to License Molecule for Hutchinson-Gilford Progeria Syndrome

Sentynl will acquire full rights to the investigational drug candidate, Progerinin (SLC-D011), Sentynl将获得在研药物候选物Progerinin（SLC-D011）的全部权利，adding to its commercial portfolio of rare and ultra-rare disease products 进一步丰富其罕见和超罕见疾病产品的商业组合AHMEDABAD, India and SOLANA BEACH, Calif. 印度艾哈迈达巴德和美国加利福尼亚州索拉纳海滩, ，March 16, 2026 2026年3月16日/PRNewswire/ -- /PRNewswire/ --Sentynl Therapeutics Inc. 森蒂尼尔治疗公司(' ('Sentynl 森蒂尼尔'), a U.S.-based biopharmaceutical company and wholly-owned subsidiary of Zydus Lifesciences Limited (' “），一家总部位于美国的生物制药公司，也是 Zydus Lifesciences Limited 的全资子公司（“Zydus 齐迪斯'), announced that it is entering into an agreement with “），宣布将与某公司达成协议，PRG S&T PRG 科技与创新, a Korean company specializing in the development of medicine for rare genetic diseases, to license its investigational molecule Progerinin (SLC-D011) for Hutchinson-Gilford Progeria Syndrome (HGPS or 'progeria'). ，一家专注于罕见遗传病药物开发的韩国公司，将其研究分子Progerinin（SLC-D011）授权用于治疗哈钦森-吉尔福德早衰综合症（HGPS或“早衰症”）。The agreement will allow Sentynl to begin working with PRG S&T immediately to advance the clinical development of Progerinin (SLC-D011) for HGPS, which has been designated as an orphan drug by the United States Food and Drug Administration (FDA). Under the conditions that certain milestones are met, Sentynl will acquire full rights to the molecule for HGPS upon closing, making Progerinin the company's second therapy intended for the treatment of HGPS. 该协议将允许Sentynl立即与PRG S&T合作，推进Progerinin（SLC-D011）用于治疗HGPS的临床开发，该药物已被美国食品药品监督管理局（FDA）指定为孤儿药。在达到特定里程碑的条件下，Sentynl将在协议完成时获得该分子针对HGPS的全部权利，使Progerinin成为该公司第二种用于治疗HGPS的疗法。The program is currently finalizing a Phase 2A clinical trial and data are expected before the end of 1H 2026.. 该计划目前正在完成 2A 期临床试验，预计在 2026 年上半年结束前获得数据。'This acquisition marks an important step in growing our portfolio of therapies for Hutchinson-Gilford Progeria Syndrome, which can have severe impacts on patient health if left untreated,' said Dr. Sharvil P. Patel, Managing Director, Zydus Lifesciences Limited. 'Supporting patients in living healthy, fulfilled lives is core to what we do, and the agreement with PRG S&T directly furthers this mission by advancing orphan therapies for patients and families impacted by rare diseases.'. “此次收购标志着我们在扩展针对哈钦森-吉尔福德早衰综合征的疗法组合方面迈出了重要一步，如果不进行治疗，这种疾病可能对患者的健康造成严重影响，”Zydus Lifesciences Limited董事总经理Sharvil P. Patel博士表示。“支持患者过上健康、充实的生活是我们工作的核心，与PRG S&T的协议通过推进针对罕见病影响的患者和家庭的孤儿药疗法，直接推动了这一使命。”'Children withHutchinson-Gilford Progeria Syndrome face an unforgiving disease. However, we are seeing real progress in progeria research, with new science changing what's possible,' said Matt Heck, CEO, Sentynl. 'This agreement, which will add Progerinin to our progeria portfolio, represents our commitment to translating that progress into another real therapy for children and families who need them.'. “患有哈钦森-吉尔福德早衰症的儿童面临着一种无情的疾病。然而，我们在早衰症研究中看到了真正的进展，新的科学正在改变可能性，”Sentynl首席执行官马特·赫克表示。“这项协议将把Progerinin加入我们的早衰症产品组合，代表了我们将这一进展转化为另一种真正疗法的决心，为需要帮助的儿童和家庭提供支持。”Progerinin is an investigational, orally active small-molecule drug being developed as a potential treatment for Hutchinson-Gilford Progeria Syndrome, a rare genetic disorder characterized by accelerated aging in children. The disease is caused by the accumulation of progerin, an abnormal form of the lamin A protein produced by mutations in the . Progerinin是一种在研的、口服活性小分子药物，正在被开发作为治疗哈钦森-吉尔福德早衰综合征的潜在药物，这是一种罕见的遗传疾病，其特征是儿童出现加速衰老。该疾病由早老素（progerin）的积累引起，早老素是由基因突变产生的异常形式的核纤层蛋白A。LMNA LMNAgene, which disrupts nuclear structure and leads to premature cellular aging. Progerinin is designed to inhibit the interaction and harmful effects of progerin within cells, thereby improving nuclear integrity and reducing cellular damage. It is not currently approved by FDA or any other health authority.. 基因，它破坏核结构并导致细胞过早衰老。Progerinin旨在抑制progerin在细胞内的相互作用及其有害影响，从而改善核完整性并减少细胞损伤。目前，它尚未获得FDA或任何其他卫生机构的批准。'The Progeria Research Foundation (PRF)is proud to have funded the foundationalresearch that led tothe developmentof Progerinin, and we are happy to see this potentialpath moving forward,' said Leslie Gordon, MD, PhD, Medical Director at Progeria Research Foundation. 'PRF's mission is to find treatments and the cure for Progeria, and we are grateful for the efforts of PRG S&T and Sentynl to improvethe lives of the children and young adults in our Progeria patient community.'. “普罗杰里亚研究基金会（PRF）为资助了导致Progerinin开发的基础研究感到自豪，我们很高兴看到这一潜在路径正在向前推进，”普罗杰里亚研究基金会医学主任莱斯利·戈登医学博士、哲学博士表示。“PRF的使命是寻找普罗杰里亚的治疗方法和治愈手段，我们对PRG S&T和Sentynl为改善我们普罗杰里亚患者社区中的儿童和年轻人的生活所做出的努力深表感谢。”Early research and clinical trials aim to determine whether Progerinin can slow disease progression and improve survival in HGPS patients, potentially offering another therapeutic option. Currently, Zokinvy 早期研究和临床试验旨在确定Progerinin是否能够减缓HGPS患者的疾病进展并提高生存率，可能提供另一种治疗选择。目前，Zokinvy® ®(lonafarnib) is the only approved treatment for HGPS and certain processing-deficient Progeroid Laminopathies in the U.S., European Union, Great Britan, Israel, and Japan. (lonafarnib) 是美国、欧盟、英国、以色列和日本唯一批准用于治疗 HGPS 和某些加工缺陷型早衰症核纤层蛋白病的药物。About Progerinin 关于ProgerininProgerinin is a small-molecule drug candidate being developed to treat Hutchinson-Gilford Progeria Syndrome (HGPS), a rare genetic disorder that causes rapid aging in children. It works by targeting progerin, an abnormal protein produced from a mutation in the 普罗杰林是一种小分子药物候选物，正在开发用于治疗哈钦森-吉尔福德早衰综合征 (HGPS)，这是一种导致儿童快速衰老的罕见遗传疾病。它通过靶向早衰素（一种由基因突变产生的异常蛋白质）起作用。LMNA LMNAgene. In HGPS, this mutation causes cells to produce progerin instead of normal lamin A, which leads to defects in the cell nucleus and accelerates aging symptoms. In mouse models of HGPS, progerinin demonstrated encouraging outcomes. In mice with a severe form of the disease, treatment increased lifespan by 8–10 weeks and improved body weight. 基因。在HGPS中，这种突变导致细胞产生早衰素而不是正常的核纤层蛋白A，这会引起细胞核缺陷并加速衰老症状。在HGPS的小鼠模型中，早衰素显示出令人鼓舞的结果。在患有严重形式疾病的小鼠中，治疗使寿命延长了8到10周，并改善了体重。The untreated control group had a shorter lifespan (average = 16.8 weeks; maximum = 18 weeks), whereas the treated group exhibited a significantly extended lifespan (average = 25.2 weeks; maximum = 26 weeks; p < 0.001).. 未处理的对照组寿命较短（平均 = 16.8 周；最长 = 18 周），而处理组的寿命显著延长（平均 = 25.2 周；最长 = 26 周；p < 0.001）。About Progeria 关于早衰症 Collectively known as progeria, Hutchinson-Gilford Progeria Syndrome and progeroid laminopathies are ultra-rare, fatal, genetic premature aging diseases that accelerate mortality in young patients.HGPS is caused by an 统称为早衰症，哈钦森-吉尔福德早衰症综合征和早衰样核纤层蛋白病是超罕见、致命的遗传性早衰疾病，会加速年轻患者的死亡。HGPS 是由LMNA LMNApoint mutation that produces the farnesylated lamin A variant, progerin, via aberrant splicing. Progeroid laminopathies are genetic disorders of accelerated aging caused by mutations in 通过异常剪接产生法尼基化早衰蛋白A变异体（早衰素）的点突变。早衰样层蛋白病是由加速衰老的基因突变引起的遗传疾病。LMNA LMNAand/or 和/或ZMPSTE24 ZMPSTE24that impair lamin A processing, resulting in the accumulation of farnesylated prelamin A proteins including progerin. 这些因素会损害lamin A的加工过程，导致包括progerin在内的法尼基化prelamin A蛋白的积累。2,3 2,3Children with HGPS commonly die of atherosclerosis, the same heart disease that affects millions of normally aging adults by an average age of 14.5 years. Disease manifestations include severe failure to thrive, scleroderma-like skin, global lipodystrophy, alopecia, joint contractures, skeletal dysplasia, global accelerated atherosclerosis with cardiovascular decline, and debilitating strokes.. 患有HGPS的儿童通常在平均14.5岁时死于动脉粥样硬化，这种心脏病同样影响着数百万正常衰老的成年人。疾病表现包括严重的生长不良、类似硬皮病的皮肤、全身性脂肪营养不良、脱发、关节挛缩、骨骼发育不良、全身加速性动脉粥样硬化伴心血管衰退以及致残性中风。1 1About Zydus Lifesciences Limited 关于Zydus Lifesciences有限公司Zydus Lifesciences Limited is an innovation-led life-sciences company with leadership positions across pharmaceuticals and consumer wellness, supported by an emerging MedTech franchise and a global footprint across the United States, India and other international markets. As of September 30, 2025, the group employs 29,000 people worldwide including 1,500 scientists engaged in R&D and is driven by its mission to unlock new possibilities in life sciences through quality healthcare solutions that impact lives. Zydus Lifesciences Limited 是一家创新驱动的生命科学公司，在制药和消费者健康领域占据领先地位，拥有新兴的医疗技术业务，并在美国、印度及其他国际市场具备全球影响力。截至 2025 年 9 月 30 日，该集团在全球拥有 29,000 名员工，其中包括 1,500 名从事研发的科学家，其使命是通过影响生命的优质医疗保健解决方案，开拓生命科学的新可能。The group aspires to transform lives through path-breaking discoveries. For more details visit . 该集团希望通过开创性的发现来改变生活。欲了解更多信息，请访问。https://www.zyduslife.com https://www.zyduslife.com. 。About Sentynl Therapeutics Inc 关于Sentynl Therapeutics IncSentynl Therapeutics Inc. (' Sentynl Therapeutics Inc.（Sentynl 森蒂尼尔') is a commercial stage U.S.-based biopharmaceutical company focused on bringing innovative therapies to patients living with rare diseases. Recognized for its commitment to the rare disease community, Sentynl leverages its global operations as well as its parent organization, Zydus Group, to advance the development, manufacturing, and delivery of treatments to patients who need them in numerous countries worldwide. ')是一家处于商业化阶段的美国生物制药公司，专注于为罕见病患者带来创新疗法。Sentynl因其对罕见病社区的承诺而受到认可，公司利用其全球业务以及母公司Zydus集团的资源，推动治疗药物的研发、生产和交付，为全球众多国家的患者提供所需治疗。Sentynl is dedicated to improving patient outcomes and access while upholding ethical standards and operating in compliance with applicable laws, regulations, and industry guidelines. For more information, visit. Sentynl致力于在遵守道德标准并符合适用法律法规和行业指南的前提下，改善患者的治疗效果和获取途径。欲了解更多信息，请访问。https://sentynl.com https://sentynl.com. 。About PRG S&T 关于PRG S&TPRG S&T is a research & development company specializing in the treatment of rare genetic diseases. PRG S&T has been developing therapeutics for rare genetic diseases (laminopathies, neurodegenerative diseases, neuro-oncology etc.) with small molecules, which are derived from target sites on aberrant Protein-Protein Interactions (PPI). PRG S&T 是一家专注于治疗罕见遗传疾病的研发公司。PRG S&T 一直致力于利用小分子开发针对罕见遗传疾病（如层蛋白病、神经退行性疾病、神经肿瘤学等）的治疗方法，这些小分子源自异常蛋白质-蛋白质相互作用 (PPI) 的靶点。For more information, please visit . 有关更多信息，请访问。www.eng.prgst.com www.eng.prgst.com. 。Resources 资源1. Gordon LB, Brown WT, Collins FS. Hutchinson-Gilford Progeria Syndrome. 2003 Dec 12 1. 戈登 LB，布朗 WT，柯林斯 FS。哈钦森-吉尔福德早衰症综合征。2003年12月12日[Updated [已更新 2019 Jan 17]. In: Adam MP, Ardinger HH, Pagon RA, et al., editors. GeneReviews® [Internet]. 2019年1月17日]。收录于：Adam MP、Ardinger HH、Pagon RA等，编辑。GeneReviews® [互联网]。Seattle (WA): 西雅图（华盛顿州）：University of Washington, 华盛顿大学，Seattle; 1993-2020. 西雅图；1993-2020。2. Gordon LB, Shappell H, Massaro J, et al. Association of lonafarnib treatment vs no treatment 2. Gordon LB, Shappell H, Massaro J, 等。lonafarnib治疗与无治疗的关联with mortality rate in patients with Hutchinson-Gilford progeria syndrome. JAMA. 患有哈钦森-吉尔福德早衰症综合征患者的死亡率。《美国医学会杂志》。2018;319(16):1687-1695. doi:10.1001/jama.2018.3264. 2018;319(16):1687-1695. doi:10.1001/jama.2018.3264.3. Marcelot A, Worman HJ, and 3. 马塞洛特 A，沃曼 HJ，和Zinn-Justin S. Protein structural and mechanistic basis of progeroid Zinn-Justin S. 蛋白质结构与早衰症的机制基础laminopathies. 层粘连蛋白病。FEBS Journal. 2021:288:2757-2772. Doi:10.111/febs.15526. FEBS Journal. 2021:288:2757-2772. Doi:10.111/febs.15526.SOURCE Sentynl Therapeutics 来源：Sentynl Therapeutics21 21% %more press release views with 更多新闻稿浏览量与 Request a Demo 请求演示

2026-03-16

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Sentynl Therapeutics expands rare disease pipeline with PRG S&T’s Progerinin

Sentynl Therapeutics, a US-based subsidiary of Indian firm Zydus Lifesciences, has entered into a licensing agreement with South Korean rare disease company PRG S&T to acquire rights to progerinin (SLC-D011), an investigational oral small-molecule drug candidate for Hutchinson-Gilford progeria syndrome (HGPS), as per the firm’s announcement. Sentynl will work with PRG S&T to advance clinical development of the progeria drug candidate. The program is currently in the final stages of a Phase IIa clinical trial, with data expected before the end of the first half of 2026. Progerinin holds US FDA orphan drug designation. Financial terms of the deal were not disclosed. The agreement is structured so that Sentynl will acquire full rights to Progerinin for HGPS upon closing, contingent on certain unspecified milestones being met. Progerinin is an orally active small molecule designed to inhibit the pathological interaction between progerin and normal cellular structures. HGPS is caused by a point mutation in the LMNA gene that produces progerin, an abnormal form of the lamin A protein. Progerin accumulates in cell nuclei, disrupting nuclear architecture and accelerating cellular aging. Children with the condition typically develop atherosclerosis, skeletal abnormalities, and cardiovascular decline, with an average lifespan of 14.5 years. Progerinin targets the binding interface between progerin and lamin A, aiming to restore nuclear integrity and reduce downstream cellular damage. In preclinical mouse models, treatment extended average lifespan from 16.8 weeks to 25.2 weeks and improved body weight. A Phase I study in healthy volunteers has been completed (NCT04512963). The deal positions Progerinin as Sentynl’s second therapy directed at HGPS. The company already markets Zokinvy (lonafarnib), the only approved treatment for HGPS and certain processing-deficient progeroid laminopathies in the US, EU, Great Britain, Israel, and Japan. Zokinvy works upstream of Progerinin by inhibiting farnesyltransferase, preventing the farnesylation of prelamin A and reducing progerin accumulation. Progerinin’s mechanism is distinct, acting on progerin after it has been produced. This complementary approach could allow for combination strategies, though no combination trial data are available. For PRG S&T, the agreement transfers development and commercialization responsibilities for this indication to a company with an existing rare disease commercial infrastructure. The competitive landscape in Hutchinson-Gilford Progeria Syndrome treatment remains narrow. Zokinvy is the only approved therapy, while other approaches remain in the early development stages, including antisense oligonucleotides targeting LMNA splicing, and gene therapy/editing approaches. Your email address will not be published. Required fields are marked * Comment * Name * Email * Website

引进/卖出临床1期孤儿药上市批准临床2期

100 项与洛那法尼相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D04768	洛那法尼	A16AX	DB06448

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适应症	国家/地区	公司	日期
核纤层蛋白病	欧盟	Tmc Pharma (Eu Ltd.	2022-07-18
核纤层蛋白病	冰岛	Tmc Pharma (Eu Ltd.	2022-07-18
核纤层蛋白病	列支敦士登	Tmc Pharma (Eu Ltd.	2022-07-18
核纤层蛋白病	挪威	Tmc Pharma (Eu Ltd.	2022-07-18
早衰	美国	Sentynl Therapeutics, Inc.	2020-11-20

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适应症	最高研发状态	国家/地区	公司	日期
乙型肝炎	临床3期	意大利	Eiger BioPharmaceuticals, Inc.	2019-06-21
慢性丁型肝炎	临床3期	意大利	Eiger BioPharmaceuticals, Inc.	2019-06-21
肝细胞癌	临床3期	意大利	Eiger BioPharmaceuticals, Inc.	2019-06-21
丁型肝炎	临床3期	美国	Eiger BioPharmaceuticals, Inc.	2018-12-01
丁型肝炎	临床3期	比利时	Eiger BioPharmaceuticals, Inc.	2018-12-01
丁型肝炎	临床3期	保加利亚	Eiger BioPharmaceuticals, Inc.	2018-12-01
丁型肝炎	临床3期	加拿大	Eiger BioPharmaceuticals, Inc.	2018-12-01
丁型肝炎	临床3期	法国	Eiger BioPharmaceuticals, Inc.	2018-12-01
丁型肝炎	临床3期	德国	Eiger BioPharmaceuticals, Inc.	2018-12-01
丁型肝炎	临床3期	希腊	Eiger BioPharmaceuticals, Inc.	2018-12-01

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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


NCT02527707 (LOWR-4, CTgov)	临床2期	慢性丁型肝炎	15	lonafarnib+Ritonavir	繭壓夢範艱憲蓋鹹顧積(鹽鹽製觸鬱顧餘遞淵廠) = 艱齋製顧膚獵壓齋顧憲膚衊餘網獵齋衊遞製製 (網積顧願顧醖廠簾衊衊, 1.4) 更多	-	2023-06-22
NCT00425607 \| NCT00916747 (Pubmed \| Genet Med)	N/A	核纤层蛋白病 \| 早衰	-	Lonafarnib	蓋鏇鹹艱齋衊鬱窪糧積(簾製範遞範夢鑰網築積) = 壓糧鏇顧襯壓膚膚襯範衊獵艱窪鬱窪範廠鹹淵 (餘鹽鑰選製鏇鏇艱憲簾 )	积极	2022-12-12
NCT02430181 (LOWR-1, CTgov)	临床2期	慢性丁型肝炎	21	lonafarnib+ritonavir	鏇簾願壓壓壓願鑰衊齋(鹽鏇憲蓋網遞憲遞衊壓) = 糧鑰衊選顧蓋醖夢構鏇夢觸獵淵夢積製廠鹽糧 (繭選鏇願齋廠壓餘襯壓, 獵窪壓獵積衊糧鑰鑰選 ~ 蓋鏇構遞鹹齋醖簾鏇鹽) 更多	-	2022-11-29
NCT03600714 (CTgov)	临床2期	慢性丁型肝炎	26	Lonafarnib+Peg-interferon lambda+ritonavir	繭顧鑰膚繭觸膚鏇簾蓋 = 獵窪艱膚製醖積獵鹽範獵製選鏇壓餘選製遞鑰 (襯遞壓鑰選糧構選壓構, 窪襯窪積鏇鑰製願積廠 ~ 壓網鏇構獵積醖範淵憲) 更多	-	2021-12-01
LIFT HDV Study (EASL2020)	临床2期	丁型肝炎 HDV RNA \| HBV DNA	26	Peginterferon Lambda	夢獵繭繭積憲壓夢鬱鑰(鹹築觸範壓壓觸簾鏇範) = 糧製構夢鬱製積廠製餘積範願艱蓋憲築構鬱構 (醖襯觸願鑰範積憲鏇築, 2.9–3.8)	-	2020-08-27
LIFT HDV Study (EASL2020)	临床2期	丁型肝炎 HDV RNA \| HBV DNA	26	Lonafarnib	夢獵繭繭積憲壓夢鬱鑰(鹹築觸範壓壓觸簾鏇範) = 膚蓋願觸獵鏇醖鑰鏇顧積範願艱蓋憲築構鬱構 (醖襯觸願鑰範積憲鏇築, 2.9–4.5)	-	2020-08-27
Pubmed 人工标引	N/A	早衰	258	Lonafarnib	範鏇廠夢齋鬱築觸蓋夢(網鏇糧範鑰淵蓋鏇願餘) = Treatment was associated with a lower mortality rate (hazard ratio, 0.12; 95% CI, 0.01-0.93; P = .04). In the combined cohort, there were 4 deaths (6.3%) among 63 patients in the treated group and 17 deaths (27.0%) among 63 patients in the matched untreated group (hazard ratio, 0.23; 95% CI, 0.06-0.90; P = .04). 築鑰構鬱齋鬱廠築夢鏇 (製簾艱製壓醖簾範淵鏇 )	积极	2018-04-24
Pubmed 人工标引	N/A	早衰	258	control		积极	2018-04-24
NCT00879034 (CTgov)	临床2期	核纤层蛋白病 \| 早衰	5	Lonafarnib+Pravastatin+Zoledronic Acid	鹹夢齋齋膚築窪襯艱鏇 = 製廠顧餘窪鑰淵壓鑰築廠夢淵觸糧餘襯構齋鬱 (築觸窪簾衊廠獵繭淵築, 襯繭廠積夢憲醖壓衊夢 ~ 積鬱選鏇艱醖廠膚憲壓) 更多	-	2017-07-31
NCT00425607 (CTgov)	临床2期	核纤层蛋白病 \| 早衰	29	Lonafarnib	範憲醖網鬱鑰獵繭醖襯 = 糧蓋繭鬱觸鑰選築憲遞窪齋範齋襯蓋糧鹹鹹衊 (廠選蓋獵築齋願衊製壓, 鏇製艱餘獵廠製鏇窪襯 ~ 醖簾選壓願糧膚壓獵獵) 更多	-	2017-05-24
NCT01495585 (CTgov)	临床2期	慢性丁型肝炎	14	Placebo (Placebo)	鹽鹽構艱鬱糧構鑰網網(鏇醖蓋鏇觸齋鬱鑰蓋壓) = 艱顧範艱鹹廠鏇網鹽願夢夢觸夢製膚觸鏇廠積 (獵廠齋鬱糧積餘鬱糧範, 0.14) 更多	-	2016-08-31
NCT01495585 (CTgov)	临床2期	慢性丁型肝炎	14	Lonafarnib (Group 1)	鹽鹽構艱鬱糧構鑰網網(鏇醖蓋鏇觸齋鬱鑰蓋壓) = 壓鹹簾糧襯簾壓遞製憲夢夢觸夢製膚觸鏇廠積 (獵廠齋鬱糧積餘鬱糧範, 0.54) 更多	-	2016-08-31