A Phase Ib/II Open-Label, Dose-Escalation, Safety, Pharmacokinetic, Pharmacodynamic and Efficacy Study of Bemcentinib Plus Pacritinib In Patients With Advanced Lung Adenocarcinoma

This is a Phase Ib/II, open-label, single institution dose-escalation, safety, pharmacokinetics, pharmacodynamic and efficacy study.

开始日期2024-12-27

申办/合作机构

University of Texas Health Science Center At San Antonio

[+1]

NCT05469178

/ Recruiting临床1/2期

Phase 1b/2a Safety and Tolerability Study of Bemcentinib with Pembrolizumab/carboplatin/pemetrexed in Subjects with Untreated Advanced or Metastatic Non-squamous Non-small Cell Lung Cancer (NSCLC) Without/with a STK11 Mutation

The primary purpose of this study is to determine the safety and tolerability of the combination of bemcentinib with chemo-immunotherapy (CIT) to identify the recommended phase 2 dose (RP2D) when administered as first line (1L) treatment in participants with locally advanced (Stage IIIb/IIIC) or metastatic (Stage IV) non-squamous NSCLC with no actionable mutations and to determine the anti-tumor activity of the combination of bemcentinib with CIT when administered as 1L treatment in participants with locally advanced (Stage IIIb/IIIc) or metastatic (Stage IV) non-squamous NSCLC with serine/threonine kinase 11 (STK11) mutation and no actionable mutations.

开始日期2023-03-06

申办/合作机构

BerGenBio ASA

CTIS2022-500363-12-00

/ Not yet recruiting临床2期IIT

Efficacy and Safety of AXL-Inhibitor bemcentinib for the Treatment of Moderate COVID-19 (AXL-SolidAct) - AXL-SolidAct

开始日期2022-09-27

申办/合作机构-

100 项与 Bemcentinib 相关的临床结果

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100 项与 Bemcentinib 相关的转化医学

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100 项与 Bemcentinib 相关的专利（医药）

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229

项与 Bemcentinib 相关的文献（医药）

2025-03-01·INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY

Bemcentinib enhances sensitivity to estrogen receptor inhibitors in breast cancer cells

Article

作者: Jin, Hyeon-Ok ; Ahn, Se Hee ; Kim, Gyeongmi ; Park, In-Chul ; Park, Chan Sub ; Kim, Hyunggee ; Park, Ki Soo ; Kim, Hyun-Ah ; Kim, Selim ; Seong, Min-Ki ; Jang, Se-Kyeong

Estrogen receptor (ER)-positive breast cancer accounts for a substantial proportion of breast cancer cases and is typically managed using ER inhibitors, such as tamoxifen and fulvestrant. However, the development of resistance to these therapies is a significant clinical challenge, and the improvement of therapeutic strategies is crucial. This study aimed to investigate the potential of bemcentinib, a well-known AXL inhibitor, to enhance the sensitivity of MCF7 breast cancer cells to 4-hydroxytamoxifen (4-OHT) and fulvestrant. Our findings revealed that bemcentinib effectively decreased S6K1 phosphorylation and synergistically induced cell death when used in combination with ER inhibitors. Bemcentinib treatment also unexpectedly activated STAT3, and inhibition of STAT3 enhanced cell death induced by bemcentinib and 4-OHT. Notably, the combination of bemcentinib and 4-OHT effectively induced cell death even in tamoxifen-resistant MCF7 cells (MCF7-TR), highlighting its potential to overcome tamoxifen resistance. Interestingly, AXL knockdown did not enhance the sensitivity to 4-OHT or affect S6K1 signaling in either MCF7 or MCF7-TR cells, suggesting that the sensitizing effect of bemcentinib through S6K1 inhibition may be independent of AXL expression. Our findings suggest that bemcentinib treatment, particularly in combination therapy, could be a promising strategy for improving treatment efficacy and overcoming tamoxifen resistance in ER-positive breast cancer.

2025-01-01·FEBS Journal

The AXL inhibitor bemcentinib overcomes microenvironment‐mediated resistance to pioglitazone in acute myeloid leukemia

Article

作者: Largeaud, Laetitia ; Bardet, Valérie ; Lefebvre‐Fortané, Anne‐Margaux ; Prost, Stéphane ; Calvo, Julien ; Guérineau, Hippolyte ; Lambert, Juliette ; Boudouin, Maèva ; Clauser, Sylvain ; Zhu, Jaja ; Rousselot, Philippe

Prognosis of acute myeloid leukemia (AML) remains poor especially in older patients who are ineligible for standard chemotherapy or have refractory disease. Here, we study the potential of Peroxisome Proliferator‐Activated Receptor (PPAR)‐γ agonist pioglitazone to improve the treatment of AML. We show that pioglitazone exerts an anti‐proliferative and anti‐clonogenic effect on AML cell lines KG‐1a, MOLM‐14 and OCI‐AML3 and on primary cultures from AML patients. However, co‐culture of AML cells with stromal cells mimicking the bone marrow microenvironment counteracts this effect, suggesting the existence of a stroma‐mediated resistance mechanism to pioglitazone. We show that pioglitazone treatment upregulates the receptor AXL in AML cells at the mRNA and protein level, allowing AXL to be phosphorylated by its ligand Gas6, which is secreted by the stroma. Addition of exogenous Gas6 or stromal cell conditioned medium also abolishes the anti‐proliferative effect of pioglitazone, with an increase in AXL phosphorylation observed in both conditions. Co‐incubation with the AXL inhibitor bemcentinib restored the anti‐leukemic activity of pioglitazone in the presence of stromal cells by reducing AXL phosphorylation to its baseline level. We also confirm that this resistance mechanism is PPAR‐γ‐dependent as stromal cells invalidated for PPAR‐γ are unable to inhibit the antileukemic effect of pioglitazone. Altogether, we suggest that pioglitazone treatment exerts an anti‐leukemic effect but concomitantly triggers a stroma‐mediated resistance mechanism involving the Gas6/AXL axis. We demonstrate that a combination of pioglitazone with an AXL inhibitor overcomes this mechanism in primary cultures and AML cell lines and exerts potent anti‐leukemic activity requiring further evaluation in vivo through murine xenograft pre‐clinical models.

2024-12-20·JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS

The promising impact of Bemcentinib and Repotrectinib on sleep impairment in Alzheimer’s disease

Article

作者: Ramezani, Fatemeh ; Ariaei, Armin

Alzheimer's disease (AD), the most prevalent neurodegenerative disease, demands effective medication to alleviate symptoms. This study focused on sleep impairment as an overt clinical symptom and tauopathy as a prominent molecular symptom of this disease. Multiple compounds from three biomolecule libraries (719 compounds; ChemDiv:366 - ChEMBL:180 - PubChem:173) were evaluated for potential binding affinity and safety using AutoDock Vina and pkCSM, respectively, resulting in the selection of four candidate compounds (Lestaurtinib, Repotrectinib, Bemcentinib, and Zotiraciclib). Due to the similarity of Repotrectinib and Bemcentinib binding sites to ATP, 300 ns Martini 3 coarse-grained molecular dynamics (MD) was performed on these two molecules and ATP by NAMD. The stability of tau protein in the presence of drugs was assessed using a 200 ns Martini 3 MD simulation. Binding site analysis discloses Bemcentinib and Repotrectinib as two inhibitors occupying most amino acids in binding with ATP. The RMSD and RMS average correlation results revealed protein containing Bemcentinib and Repotrectinib to have a more stable state compared to ATP in the first 220 ns simulation. There was only a single detachment of Bemcentinib, while Repotrictinib detached twice at the end of the simulation. Eventually, adding Bemcentinib and Repotrectinib to the enzyme-tau complex significantly increased the number of tau detachments during the 200 ns simulation. We report Bemcentinib and Repotrectinib, formerly prescribed for cancer, as potential inhibitors of the CK1 δ. Besides their high binding affinity compared to ATP, they can inhibit all ATP-binding sites and alter the tau binding stability.Communicated by Ramaswamy H. Sarma.

项与 Bemcentinib 相关的新闻（医药）

2025-03-06

·PRNewswire

TEPMETKO Continues to Strengthens its Position as a Leading METex14 Skipping NSCLC Therapy | DelveInsight

With increasing biomarker-driven cancer treatments, TEPMETKO benefits from growing adoption in precision oncology. Competition from other MET inhibitors like TABRECTA (capmatinib) exists, but TEPMETKO's once-daily dosing and efficacy profile offer differentiation. LAS VEGAS, March 6, 2025 /PRNewswire/ -- DelveInsight's " TEPMETKO Market Size, Forecast, and Market Insight Report" highlights the details around TEPMETKO, a kinase inhibitor indicated for the treatment of adult patients with metastatic NSCLC harboring MET exon 14 skipping alterations. The report provides product descriptions, patent details, and competitor products (marketed and emerging therapies) of TEPMETKO. The report also highlights the historical and forecasted sales from 2020 to 2034 segmented into 7MM [the United States, the EU4 (Germany, France, Italy, and Spain), the United Kingdom, and Japan]. EMD Serono's TEPMETKO (tepotinib) Overview TEPMETKO is a kinase inhibitor prescribed for adult patients with metastatic non-small cell lung cancer (NSCLC) carrying MET exon 14 skipping alterations. The active component is Tepotinib (as hydrochloride monohydrate), administered orally. Patients should be cautioned about the heightened risk of severe or fatal interstitial lung disease/pneumonitis, liver toxicity, and potential embryo-fetal toxicity, necessitating effective contraception during and shortly after treatment. Tepotinib specifically targets MET, including variants with exon 14 skipping mutations. It blocks HGF-dependent and independent MET phosphorylation, disrupting MET-driven signaling pathways. Additionally, at clinically relevant concentrations, Tepotinib inhibits melatonin 2 and imidazoline 1 receptors. In vitro studies show that it suppresses tumor cell proliferation, anchorage-independent growth, and migration of MET-dependent cancer cells. In mouse models with MET-driven tumors, including those with MET exon 14 skipping alterations, Tepotinib reduced tumor growth, sustained MET phosphorylation inhibition, and, in one case, decreased metastasis formation. The recommended dose of TEPMETKO is 450 mg taken orally once daily until disease progression or intolerable toxicity occurs. Patients should take it at the same time each day, swallowing tablets whole without chewing, crushing, or splitting them. If a dose is missed and less than eight hours remain until the next scheduled dose, patients should skip it. In cases of vomiting after taking TEPMETKO, the next dose should be taken at the usual time. Learn more about TEPMETKO projected market size for NSCLC @ TEPMETKO Market Potential Non-small cell lung cancer (NSCLC) is the most common type of lung cancer, accounting for 81% of all diagnosed cases. Early detection greatly improves outcomes, but diagnosing NSCLC and other lung cancers is challenging because their symptoms are often mistaken for common illnesses or the long-term effects of smoking. Consequently, 80% of NSCLC cases are already at advanced stages by the time they are identified, making treatment more difficult. Around 80% of EGFR mutations in NSCLC involve either exon 19 deletions or the exon 21 L858R substitution, both of which are classified as sensitizing mutations. Until the last decade, chemotherapy was the primary treatment for advanced and metastatic lung cancer. However, this changed in 2015 with the approval of the first immune checkpoint inhibitor (ICI), KEYTRUDA (pembrolizumab), as a second-line therapy for advanced cases. This was followed by TECENTRIQ (atezolizumab) in 2016. Both therapies were later approved for first-line treatment, broadening their use to a larger patient population. In 2020, the combination of OPDIVO (nivolumab) and ipilimumab also received approval as a first-line treatment for metastatic NSCLC. According to DelveInsight, the NSCLC market size across the 7MM is projected to grow from USD 30 billion in 2024, with a substantial CAGR through 2034. This growth is largely driven by the introduction of emerging therapies during the forecast period (2025–2034). Discover more about the NSCLC market in detail @ Non-small Cell Lung Cancer Market Report Emerging Competitors of TEPMETKO The NSCLC pipeline is very robust with the promising therapies such as Telisotuzumab vedotin (AbbVie), Patritumab deruxtecan (Daiichi Sankyo/AstraZeneca), Datopotamab deruxtecan (Daiichi Sankyo/AstraZeneca), Eftilagimod alpha (Immutep), BNT311/GEN1046 (acasunlimab) (Genmab), V940 (mRNA-4157) + Pembrolizumab (Moderna Therapeutics/Merck), Plinabulin + Docetaxel (BeyondSpring), Olomorasib (LY3537982) (Eli Lilly and Company), Zipalertinib (Cullinan Oncology/Taiho Pharma), Ceralasertib (AZD6738) (AstraZeneca), TEDOPI (EP-2101; IDM 2101; OSE-2101) (OSE Immuno-therapeutics), Sigvotatug vedotin (PF08046047) (Pfizer), ANKTIVA (N-803) (ImmunityBio), Aumolertinib/Almonertinib/HS-10206 (Jiangsu Hansoh Pharmaceutical), Niraparib (GSK), Savolitinib (AstraZeneca/Hutchison MediPharma), TRODELVY (Gilead Sciences), Pyrotinib (Jiangsu HengRui Medicine), Ociperlimab (BGB-A1217) (BieGene), Volrustomig (AstraZeneca), Gotistobart (BNT316/ONC-392) (OncoC4/BioNTech), Ivonescimab (AK112/SMT112) (Akeso Biopharma/Summit Therapeutics), ZYNYZ (retifanlimab/INCMGA00012) (Incyte/Macrogenics), Divarasib (GDC-6036) (Roche/Genentech), Tiragolumab (RG6058) (Roche), Sacituzumab Tirumotecan (Merck and Kelun-Biotech), JEMPERLI (dostarlimab/TSR-042) (GSK and AnaptysBio), Zongertinib (BI-1810631) (Boehringer Ingelheim), BAY 2927088 (Bayer), Serplulimab (HLX10) (Shanghai Henlius Biotech), Rilvegostomig (AZD2936) (AstraZeneca), MK-1084 (Merck, Taiho Pharmaceutical, and Astex), Domvanalimab (Arcus Biosciences and Gilead Sciences), OPDUALAG (nivolumab and relatlimab) (Bristol-Myers Squibb), Belrestotug + JEMPERLI (iTeos Therapeutics and GSK), Firmonertinib (ArriVent BioPharma), Sunvozertinib (DZD9008) (Dizal Pharmaceutical), Cobolimab (GSK), Livmoniplimab (AbbVie), Fianlimab (REGN3767) (Regeneron Pharmaceuticals), BNT327/PM8002 (Biotheus/BioNTech), HS-20117 (Hansoh BioMedical), IO102-IO103 + Pembrolizumab (IO Biotech), Naptumomab estafenatox (NeoTX Therapeutics/Active Biotech), FF-10832 (FUJIFILM Corporation), BNT116 (BioNTechSE/Regeneron Pharmaceuticals), CAN-2409 (Candel Therapeutics), Mecbotamab Vedotin (BA3011/CAB-AXL-ADC) (BioAtla), Bemcentinib (BGB 324/BGB-3234/R-428) (BerGenBio/Rigel Pharmaceuticals), DOVBLERON (taletrectinib/AB-106/IBI-344) (Nuvation Bio/Innovent Biologics/Daiichi Sankyo/Nippon Kayaku), Lifileucel (Iovance Biotherapeutics), IBI363 (Innovent Biologics), Sotevtamab (AB-16B5) (Alethia Biotherapeutics), Avutometinib (VS6766) (Verastem Oncology), Vebreltinib (APL-101) (Apollomics), LP-300 (Lantern Pharma), JNJ-90301900 (Johnson & Johnson Innovative Medicine), AMG 193 (Amgen), Luveltamab tazevibulin (Sutro Biopharma), PRT3789 (Prelude Therapeutics), Disitamab vedotin (Seagen), PADCEV (enfortumab vedotin) (Astellas Pharma), RP1 (Replimune), TIVDAK (tisotumab vedotin) (Seagen), Zanidatamab (Jazz Pharmaceuticals), Utidelone injectable (UTD1) (Beijing Biostar Pharmaceuticals), REGN5093-M114 (Regeneron Pharmaceuticals), SLC-391 (SignalChem Lifesciences), fulzerasib (GenFleet), Davutamig (REGN5093) (Regeneron Pharmaceuticals), TAS3351 (Taiho Oncology), H002 (RedCloud Bio), JIN-A02 (J INTS BIO), FWD1509 (Forward Pharma), Sabestomig (AZD7789) (AstraZeneca), Sasanlimab (Pfizer), Selvigaltin (GB1211) (Galecto Biotech), Vepafestinib Helsinn (Healthcare/Taiho Pharmaceutical), EP0031 (A400/ KL590586) (Ellipses Pharma/Kelun-Biotech), Pamvatamig (MCLA-129) (Merus), Zidesamtinib (NVL-520) (Nuvalent), NVL-655 (Nuvalent), RMC-4630 (Revolution Medicines), REQORSA (quaratusugene ozeplasmid) (Genprex), PDC*lung01 (PDC*line Pharma), Evalstotug (BA3071) (BioAtla and BeiGene), PT-112 (Promontory Therapeutics), MRT-2359 (Monte Rosa Therapeutics), GAIA-102 (GAIA BioMedicine), Rigosertib (Traws Pharma), HMBD-001 (Hummingbird Bioscience), PLB1004 (Avistone Biotechnology), ANS03 (Avistone Biotechnology), MYTX-011 (Mythic Therapeutics), A166 (Sichuan Kelun-Biotech Bio-pharmaceutical), Atamparib (BN-2397) (Ribon Therapeutics), DELTACEL (KB-GDT-01) (Kiromic BioPharma), Carotuximab (ENV-105) (Kairos Pharma), YL202 (MediLink Therapeutics), and others. To know more about the number of competing drugs in development, visit @ TEPMETKO Market Positioning Compared to Other Drugs Key Milestones of TEPMETKO In February 2024, the FDA granted traditional approval to TEPMETKO for adult patients with metastatic NSCLC harboring MET exon 14 skipping alterations. In February 2022, the EC approved TEPMETKO as monotherapy for the treatment of adult patients with advanced NSCLC harboring alterations leading to METex14 skipping who require systemic therapy following prior treatment with immunotherapy and/or platinum-based chemotherapy. In February 2021, Merck announced that the US FDA has approved TEPMETKO following priority review for the treatment of adult patients with metastatic NSCLC harboring MET exon 14 skipping alterations. This indication was approved under accelerated approval based on ORR and DOR. In October 2020, TEPMETKO received ODD for treating NSCLC with MET genomic tumor aberrations In March 2020, EMD Serono (the biopharmaceutical business of Merck KGaA), announced that the MHLW approved TEPMETKO for the treatment of patients with unresectable, advanced, or recurrent NSCLC with METex14 skipping alterations. In September 2019, the US FDA granted BTD for tepotinib in patients with metastatic NSCLC harboring METex14 skipping alterations who progressed following platinum-based cancer therapy Discover how TEPMETKO is shaping the NSCLC treatment landscape @ TEPMETKO NSCLC TEPMETKO Market Dynamics TEPMETKO competes in a growing but highly specialized market where MET-targeted therapies are gaining traction due to their efficacy in addressing MET-altered tumors. The market for MET inhibitors is expanding as precision oncology advances and molecular diagnostics become more widely available, enabling better identification of patients who would benefit from targeted treatments like TEPMETKO. A key factor shaping TEPMETKO's market dynamics is competition. It directly competes with Novartis' TABRECTA (capmatinib), another MET inhibitor approved for the same indication. While TEPMETKO offers the advantage of once-daily dosing compared to TABRECTA's twice-daily regimen, both drugs have similar efficacy profiles, making physician and patient preference an important differentiator. Additionally, broader competition from next-generation MET inhibitors and combination therapies in clinical trials could impact TEPMETKO's long-term market position. Regulatory approvals and market access play a crucial role in TEPMETKO's adoption. The drug has been approved in multiple regions, including the U.S., Europe, and Japan, but reimbursement and pricing strategies vary by market. Payer policies, along with the cost-benefit analysis of MET inhibitors compared to other targeted therapies, influence prescription trends. Furthermore, real-world evidence and post-marketing studies will be critical in demonstrating TEPMETKO's sustained effectiveness and safety, which could support expanded indications and increased market penetration. Looking ahead, the MET inhibitor market is expected to grow with advances in biomarker-driven therapy, further refining patient selection. TEPMETKO's success will depend on continued clinical development, potential label expansions, and strategic partnerships to strengthen its competitive edge. As new entrants emerge, Merck KGaA's ability to differentiate TEPMETKO through combination strategies or enhanced formulations may determine its long-term sustainability in this evolving landscape. Dive deeper to get more insight into TEPMETKO's strengths & weaknesses relative to competitors @ TEPMETKO Market Drug Report Table of Contents Related Reports Non-small Cell Lung Cancer Market Non-small Cell Lung Cancer Market Insights, Epidemiology, and Market Forecast – 2034 report deliver an in-depth understanding of the disease, historical and forecasted epidemiology, as well as the market trends, market drivers, market barriers, and key NSCLC companies including Daiichi Sankyo, AstraZeneca, Gilead Sciences, BieGene, AbbVie, Roche, Merck, Novartis, Pfizer, Takeda Pharmaceuticals, Eli Lilly, BerGenBio, GlaxoSmithKline, Duality biologics, among others. Non-small Cell Lung Cancer Pipeline Non-small Cell Lung Cancer Pipeline Insight – 2025 report provides comprehensive insights about the pipeline landscape, pipeline drug profiles, including clinical and non-clinical stage products, and the key non-small cell lung cancer companies, including BridgeBio Pharma, Daiichi Sankyo, EMD Serono, Merck, BridgeBio Pharma, Abbvie, Pfizer, Eli Lilly and Company BioNTech SE, Shenzhen TargetRx, Taiho Pharmaceutical, Chong Kun Dang, Bristol Myers Squibb, Innovent Biologics, Xuanzhu Biopharmaceutical, Bayer, GeneScience Pharmaceuticals, InventisBio, Apollomics, Imugene, Ono Pharmaceutical, Pierre Fabre, Jiangsu Hengrui Medicine Co., Bristol-Myers Squibb, Surface Oncology, Inhibrx, Sinocelltech, Mirati Therapeutics, REVOLUTION Medicines, Yong Shun Technology Development, Iovance Biotherapeutics, Galecto Biotech, among others. C-MET Metastatic Non-small Cell Lung Cancer Market C-MET Metastatic Non-small Cell Lung Cancer Market Insights, Epidemiology, and Market Forecast – 2034 report deliver an in-depth understanding of the disease, historical and forecasted epidemiology, as well as the market trends, market drivers, market barriers, and key C-MET mNSCLC companies, including Novartis, Merck, EMD Serono, AbbVie, Regeneron Pharmaceuticals, Mythic Therapeutics, Apollomics, Johnson & Johnson Innovation, Haihe Biopharma, among others. C-MET Non-small Cell Lung Cancer Pipeline C-MET Non-small Cell Lung Cancer Pipeline Insight – 2025 report provides comprehensive insights about the pipeline landscape, pipeline drug profiles, including clinical and non-clinical stage products, and the key C-MET non-small cell lung cancer companies, including AbbVie, Janssen Research & Development, Beijing Pearl Biotechnology Limited Liability Company, Novartis, among others. About DelveInsight DelveInsight is a leading Business Consultant and Market Research firm focused exclusively on life sciences. It supports pharma companies by providing comprehensive end-to-end solutions to improve their performance. Get hassle-free access to all the healthcare and pharma market research reports through our subscription-based platform PharmDelve . Contact Us Shruti Thakur [email protected] +14699457679 Logo: SOURCE DelveInsight Business Research, LLP WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

上市批准免疫疗法优先审批

2025-03-05

·药学进展

学科前沿 | 复旦大学郁金泰教授团队联合袁鹏教授团队、中科院上海有机化学研究所刘聪教授团队在帕金森病发病机制研究方面取得进展

“ 点击蓝字关注我们复旦大学郁金泰教授团队联合袁鹏教授团队、中科院上海有机化学研究所生物与化学交叉研究中心刘聪教授团队在帕金森病发病机制研究方面取得进展 PPS 在国家自然科学基金项目（批准号：82271471、82401676、92249305）等资助下，复旦大学附属华山医院郁金泰教授团队联合复旦大学脑科学转化研究院袁鹏教授团队、中科院上海有机化学研究所生物与化学交叉研究中心刘聪教授团队在帕金森病发病机制研究方面取得进展。研究成果以“神经元FAM171A2介导α-突触核蛋白纤维摄取并促进帕金森病发生（Neuronal FAM171A2 mediates α-synuclein fibril uptake and drives Parkinson's disease）”为题，于2025年2月20日在线发表于《科学》（Science）杂志，论文链接：https://www-science-org.libproxy1.nus.edu.sg/doi/10.1126/science.adp3645。帕金森病（Parkinson's disease, PD）是第二常见的神经退行性疾病，我国65岁以上老年人群中帕金森病患病率为1.7%，到2030年，我国帕金森病患者数预计将达500万，几乎占到全球患者数的一半。既往研究发现α-突触核蛋白在病理条件下会发生错误折叠并聚集形成病理性α-突触核蛋白，破坏神经元功能并导致其死亡，是PD的关键致病蛋白。这些致病蛋白还会像“种子”一样播散，入侵邻近神经元，募集神经元内α-突触核蛋白单体发生错误折叠，形成更多的致病“种子”。这些致病“种子”可以在神经元间传播，当传播到中脑黑质区域时，可导致多巴胺能神经元死亡，从而出现动作迟缓、静止性震颤、肌强直等PD运动症状。但目前病理性α-突触核蛋白在神经元间传播机制尚不清楚，临床仍然缺乏有效干预手段。研究团队首先通过大规模人群的全基因组关联分析，发现FAM171A2是PD风险基因；并基于PD患者临床样本分析发现，患者大脑中FAM171A2蛋白含量增高，且FAM171A2含量越高的患者，其脑内病理性α-突触核蛋白含量也越高。进一步研究发现在神经元细胞膜上，FAM171A2可选择性的结合病理性α-突触核蛋白，并携带其进入到神经元中，诱导神经元内单体形式的α-突触核蛋白发生错误折叠，造成神经元死亡和其在神经元间的传播。团队随后研究证实敲除小鼠神经元上FAM171A2，可以有效控制小鼠帕金森样症状的进展。基于前述发现，研究团队利用人工智能的蛋白结构预测和虚拟筛选技术，从7000余种药物中成功筛选出候选小分子bemcentinib，并在体外实验和动物实验证实该小分子可有效抑制FAM171A2蛋白和病理性α-突触核蛋白结合，并抑制多巴胺能神经元对病理性α-突触核蛋白的摄取。该研究发现了神经元上病理性α-突触核蛋白潜在膜受体FAM171A2蛋白，揭示了FAM171A2蛋白是促进病理性α-突触核蛋白传播的关键，筛选出FAM171A2有效阻断剂bemcentinib是治疗PD的候选小分子。该研究结果为PD的治疗提供了潜在新靶点和新思路。文章来源：国家自然科学基金委员会美编排版：陈鑫茹文章审核：周碧远陈鑫茹罗琪【免责声明】以上内容来源于互联网，不代表本平台立场或观点；如有侵犯作者著作权，请及时与我们联系（Tel：025-83271227，或直接在微信平台留言），我们将及时更正或删除。《药学进展》杂志由国家教育部主管、中国药科大学和中国药学会共同主办，中国科技核心期刊（中国科技论文统计源期刊）。刊物以反映药学科研领域的新方法、新成果、新进展、新趋势为宗旨，以综述、评述、行业发展报告为特色，以药学学科进展、技术进展、新药研发各环节技术信息为重点，是一本专注于医药科技前沿与产业动态的专业媒体。《药学进展》注重内容策划、加强组稿约稿、深度挖掘、分析药学信息资源、在药学学科进展、科研思路方法、靶点机制探讨、新药研发报告、临床用药分析、国际医药前沿等方面初具特色；特别是医药信息内容以科学前沿与国家战略需求相合，更加突出前瞻性、权威性、时效性、新颖性、系统性、实战性。根据最新统计数据，刊物篇均下载率连续三年蝉联我国医药期刊榜首，复合影响因子1.216，具有较高的影响力。《药学进展》编委会由国家重大专项化学药总师陈凯先院士担任主编，编委由新药研发技术链政府监管部门、高校科研院所、制药企业、临床医院、CRO、金融资本及知识产权相关机构近两百位极具影响力的专家组成。联系《药学进展》↓↓↓ 编辑部官网：pps.cpu.edu.cn；邮箱：yxjz@163.com；电话：025-83271227。欢迎投稿、订阅！往期推荐聚焦“兴药为民·2023生物医药创新融合发展大会”“兴药为民·2023生物医药创新融合发展大会”盛大启幕！院士专家齐聚杭城，绘就生物医药前沿赛道新蓝图“兴药强刊”青年学者论坛暨《药学进展》第二届青年编委会议成功召开“兴药为民·2023生物医药创新融合发展大会”路演专场圆满收官！校企合作新旅程已启航我知道你在看哟

申请上市

2025-02-26

·Endpoints

Harbour BioMed inks deal up to $395M; ORIC refines plans for two drugs

Plus, news about Idorsia, Enveda, Zymeworks, BerGenBio and Ignota Labs: Harbour BioMed does another deal: The Shanghai-based biotech’s subsidiary, called HBM Alpha Therapeutics, inked a pact with an undisclosed company for up to $395 million in upfront fees and biobucks, plus the potential for a minority stake. The undisclosed partner also gets exclusive ex-China global rights to an antibody known as HAT001/HBM9013 for congenital adrenal hyperplasia (CAH) and other rare endocrine disorders. HBMAT raised a seed round of undisclosed size in January 2023, and Harbour did a NewCo deal for an anti-TSLP antibody with Windward Bio last month. — Kyle LaHucik ORIC ‘refines’ development plans for two drugs: The ORIC-944 program is set to start a Phase 3 trial in the first half of 2026 looking at patients with metastatic castration-resistant prostate cancer. Its ORIC-114 candidate is expected to begin registrational trials sometime in 2026 in the first-line lung cancer setting. Its stock $ORIC was up about 13% on Wednesday morning. — Max Gelman Idorsia’s big updates: The Swiss drugmaker said an undisclosed party opted not to move forward with a deal for the global rights to Idorsia’s experimental hypertension drug, called aprocitentan, but it will keep the $35 million exclusivity fee that it got in December. Meanwhile, Idorsia and Viatris adjusted the terms of their collaboration for selatogrel and cenerimod, with Idorsia contributing $100 million less toward development while losing $250 million in potential milestone payments from Viatris. It is also restructuring its debt and getting new funding . — Kyle LaHucik Sanofi backs Enveda with $20M: The French pharma giant is joining the Series C of the Colorado biotech, which mines plant chemistry to find new drugs. The Series C now totals $150 million, up from the $130 million disclosed in November . — Kyle LaHucik Zymeworks’ $14M milestone: The company received the payment from GSK from a bispecific antibody deal they inked in 2016 and then expanded in 2019. — Jaimy Lee BerGenBio discontinues lung cancer study, to seek strategic alternatives: The company was evaluating whether bemcentinib, an AXL kinase inhibitor, could treat patients with first-line non-squamous non-small cell lung cancer in combination with standard of care. Patients also needed to have a mutation of the STK11 gene. In a statement, CEO Olav Hellebø said the results were not strong enough for BerGenBio to obtain additional financing and is now looking for a merger, sale or other transaction. — Max Gelman Ignota Labs closes £5.5M seed round: The startup’s goal is to “turn around failed drugs” using AI, acquiring assets from bigger companies that stopped being developed and then testing them in new clinical trials. Its first asset is a PDE9A inhibitor, which the company says has potential in cardiovascular, metabolic and neurodegenerative diseases. — Max Gelman

引进/卖出抗体药物偶联物

100 项与 Bemcentinib 相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D11438	Bemcentinib	-	DB12411

研发状态

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
转移性非鳞状非小细胞肺癌	临床2期	美国	BerGenBio ASA	2023-03-06
转移性非鳞状非小细胞肺癌	临床2期	法国	BerGenBio ASA	2023-03-06
转移性非鳞状非小细胞肺癌	临床2期	希腊	BerGenBio ASA	2023-03-06
转移性非鳞状非小细胞肺癌	临床2期	匈牙利	BerGenBio ASA	2023-03-06
转移性非鳞状非小细胞肺癌	临床2期	意大利	BerGenBio ASA	2023-03-06
转移性非鳞状非小细胞肺癌	临床2期	波兰	BerGenBio ASA	2023-03-06
转移性非鳞状非小细胞肺癌	临床2期	西班牙	BerGenBio ASA	2023-03-06
新型冠状病毒感染	临床2期	印度	BerGenBio ASA	2020-10-20
新型冠状病毒感染	临床2期	南非	BerGenBio ASA	2020-10-20
转移性胰腺癌	临床2期	美国	BerGenBio ASA	2019-01-03

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临床结果

适应症

分期

评价

查看全部结果

研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT02424617 (CTgov)	临床1/2期	非小细胞肺癌	40	Bemcentinib (Phase 1- Run in Arm (Bemcentinib Monotherapy))	蓋遞餘淵顧齋廠網鬱構(鬱窪願壓鬱觸膚醖淵積) = 壓蓋觸衊醖鏇艱獵構築網齋積艱構網築夢鏇鹹 (鹹蓋範餘築窪鹹膚鏇憲, 醖遞壓鹹鏇窪鏇鹽繭顧 ~ 夢構簾鏇衊構窪廠糧觸) 更多	-	2025-02-26
				Erlotinib+Bemcentinib (Phase 1- Arm A (Bemcentinib + Erlotinib))	蓋遞餘淵顧齋廠網鬱構(鬱窪願壓鬱觸膚醖淵積) = 築簾願餘觸積醖願網範網齋積艱構網築夢鏇鹹 (鹹蓋範餘築窪鹹膚鏇憲, 蓋襯築醖築餘齋壓襯憲 ~ 鬱壓網壓構鹹廠艱觸壓) 更多
NCT06469138 (8479217, CTgov)	临床1期	急性髓性白血病 \| 新型冠状病毒感染 \| 恶性间皮瘤 ... 更多	6	Bemcentinib	構醖糧簾願窪鏇糧鏇製(廠願選鏇憲艱淵鏇積築) = 鏇遞積簾繭獵艱醖壓選蓋襯築襯顧憲願簾繭遞 (淵衊艱夢構廠醖獵憲壓, 窪繭遞淵顧鑰窪製觸蓋 ~ 淵鏇膚餘襯齋淵製艱齋) 更多	-	2025-01-29
NCT04890509 (CTgov)	临床2期	新型冠状病毒感染	115	SoC	選網範遞蓋製繭構顧醖(膚鬱顧艱夢窪鹽齋糧衊) = 襯範簾遞觸鏇網鏇鬱襯範襯顧夢積憲願鹹餘鹽 (獵襯廠襯糧選餘艱齋積, 選範顧憲夢餘鹽網鹽餘 ~ 窪壓構願簾繭製鹹餘築) 更多	-	2024-10-16
NCT02488408 (BGBC003, ASH2023)	临床1/2期	急性髓性白血病	32	Bemcentinib + Low-dose Cytarabine	鹽夢願齋積襯鑰膚鏇夢(醖觸積範範餘鏇鹹願獵) = 憲獵選網窪鹹網襯構製齋觸壓艱夢襯鹽窪窪鏇 (構鹹鏇遞蓋觸願窪襯觸 ) 更多	-	2023-12-09
NCT03649321 (CTgov)	临床1/2期	转移性胰腺癌	9	Nab-paclitaxel+gemcitabine+cisplatin+Bemcentinib (Phase 1b)	鹹憲鑰壓範壓鏇窪鹽夢(鬱衊遞衊襯獵膚遞壓鬱) = 鬱襯鑰憲積襯鑰鹽顧齋淵鹽醖鹹鹽膚膚醖製艱 (廠壓選鏇鹽顧廠糧顧鏇, 製窪襯簾獵鬱襯蓋糧繭 ~ 積糧醖範網鏇憲醖廠蓋) 更多	-	2023-11-09
				Nab-paclitaxel+gemcitabine+Bemcentinib (Phase 2)	鹹憲鑰壓範壓鏇窪鹽夢(鬱衊遞衊襯獵膚遞壓鬱) = 齋顧鬱糧繭顧蓋餘顧觸淵鹽醖鹹鹽膚膚醖製艱 (廠壓選鏇鹽顧廠糧顧鏇, 襯鑰願鑰壓繭壓壓艱觸 ~ 鬱艱顧夢艱觸襯窪遞壓) 更多
NCT03184571 (BGBC008, ESMO 12023 \| ESMO 22023) 人工标引	临床2期	非小细胞肺癌二线	99	Bemcentinib + Pembrolizumab	壓膚廠淵顧鏇蓋膚網網(遞淵齋獵願網艱鬱獵窪) = 積餘網夢構糧鏇繭觸窪遞築鏇願製鹽齋顧鑰襯 (窪衊鬱鏇艱鑰齋獵鑰遞 ) 更多	积极	2023-10-23
				Bemcentinib + Pembrolizumab (AXL TPS > 5)	壓膚廠淵顧鏇蓋膚網網(遞淵齋獵願網艱鬱獵窪) = 鬱廠齋簾獵鬱餘衊觸憲遞築鏇願製鹽齋顧鑰襯 (窪衊鬱鏇艱鑰齋獵鑰遞 ) 更多
NCT02872259 (BGBIL006, ESMO 12023 \| ESMO 22023) 人工标引	临床1/2期	转移性黑色素瘤	68	Bemcentinib+PembrolizumabPem or D/TDabrafenibTrametinib (Bemcentinib+Pembrolizumab or Dabrafenib/Trametinib)	構範網鏇簾繭蓋膚壓鏇(憲餘鑰壓遞製糧選夢艱) = 願壓範醖衊鏇襯膚鏇襯顧選醖蓋繭壓願鏇壓餘 (選衊簾繭淵築蓋鏇獵膚 ) 更多	不佳	2023-10-21
				PembrolizumabPem or D/TDabrafenibTrametinib (Pembrolizumab or Dabrafenib/Trametinib)	-
NCT03654833 (MiST3, ASCO 12023 \| ASCO 22023) 人工标引	临床2期	间皮瘤	26	Pembrolizumab+Bemcentinib	鹽膚簾淵淵夢繭繭衊簾(獵鹹築餘簾窪構鬱範衊) = 鹽衊築醖顧觸齋齋窪醖構選齋糧獵築憲餘餘顧 (鹹築鏇構鑰蓋築鹹鏇壓, 29.2 ~ 63.4) 更多	积极	2023-05-26
NCT02922777 (ASCO2022) 人工标引	临床1期	非小细胞肺癌一线	21	Docetaxel+Bemcentinib	淵網觸網淵構簾廠窪淵(積襯鏇襯鏇簾餘鹽廠廠) = 60 mg/m2 docetaxel plus 200 mg bemcentinib daily 鏇鹹製淵鹹鬱衊積製鏇 (觸鑰構壓夢壓膚鏇願糧 ) 更多	积极	2022-06-02
NCT02488408 (BGBC003, EHA2022) 人工标引	临床2期	急性髓性白血病	22	Cytarabine+Bemcentinib	膚膚膚鏇遞繭範襯糧齋(廠鏇窪襯願廠醖襯簾膚) = 觸蓋網齋繭構網鬱鏇衊簾蓋蓋鏇衊範醖壓蓋醖 (繭艱鬱願夢選壓憲鑰鏇 ) 更多	积极	2022-05-12
				Cytarabine+Bemcentinib (in 1st relapse)	膚膚膚鏇遞繭範襯糧齋(廠鏇窪襯願廠醖襯簾膚) = 鹹壓願襯衊觸觸餘糧壓簾蓋蓋鏇衊範醖壓蓋醖 (繭艱鬱願夢選壓憲鑰鏇 ) 更多