A Phase 1 Study of Fosbretabulin in Combination With Everolimus in Neuroendocrine Tumors (Grades 1-3) That Have Progressed After at Least One Prior Regimen for Metastatic Disease

This is a single center, open label, phase I study involving grade I-III gastroenteropancreatic neuroendocrine tumors, consisting of a dose escalation Part A followed by an expansion cohort Part B. On Part A Patients will be treated with daily oral everolimus. Fosbretabulin will be administered IV either q3 weekly or q weekly based on PO CRM cohort. Part B: Once the investigators have established an MTD in Part A, the investigators will be treating 15 more patients at that dose combination. The primary and secondary objectives of the expansion cohort will be similar to Part A of the study, i.e., to establish a safety profile of the experimental drug combination and to collect and assess efficacy data. Patients will be treated with concurrent everolimus and fosbretabulin for 12 weeks.

开始日期2017-03-06

申办/合作机构

University of Kentucky

NCT01701349

/ Withdrawn临床3期

A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety and Efficacy of Fosbretabulin Tromethamine (CA4P) in Combination With Paclitaxel and Carboplatin in Anaplastic Thyroid Carcinoma (FACT2)

This is a multicenter, double-blind, placebo-controlled, randomized study of fosbretabulin given with chemotherapy (paclitaxel and carboplatin) compared to placebo given with chemotherapy (paclitaxel and carboplatin) in subjects with anaplastic thyroid cancer (ATC). The primary objective of the study is to determine overall survival. A maximum of 300 subjects will be recruited from approximately 75 multinational sites of which approximately 35 will be located in the United States.

开始日期2015-03-01

申办/合作机构

Oncotelic Therapeutics, Inc.

NCT02279602

/ Completed临床2期

Rollover for Study OX4218s, A P2 Study to Investigate Safety and Activity of Fosbretabulin Tromethamine in the Treatment of Well-Differentiated, Low-to-Intermediate-Grade Unresectable, Recurrent or Metastatic PNET or GI-NET With Elevated Biomarkers

Subjects achieving a clinical response in study OX4218s with a biomarker reduction or symptom response are eligible to enroll in this rollover study to continue once every three weeks fosbretabulin infusions for up to one year.

开始日期2014-12-01

申办/合作机构

Oncotelic Therapeutics, Inc.

100 项与康普瑞丁磷酸二钠相关的临床结果

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100 项与康普瑞丁磷酸二钠相关的转化医学

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100 项与康普瑞丁磷酸二钠相关的专利（医药）

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617

项与康普瑞丁磷酸二钠相关的文献（医药）

2026-06-01·MAGNETIC RESONANCE IN MEDICINE

Dynamic Contrast Enhanced—Magnetic Resonance Fingerprinting ( DCE ‐ MRF ) Improves Detection of Induced Vascular Perfusion Reduction in a Mouse Breast Cancer Model

Article

作者: Mark A. Griswold ; Mark D. Pagel ; Michael Kavran ; Bernadette O. Erokwu ; Christina J. MacAskill ; Gopalakrishnan Ramamurthy ; Chetan B. Dhakan ; Guanhua Wang ; Barbara J. Schiemann ; Chunying Wu ; Xin Yu ; Andrew Dupuis ; William P. Schiemann ; Chris A. Flask ; Yilun Sun ; Yuran Zhu

ABSTRACT:

Purpose:

Dynamic contrast‐enhanced MRI (DCE‐MRI) can assess tumor perfusion using pharmacokinetic models. However, poor DCE‐MRI reproducibility from reliance on conventional T 1 ‐weighted MRI has limited clinical translation. We evaluated whether Dynamic Contrast Enhanced‐Magnetic Resonance Fingerprinting (DCE‐MRF), which directly generates quantitative T 1 relaxation time constant maps, provides improved precision and statistical power for detecting treatment‐induced vascular changes compared to conventional DCE‐MRI.

Methods:

Twenty female mice bearing orthotopic 4 T1 breast tumors were randomly assigned to DCE‐MRF ( n = 12) or conventional DCE‐MRI ( n = 8) cohorts. Both methods acquired matched spatial and temporal resolution (23‐s) T 1 measurements at baseline, 3 h, and 48 h post‐treatment with combretastatin A4 phosphate (120 mg/kg), a known vascular disrupting agent. Perfusion assessments were obtained with a pharmacokinetic Linear Reference Region Model ( RKtrans and kep,T ) and model‐independent initial area under the curve assessments and compared using Wilcoxon signed‐rank tests and Hedges' g effect sizes.

Results:

DCE‐MRF demonstrated 1.3‐to‐5.1‐fold larger effect sizes for RKtrans across all regions and timepoint comparisons, and 1.3‐to‐1.9‐fold larger effect sizes for tumor rim kep,T compared to conventional DCE‐MRI. RKtrans and kep,T at 3 h post‐treatment in all regions, detected significant vascular recovery for whole tumor RKtrans and both whole tuomor and tumor rim for kep,T at 48 h, whereas DCE‐MRI only detected significant changes at 3 h.

Conclusions:

DCE‐MRF's improved measurement precision and increased effect size translates directly to enhanced statistical power for detecting treatment‐induced vascular changes, positioning it as a more reproducible tumor perfusion assessment for animal models and eventually cancer patients.

2026-06-01·CARBOHYDRATE RESEARCH

Enzymatic depolymerization, structural characterization, and anticoagulant activity evaluation of chondroitin sulfate A oligosaccharides

Article

作者: Li, Rongfeng ; Li, Kaiqiang ; Xing, Ronge ; Zhang, Chen ; Liu, Yuanjie ; Li, Pengcheng ; Liu, Song ; Yu, Huahua

Chondroitin sulfate (CS) polysaccharides exhibit intrinsic structural heterogeneity, limiting precise studies of their bioactivities and therapeutic applications. To obtain homogeneous CS oligosaccharides and elucidate structure-activity relationships, we developed a controlled enzymatic method for preparing well-defined chondroitin sulfate A (CSA) oligosaccharides and investigated their chain length-dependent anticoagulant mechanisms. Herein, hyaluronidase was used to depolymerize CSA and subsequently purified by sequential ultrafiltration and anion-exchange chromatography, yielding CSA oligosaccharide fractions (CSA4, CSA6, CSA8, CSA10 and CSA12). Their structures were confirmed by NMR spectroscopy and mass spectrometry. In vitro anticoagulation assays showed significant chain-length dependence: longer oligomers (CSA8, CSA10 and CSA12) profoundly prolonged activated partial thromboplastin time (APTT) and thrombin time (TT), suggesting potentiation of endogenous serine protease inhibitors. However, shorter oligomers (CSA4 and CSA6) just selectively prolonged prothrombin time (PT), indicating extrinsic pathway modulation. This work provides a reliable method for preparing CSA oligosaccharides and establishes a molecular foundation for developing safer, predictable CS-based anticoagulants.

2026-02-01·EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY

Design, synthesis, and biological evaluation of 2-(benzylthio)-5-(indol-3-yl)-1,3,4-oxadiazole derivatives as tubulin polymerization inhibitors with potential anti-cancer effects

Article

作者: You, Jie ; Xie, Qing ; Shi, Jing-Yi ; Man, Ruo-Jun ; Dai, Hong ; Yang, Bing ; Zhu, Hai-Liang

Thirty new 2-(benzylthio)-5-(indol-3-yl)-1,3,4-oxadiazole derivatives were designed, synthesized, and evaluated as tubulin inhibitors against cancers. Some target compounds showed relatively strong anti-proliferative activity against HepG2, HeLa, MCF-7, and A549 cells. Among them, the top hit, compound C21, yielded an IC₅₀ value of 0.08 μM against HeLa cells, exhibiting lower cytotoxicity compared to 293T cells. Tubulin polymerization inhibition assay indicated that the inhibitory activity of compound C21 (IC₅₀: 1.59 ± 0.66 μM) was stronger than that of Colchicine (IC₅₀: 2.52 ± 0.23 μM). Mechanism studies demonstrated that compound C21 could arrest cell cycle at the G2/M phase and induce tumor cell apoptosis in a dose- and time-dependent manner. The confocal imaging further demonstrated that compound C21 could inhibit tubulin polymerization, similar to Colchicine. Moreover, compound C21 showed excellent in vivo anti-tumor potency in a human cervical cancer xenograft mouse model with an inhibitory rate of 80.51 %, which was better than the CA-4P group (49.22 %) and the lower dose group (69.52 %). Furthermore, the docking simulation visualized the possible binding pattern of compound C21 into tubulin. Finally, the information provided in this study will be helpful for the future development of tubulin-related anti-cancer drugs.

项与康普瑞丁磷酸二钠相关的新闻（医药）

2026-04-28

·砌块化学

综述｜1,2,4‑噁二唑的生物等排体

1,2,4‑噁二唑作为酯/酰胺的水解稳定生物电子等排体，具备刚性结构、可调理化性质，已应用于抗癌、抗菌、抗病毒等多领域药物研发，通过QSAR、分子对接、虚拟筛选等方式，优化出多款高活性的候选分子，部分已进入临床前研究，是极具潜力的药物优势骨架。 DOI：10.1016/j.ejmech.2025.117935; DOI：10.1002/cmdc.202200638. 核心生物等排替换应用羧酸：解决羧酸低亲脂性、酰基葡萄糖醛酸毒性代谢问题；酯：解决酯体内易水解缺陷，作用时长显著延长；酰胺：提升代谢稳定性与靶点选择性；异硫脲：降低毒性，H3受体拮抗活性提升7 倍；哌嗪 / 吗啉：消除N‑亚硝基毒性代谢风险；噻唑 / 恶唑烷酮：保留抗菌活性，优化结合模式。药理活性全景抗癌活性：靶点最多、研究最热 HDAC IIa 抑制剂 NT160：噁二唑（TFMO）部分作为锌结合部分，具有高选择性，可穿透血脑屏障用于诊断与治疗，目前处于临床前研究。微管蛋白抑制剂化合物 8：噁二唑衍生物结构中引入噻唑和嘧啶，抑制乳腺癌、肺癌和前列腺癌细胞的增殖，优于上市药 Fosbretabulin。 EGFR 抑制剂化合物 12：对 EGFR 酪氨酸激酶的抑制作用，优于临床药物 Erlotinib。 KRAS G12C 抑制剂化合物 37（BI0474）：通过 1,2,4-噁二唑骨架增加分子的构象刚性，减少配体-受体结合的熵损失。作为共价可逆抑制，体内抑瘤率 98%，目前处于临床前研究。左右滑动查看更多 SIRT2 选择性抑制剂化合物 41-43 系列：利用高通量筛选发现的苗头化合物与靶点进行分子对接，发现一系列单 μM 级抑制剂，选择性高于 SIRT1/3/5，诱导白血病细胞凋亡。 GSK3β/CDK1 抑制剂化合物 44b、45b：源于海洋生物碱 Topsentin，抗胰腺癌活性优异。抗菌、抗真菌、抗分枝杆菌活性抗菌 DNA 旋转酶抑制剂：化合物 55 作为 1,2,4-噁二唑与吡咯烷的杂合物，对大肠杆菌 DNA 旋转酶的 IC50=0.012 μM，优于临床药物新生霉素。抗 MRSA：化合物 60 作为含 1,2,4-噁二唑的叔芳香酰胺衍生物，靶向心磷脂，破坏膜完整性，低耐药、低溶血。窄谱抗艰难梭菌：化合物 57、59，不破坏肠道菌群；抗生物膜：化合物 64a 对多种细菌的 MIC=3.12 μg/ml，优于临床药物环丙沙星。抗真菌化合物 69b：含吡唑结构的 1,2,4-噁二唑衍生物，对稻瘟病菌的 EC50=5.49 μg/ml，优于临床杀菌剂联苯吡菌胺；靶点：琥珀酸脱氢酶 SDH，对植物致病真菌高效。抗结核化合物 73a：含吲哚结构的 5-氧代-1,2,4-噁二唑衍生物，对结核分枝杆菌 H37Rv 的 MIC=0.78 μg/ml，优于临床药物乙胺丁醇。靶点：InhA、Pks13，细胞选择性高抗寄生虫与杀虫活性抗疟原虫：阿斯特米唑的 1,2,4-噁二唑衍生物，对恶性疟原虫抑制疗效好，优于阿斯特米唑，具有良好的代谢稳定性、低 hERG 心脏毒性；抗病毒活性抗肠病毒 D68、柯萨奇病毒化合物 89：IC50=58 nM，靶向 VP1 衣壳蛋白，体内降病毒载量。抗新冠病毒（SARS-CoV-2）化合物 97：1,2,4-噁二唑作为生物电子等排体替换原有的酰胺键，以提高抑制剂的代谢稳定性，PLpro IC50=1.0 μM，EC50=4.3 μM，成药性好。抗乙肝病毒（HBV）化合物 93：苯并咪唑取代的 1,2,4-噁二唑衍生物，对野生 / 耐药株均有效，同时激活 TLR8。抗炎活性化合物 101：含哌嗪结构的 3,5-二取代 1,2,4-噁二唑衍生物，在蛋白质变性抑制试验中展现出与临床药物双氯芬酸钠相当的抗炎活性，活性优于 Diclofenac。通路：NF-κB、MAPK、Nrf2-ARE、sEH、IL-17A/STAT3。神经保护与中枢疾病抗 AD 化合物 106：多靶点抗阿尔茨海默病药物，可同时抑制乙酰胆碱酯酶（AChE）和激活 Nrf2 通路，优于临床药物多奈哌齐。化合物 108：优于 Donepezil，可跨血脑屏障。抗亨廷顿化合物 109：首个选择性 HDAC4 蛋白降解剂，通过泛素-蛋白酶体系统降解 HDAC4，在亨廷顿病小鼠模型的皮质神经元中展现出良好的活性。抗多发性硬化 BTK 抑制剂：化合物 110、111，高选择性，其中化合物 111 具有更高的选择性，已进入自身免疫性疾病的临床试验。其他重要活性抗动脉粥样硬化：化合物 113a：酸性鞘磷脂酶（ASM）抑制剂，可降低 IL-6、TNF-α 和 MCP-1 等炎症因子的水平，减少主动脉脂质斑块的形成；化合物 114：通过激活 Nrf2/HO-1 通路抑制氧化低密度脂蛋白诱导的血管内皮细胞凋亡，减少 ICAM-1 和 VCAM-1 的表达。抗糖尿病与代谢性疾病：化合物 117：GPR119 激动剂，具有良好的药代动力学性质，可显著降低啮齿类动物的血糖水平；化合物 118（V-0219）：GLP1R 别构激动剂，可增强胰岛素分泌，减少食物摄入，改善葡萄糖耐量；化合物 119（BMS-986339）：法尼醇 X 受体（FXR）激动剂，具有组织选择性激活特性，在非酒精性脂肪性肝炎（NASH）模型中展现出良好的抗纤维化活性。镇痛药物化合物 120（GDC-6599）：TRPA1 拮抗剂，是首个进入 II 期临床试验的 TRPA1 拮抗剂，用于呼吸系统疾病的治疗。抗纤维化药物化合物 122：S1PR1 选择性激动剂，口服生物利用度高，在小鼠溃疡性结肠炎模型中展现出显著的治疗效果。 ADME 与药代动力学性质 1,2,4-噁二唑骨架整体展现出良好的 ADME（吸收、分布、代谢、排泄）和药代动力学性质：多数符合Lipinski 五规则；代谢稳定性高（核心优势）；口服吸收好、生物利用度高；部分可穿透血脑屏障；靶点选择性高、正常细胞毒性低；少数化合物存在潜在遗传毒性，可通过结构优化规避。 ▼ 推荐相关阅读 ▼ 氨基氧杂环丁烷 | 作为酰胺与磺酰胺的双重等排体潜力被解锁 2026-02-09 综述｜杂螺环全解析：从合成路线到哌嗪/吗啉生物等排体的药物潜力 2026-01-27 总结｜一文搞定苯环等排体（如BCP、BCHex、BCHep、BCO），新型分子砌块的设计 2025-10-21 吡啶/哌啶生物等排体 | 2-氮杂双环[2.2.2]辛烷及1,2-BCP的工业化突破 2025-09-28 生物等排体系列｜开源BioSTAR工作流：生物等排体的数据评估模型 2025-08-07 「等排体专栏」｜间苯的水溶性电子等排体 2025-01-24 生物等排体｜双环[1.1.0]丁烷（BCB）合成综述 2024-12-20 生物等排体｜三氮唑衍生物的合成进展｜综述 2024-11-11 生物等排体专栏｜四氮唑：药物设计中的多能之星 2024-10-05 为什么双环[m.n.k]烷烃能成为芳环的电子等排体？ 2024-01-05

2026-04-24

·全息象数生态工程

植物次生代谢物的生物活性作用与人体临床应用效果研究报告

植物次生代谢物的生物活性作用与人体临床应用效果研究报告摘要植物次生代谢物是植物在长期进化过程中，为适应环境胁迫、抵御生物侵害、实现种间通讯而合成的非初级生命必需有机化合物，核心分为萜类、生物碱、酚类三大类。这类物质既是植物应对外界环境的“化学防御武器”，也是现代药物研发、功能食品创制的核心宝库，更是中医药“药食同源”理论的物质基础。本报告系统梳理了三大类次生代谢物的化学特征、核心生物活性与分子作用机制，对比分析了动物实验的药效潜力与人体临床转化的现实差异，拆解了青蒿素、紫杉醇、吗啡等经典药物的完整转化路径，总结了临床转化的共性瓶颈，并结合2024-2025年前沿研究进展提出了破局策略。本报告旨在为天然产物新药研发、道地药材品质提升、中医药现代化与精准健康管理提供系统性的科学依据。一、引言植物次生代谢物的合成与积累，本质是植物对环境胁迫的适应性响应——纬度、海拔、季节、昼夜等外界环境信号（外S值）通过细胞转录调控网络，定向驱动次生代谢物的合成，使其成为承载环境信息的“分子信使” 。经过数十亿年的进化，植物次生代谢物已形成结构超20万种的庞大化合物库，其广谱的药理活性已成为现代医学发展的重要源泉：全球临床应用的小分子药物中，超60%直接或间接来源于天然次生代谢物，其中抗疟、抗肿瘤、抗感染领域的重磅药物，核心骨架均来自植物次生代谢物。与此同时，次生代谢物的临床转化呈现显著的两极分化：萜类、生物碱类已诞生青蒿素、紫杉醇、吗啡等改变临床实践的重磅药物，而酚类（黄酮类）虽在动物实验中展现出优异的抗氧化、抗炎、抗肿瘤活性，却始终面临“动物实验数据华丽，人体临床效果微弱”的转化鸿沟。本报告将从分子机制、转化路径、瓶颈挑战与前沿突破四个维度，系统阐述植物次生代谢物的生物活性与临床应用现状。二、植物次生代谢物的分类与天然生物学特性根据化学结构与生物合成途径，植物次生代谢物可分为三大核心类别，其天然功能均围绕植物的环境适应与防御展开，也是其人体药理活性的生物学基础。类别：核心结构特征，主要亚类，天然生态功能—— 萜类：以异戊二烯单元为基本结构，通过甲羟戊酸途径合成；单萜、倍半萜、二萜、三萜、四萜（类胡萝卜素）：抵御植食性动物与病原微生物、调节生长发育、吸引传粉者、应对非生物胁迫（低温、干旱、紫外线）。生物碱：含氮碱性有机化合物，多具有杂环结构，主要由氨基酸衍生合成：异喹啉类、吲哚类、喹啉类、嘌呤类；强效防御植食性动物与病原菌，是植物最核心的“化学毒素武器”，部分参与植物氮代谢调节。酚类：苯环上连接一个或多个羟基，通过莽草酸途径合成；黄酮类、酚酸类、单宁类、木脂素类、芪类；抗氧化、抵御紫外线损伤、抑制病原菌生长、调节种间竞争、作为细胞壁结构成分三、三大类次生代谢物的核心生物活性与分子作用机制 3.1 萜类化合物：成药性最高的天然产物宝库萜类化合物结构多样、靶点清晰，是目前临床转化最成功的次生代谢物类别，其药理活性覆盖抗疟、抗肿瘤、抗炎、免疫调节、神经保护等多个领域，核心作用机制如下： 1. 抗疟与抗感染活性代表物质为倍半萜内酯类的青蒿素，其核心机制是通过铁介导的活化产生大量自由基，特异性破坏疟原虫的膜蛋白与核酸结构，快速清除疟原虫；其衍生物蒿甲醚、青蒿琥酯还对血吸虫、弓形虫等寄生虫具有显著抑制活性，是全球抗疟治疗的基石药物。 2. 抗肿瘤活性代表物质包括二萜类的紫杉醇、冬凌草甲素，三萜类的人参皂苷，以及倍半萜类的Combretastatin A-4。其中，紫杉醇通过特异性结合微管蛋白并抑制其解聚，阻断癌细胞有丝分裂，使细胞周期停滞于G2/M期，最终诱导癌细胞凋亡；冬凌草甲素通过抑制VEGF信号通路，阻断肿瘤新生血管生成；Combretastatin A-4作为血管阻断剂，可特异性破坏肿瘤血管血流，实现“饿死肿瘤”的治疗效果。 3. 抗炎与免疫调节活性代表物质包括二萜类的穿心莲内酯、银杏内酯B，以及新型二倍半萜leu-F。穿心莲内酯通过抑制活性氧介导的NF-κB信号通路激活，使NLRP3炎症小体失活，显著下调TNF-α、IL-1β、IL-6等促炎因子的表达；银杏内酯B通过抑制MAPK通路中p38、JNK蛋白的磷酸化，减轻骨关节炎症；中科院昆明植物所发现的leu-F通过共价结合GAPDH的Cys152残基，阻断糖酵解过程并抑制AKT-mTOR信号通路，在银屑病、多发性硬化症动物模型中展现出优于临床一线药物的抗炎活性与安全性。 4. 代谢与神经保护活性三萜类的人参皂苷可通过调节线粒体功能改善能量代谢，抑制神经元凋亡；青蒿素衍生物蒿甲醚通过靶向线粒体蛋白酶LONP1，降解卵巢雄激素合成关键酶CYP11A1，改善多囊卵巢综合征（PCOS）患者的激素紊乱，已进入临床探索阶段。 3.2 生物碱类：强效药理活性与毒性并存的“双刃剑” 生物碱是植物中生物活性最强的次生代谢物，多数具有明确的分子靶点与量效关系，但普遍存在治疗窗窄、毒性风险高的特点，其核心药理活性如下： 1. 中枢镇痛与神经调控活性代表物质为异喹啉类的吗啡，其核心机制是高选择性激动中枢μ型阿片受体，阻断痛觉信号传导，产生强效镇痛作用，是全球重度癌痛管理的金标准。苦参碱、槐定碱等生物碱可通过激活大麻素CB1受体，促进抑制性神经递质GABA的合成与释放，调节中枢神经兴奋性，发挥镇静与神经保护作用。 2. 抗肿瘤活性代表物质包括吲哚类的长春新碱、长春碱，喹啉类的喜树碱衍生物，以及三尖杉酯碱类的高三尖杉酯碱。长春新碱通过抑制微管聚合，阻断肿瘤细胞纺锤体形成，使细胞分裂停滞，是儿童急性淋巴细胞白血病（ALL）、淋巴瘤联合化疗的核心药物，可将儿童ALL的5年生存率从不足10%提升至80%以上；喜树碱半合成衍生物伊立替康、拓扑替康通过抑制拓扑异构酶Ⅰ，阻断肿瘤细胞DNA复制与转录，是转移性结直肠癌、复发性卵巢癌的一线治疗药物；高三尖杉酯碱通过抑制肿瘤细胞蛋白合成，对酪氨酸激酶抑制剂耐药的慢性髓系白血病（CML）仍具有显著疗效。 3. 抗感染与抗菌活性喹啉类的奎宁通过干扰疟原虫DNA复制发挥抗疟作用，是最早用于临床的抗疟生物碱；小檗碱（黄连素）通过抑制细菌菌毛黏附、破坏细菌细胞膜完整性，对大肠杆菌、金黄色葡萄球菌等病原菌具有显著抑制作用，是感染性腹泻的临床常用药物。 4. 代谢与神经保护活性小檗碱可通过抑制肠道α-葡萄糖苷酶活性、调节肠道菌群结构，改善2型糖尿病患者的糖脂代谢紊乱；异喹啉类生物碱四氢巴马汀可通过下调L型钙通道表达、激活钙泵蛋白SERCA，维持神经元钙稳态，打断“氧化应激-钙超载-线粒体功能障碍”的神经退行恶性循环，在脑缺血、阿尔茨海默病模型中展现出显著的神经保护作用。 3.3 酚类化合物：抗氧化为核心的广谱活性物质酚类化合物是植物中分布最广的次生代谢物，以抗氧化、抗炎活性为核心，兼具心血管保护、代谢调节、化学预防等作用，但其靶点特异性较弱、口服生物利用度极低，临床转化难度显著高于前两类。 1. 抗氧化与心血管保护活性代表物质包括茶多酚（EGCG）、白藜芦醇、槲皮素、橙皮苷等。这类物质可通过酚羟基直接清除自由基、淬灭单线态氧，上调Nrf2/HO-1抗氧化通路，减轻血管内皮氧化应激损伤；同时可抑制血管平滑肌细胞增殖、改善血管舒张功能，延缓动脉粥样硬化进程。流行病学研究证实，长期膳食摄入黄酮类化合物可显著降低心血管疾病发病风险，但短期补充剂的临床效果微弱。 2. 抗炎与肠道黏膜保护活性黄酮类的异牡荆苷、槲皮素可通过抑制NF-κB/MAPK炎症通路，下调促炎因子表达，改善溃疡性结肠炎模型小鼠的肠道黏膜损伤；京尼平苷可通过上调肠道紧密连接蛋白表达，修复肠黏膜屏障，在结肠炎治疗中展现出良好潜力。 3. 代谢调节活性儿茶素、芹菜素可通过抑制α-葡萄糖苷酶活性，延缓肠道碳水化合物吸收，其体外降糖活性优于临床一线药物阿卡波糖；槲皮素、芦丁可通过上调骨骼肌GLUT4表达，改善胰岛素抵抗，在糖尿病动物模型中可显著降低空腹血糖与糖化血红蛋白水平。 4. 抗肿瘤化学预防活性 EGCG、白藜芦醇可通过抑制肿瘤细胞增殖、诱导凋亡、阻断肿瘤血管生成，在多种癌细胞模型中展现出显著活性；但在人体临床中，仅可作为前列腺癌前病变等肿瘤高危人群的化学预防剂，无法作为肿瘤治疗的主力药物。四、动物实验药效证据与人体临床转化对比分析 4.1 萜类：从实验室到临床的转化标杆萜类化合物是天然产物临床转化最成功的类别，诞生了多个改变临床实践的经典药物，其完整转化路径可总结为“活性发现-机制阐明-瓶颈突破-临床验证”的闭环模式。经典案例1：青蒿素——从古籍验方到全球抗疟基石 - 活性发现：1969年屠呦呦受《肘后备急方》启发，突破高温水煎的传统提取方式，采用低温乙醚提取法获得青蒿中性提取物，对鼠疟的抑制率达100%； - 临床验证：科研人员以身试药确认安全性后，在海南疫区完成首批21例临床验证，证实其抗疟活性； - 瓶颈突破：初代青蒿素片剂水溶性差、口服生物利用度低，单用复发率高达50%；通过结构修饰研发出油溶性的蒿甲醚（活性提升6倍）与水溶性的青蒿琥酯（可静脉注射抢救重症脑疟），最终形成青蒿素联合疗法（ACTs），治愈率提升至97%； - 临床地位：WHO推荐的全球抗疟一线方案，据估计已挽救全球数百万人生命；目前其适应症已拓展至代谢相关脂肪性肝炎（MASH）、系统性红斑狼疮（SLE）、多囊卵巢综合征（PCOS），多个适应症已进入II期临床。经典案例2：紫杉醇——从环保危机到抗癌基石 - 活性发现：1960-1979年从太平洋紫杉树皮中分离得到，其独特机制为促进微管蛋白聚合、阻断癌细胞有丝分裂，靶点不可替代； - 瓶颈突破：初期需砍伐6万棵红豆杉树皮才能生产1kg药物，引发严重环保危机；法国科学家Potier利用欧洲红豆杉针叶中的10-DAB完成半合成，解决了工业化生产难题；原研制剂采用蓖麻油助溶，易引发严重过敏，后续开发的白蛋白结合型、脂质体紫杉醇无需抗过敏预处理，且对胰腺癌、三阴性乳腺癌展现出更优疗效； - 临床地位：卵巢癌、乳腺癌、非小细胞肺癌的标准化疗基石，在HER2+乳腺癌中联合靶向药可将患者中位生存期从17.9个月延长至24.8个月；2025年全球首个口服紫杉醇软胶囊进入临床试验，有望实现从医院输注到居家口服的治疗模式革新。此外，长春花生物碱、喜树碱衍生物、鬼臼毒素衍生物、高三尖杉酯碱等萜类/生物碱类化合物，均已完成从植物粗提物到临床一线药物的完整转化，成为肿瘤、感染等疾病治疗的核心药物。 4.2 生物碱：疗效与毒性的平衡难题生物碱类化合物的临床转化呈现显著分化：吗啡、长春新碱、小檗碱等已成为临床不可或缺的药物，而马钱子碱、雷公藤碱等虽在动物实验中展现出优异的抗肿瘤、抗炎活性，却因神经毒性、心脏毒性、治疗窗窄等问题，临床推进缓慢。 - 成功转化核心要素：明确的作用靶点、可控的毒性风险、清晰的量效关系，以及通过剂型改良、结构修饰降低毒性的技术路径； - 转化失败核心原因：治疗窗过窄，有效剂量与中毒剂量高度重叠，且缺乏有效的减毒手段，难以满足临床用药的安全性要求。 4.3 酚类：难以跨越的临床转化鸿沟酚类化合物在动物实验中展现出全面的药理活性，但在人体临床中始终难以复现动物实验的优异效果，形成了显著的“转化鸿沟”，核心对比如下：应用场景动物实验（理想化结果）人体临床（现实效果）心血管保护显著降低血压、逆转动脉粥样硬化斑块、减少心血管事件流行病学提示长期膳食摄入有益，短期补充剂效果微弱，无明确的临床终点获益代谢调节槲皮素显著改善胰岛素抵抗、降低空腹血糖40%以上对空腹血糖的改善效果不一致，个体差异极大，无统一的临床推荐剂量抗肿瘤 EGCG、白藜芦醇显著抑制多种癌细胞增殖、诱导凋亡、抑制转移仅可作为肿瘤高危人群的化学预防剂，无法作为肿瘤治疗药物，高剂量补充存在肝肾毒性风险抗炎多种黄酮类化合物显著降低动物模型炎症因子水平、改善炎症损伤对慢性炎症性疾病的临床改善效果有限，仅可作为辅助干预手段转化鸿沟的核心成因包括：① 口服生物利用度极低，多数黄酮类化合物口服生物利用度不足5%，肠道内快速被代谢为无活性产物，人体血药浓度远低于动物实验的有效剂量；② 动物实验多采用超高剂量，而人体长期超1000mg/天摄入存在明确的肝肾毒性风险；③ 种属差异显著，啮齿类动物与人类的药物代谢酶、靶点分布存在本质差异，实验结果难以直接外推。五、次生代谢物临床转化的共性瓶颈与挑战 5.1 药代动力学核心缺陷这是次生代谢物临床转化的首要瓶颈，主要表现为：水溶性差（如紫杉醇、喜树碱）、口服生物利用度低（如多酚类、多数萜类）、体内半衰期短（如青蒿素单用半衰期不足2小时）、首过效应强，导致药物难以在人体内达到有效治疗浓度，无法复现动物实验的药效。 5.2 安全性与治疗窗难题生物碱类化合物普遍存在治疗窗窄的问题，有效剂量与中毒剂量高度重叠，易引发呼吸抑制、神经毒性、心脏毒性等严重不良反应；吗啡类生物碱还存在成瘾性与耐受性风险，需严格管制。而酚类化合物虽整体安全性良好，但长期高剂量摄入仍存在肝损伤、胃肠道紊乱等风险，且缺乏长期安全性的临床数据。 5.3 质量标准化与质控难题次生代谢物在植物中的含量受产地、纬度、海拔、季节、采收时间、加工方式等多种因素影响，道地产区与非道地产区的药材，其核心活性成分含量可相差数倍至数十倍，导致产品质量不均一，给临床剂量控制、疗效稳定性与一致性评价带来极大挑战。目前我国已出台《植物激素类次生代谢产物的生物活性测定》系列国家标准，以及《中药标准管理专门规定》，但针对药用活性次生代谢物的成药性评价、质量控制标准仍有待完善。 5.4 种属差异与临床前评价局限性现有临床前评价主要依赖啮齿类动物模型，而啮齿类与人类在药物代谢酶（如CYP450家族）、药物转运体、靶点表达与分布等方面存在显著的种属差异，导致动物实验的药效、毒性结果与人体临床实际存在较大偏差，是临床转化失败的核心原因之一。 5.5 作用机制的特异性与清晰度不足多数酚类化合物的药理活性基于非特异性的抗氧化作用，缺乏明确的高亲和力靶点，多靶点、多通路的作用模式虽使其具备广谱活性，却也导致其作用机制难以清晰阐明，无法满足现代药物研发的成药性评价要求，限制了其临床转化进程。六、突破临床转化瓶颈的前沿技术与最新进展 6.1 剂型革新与纳米递送技术纳米递送技术是解决次生代谢物水溶性差、生物利用度低的核心手段，2024-2025年的最新进展包括： - 纳米晶与脂质体技术：紫杉醇纳米晶可将其溶解度提升400倍，脂质体、白蛋白结合型紫杉醇已实现临床广泛应用，全球首个口服紫杉醇软胶囊通过脂质体纳米递送技术，攻克了紫杉醇口服吸收的世纪难题，已进入中美临床试验； - 植物体复合物技术：将黄酮类化合物与磷脂、橄榄油等制备成植物体复合物，可显著提升其肠道吸收效率，槲皮素、水飞蓟宾植物体复合物的口服生物利用度较原型提升5-10倍，在COVID-19、糖尿病的临床研究中展现出显著获益； - 智能响应型纳米载体：结合肿瘤微环境酸性、高还原型特征的智能纳米囊泡，可实现药物在病灶部位的靶向释放，降低全身毒性，在胰腺癌、三阴性乳腺癌模型中展现出优异的疗效与安全性。 6.2 结构修饰与前药设计通过化学结构修饰与前药设计，可针对性解决次生代谢物的水溶性差、毒性高、代谢不稳定等问题，是天然产物成药的经典路径： - 喜树碱原型药水溶性差、膀胱毒性严重，通过结构修饰开发的伊立替康、拓扑替康，解决了水溶性与毒性问题，成为临床一线抗肿瘤药物； - 青蒿素通过结构修饰得到的蒿甲醚、青蒿琥酯，显著改善了脂溶性/水溶性，延长了半衰期，提升了抗疟活性； - 将NO释放基团与神经保护药效团结合，制备的NO供体型前药，可同时发挥NMDA受体拮抗与改善脑血流的双重作用，为神经退行性疾病治疗提供了新方向。 6.3 合成生物学与绿色生产技术合成生物学技术可通过工程化改造微生物，实现稀缺次生代谢物的异源高效合成，解决天然提取资源稀缺、成本高、环保压力大的问题： - 利用工程化酵母菌实现青蒿酸的高效异源合成，已实现工业化生产，彻底解决了青蒿素的原料供应问题； - 广州中医药大学团队通过代谢工程重构黄酮芸香糖苷生物合成路径，在番茄与烟草中实现了静脉活性成分地奥司明的高效合成，为高价值药用黄酮的绿色生产提供了新方案； - 上海交大团队通过定向进化获得高精度人工法尼醇环氧化酶，实现了复杂萜类化合物的简洁高效全合成，解决了天然提取丰度低的核心瓶颈。 6.4 老药新用与适应症拓展基于已上市天然产物药物的安全性数据，开展老药新用研究，可大幅缩短研发周期、降低研发成本，是近年来次生代谢物临床转化的热点方向： - 青蒿素类药物从抗疟拓展至MASH、SLE、PCOS等免疫与代谢性疾病，多个适应症已进入II期临床，有望成为首个治疗SLE的萜类口服药； - 小檗碱从腹泻治疗拓展至2型糖尿病、血脂异常、多囊卵巢综合征，已获得大量临床证据支持； - 三尖杉酯碱类药物从白血病治疗拓展至骨髓纤维化等血液系统疾病，进一步拓展了临床应用场景。 6.5 联合用药与协同治疗策略次生代谢物与化疗、靶向、免疫治疗药物联用，可发挥增敏、逆转耐药、降低毒副作用的协同效应，是突破临床应用瓶颈的重要方向： - 多酚类化合物作为化疗增敏剂，可通过抑制ABC转运蛋白活性，逆转肿瘤细胞的多药耐药，提升化疗药物的疗效； - 萜类、生物碱类化合物与免疫检查点抑制剂联用，可通过调节肿瘤微环境、激活抗肿瘤免疫应答，提升免疫治疗的响应率； - 多种次生代谢物联用，可通过多靶点协同作用，降低单药剂量与毒性，提升治疗效果，也是中药复方配伍的现代化科学内涵。 6.6 精准成药性评价体系构建针对传统动物模型的种属差异局限，类器官芯片、人源化动物模型、多组学技术等新型评价体系，可更精准地模拟次生代谢物在人体内的吸收、分布、代谢、排泄过程，提升临床前评价的准确性，降低临床转化失败风险。其中，肠道-肝脏双器官联动芯片，可实现次生代谢物肠道吸收与肝脏代谢的同步模拟，已成为天然产物成药性评价的前沿工具。七、总结与临床应用提示 7.1 核心总结植物次生代谢物作为自然界赋予的“化学宝库”，已为现代医学发展做出了不可替代的贡献，三大类别的成药性与临床应用价值呈现显著差异： 1. 萜类化合物：结构明确、靶点清晰、成药性最高，已诞生青蒿素、紫杉醇等多个改变临床实践的重磅药物，是天然产物新药研发的核心主战场，未来的核心发展方向是老药新用、剂型革新与合成生物学绿色生产； 2. 生物碱类化合物：药理活性强效、靶点明确，但普遍存在治疗窗窄、毒性风险高的问题，临床转化的核心是通过结构修饰、剂型改良平衡疗效与毒性，同时挖掘其在神经、代谢性疾病中的新适应症； 3. 酚类化合物：抗氧化、抗炎活性广谱，膳食安全性良好，但口服生物利用度极低、靶点特异性不足，膳食价值远大于药物价值，临床定位以慢病预防、辅助治疗为主，难以替代化学药物成为治疗主力，未来的核心突破方向是通过递送技术提升生物利用度，明确精准适用人群。整体而言，次生代谢物的临床转化已从“广泛筛选活性成分”的粗放模式，转向“机制驱动、精准递送、标准化质控”的精细化模式，而中医药“药食同源”“道地药材”的传统理论，也将通过次生代谢物的机制研究，实现现代化、科学化的传承与创新。 7.2 临床与消费应用提示 1. 生物碱类药物均为处方药，治疗窗窄、毒性风险高，必须严格遵医嘱使用，严禁自行服用含马钱子、雷公藤等有毒生物碱的植物提取物，避免引发严重不良反应；吗啡等阿片类镇痛药受严格管制，需防范成瘾性与呼吸抑制风险。 2. 切勿因动物实验的“神奇数据”盲目服用高剂量植物提取物，尤其是超高浓度的白藜芦醇、姜黄素、EGCG等多酚类补充剂，长期超剂量摄入可能引发肝损伤、胃肠道紊乱等健康风险，膳食补充需遵循适量原则。 3. 酚类、萜类膳食补充剂仅可作为健康辅助干预手段，不能替代药物治疗，慢性病患者在服用补充剂前需咨询医师，评估与治疗药物的相互作用风险。 4. 优先选择有明确质量标准、活性成分含量清晰的标准化提取物产品，避免购买来源不明、成分不清的植物粗提物，保障使用的安全性与有效性。参考文献 1. 屠呦呦. 青蒿素的发现：传统中医献给世界的礼物[J]. 中国科学: 生命科学, 2016, 46(12): 1297-1306. 2. 中国科学院昆明植物研究所. 基于植物化学防御发现抗银屑病新型天然药物先导分子[R]. 2025. 3. 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2026-04-16

·GlobeNewswire-Health Care

Oncotelic Therapeutics Reports FY 2025 Results Highlighting $249M Net Income and JV Pipeline Progress

AGOURA HILLS, Calif., April 16, 2026 (GLOBE NEWSWIRE) -- Oncotelic Therapeutics, Inc. (OTCQB:OTLC) (“Oncotelic”, the “Company” or “We”), a clinical-stage biopharmaceutical company developing drugs for the treatment of orphan oncology indications, as well as antisense and small molecule injectable drugs for the treatment of cancer, today announced its financial results for the fiscal year ended December 31, 2025 (“FY 2025”), as compared to the fiscal year ended December 31, 2024 (“FY 2024”). The financial results are based on the 2025 Annual Report on Form 10-K (“Form 10-K”) as filed with the Securities and Exchange Commission (“SEC”) on April 15, 2026. The Company recorded net income after tax of approximately $249.0 million, compared to a net loss of approximately $4.8 million in the prior year. The net income was primarily driven by a non-cash increase in the estimated fair value of the Company’s investment in GMP Biotechnology Limited (“GMP Bio”), its joint venture (“JV”), of approximately $365.4 million, as determined by an independent third-party ASC-compliant valuation, partially offset by a deferred income tax provision of approximately $111.6 million. Highlights for FY 2025 and thereafter: 2025 marked a transformational year for Oncotelic, highlighted by the successful completion of its first combination immunotherapy trial, the formalization of Sapu Bio and Sapu Nano, subsidiaries of GMP Bio, in which the Company has 45% equity interests. Additional achievements included dedicated development platforms, expansion of the Company’s AI-enabled research capabilities, and continued advancement of its joint venture programs. Joint Venture Valuation and Investment In November 2025, the Company recorded a non-cash increase in the fair value of its investment in GMP Biotechnology Limited based on an independent third-party valuation, resulting in a gain of approximately $365.4 million and a carrying value of approximately $388.0 million. This increase reflects estimated development progress and market-based assumptions and does not represent product revenue or cash received. A corresponding deferred income tax liability of approximately $111.6 million was recorded. Sapu Bio and Sapu Nano: Dual-Platform Strategy During 2025, GMP Bio formalized its two primary subsidiaries. Sapu Bio concentrates on OT-101 (TGFβ2 antisense) clinical development, regulatory advancement, and biomarker-driven positioning. Sapu Nano serves as the dedicated nanomedicine arm of the JV, advancing the Deciparticle™ platform into clinical-stage assets, partnerships, and commercialization. Together they form a diversified and scalable development platform. Deciparticle™ Nanoparticle Platform The Deciparticle™ platform utilizes ultra-small amphiphilic constructs (below ~20 nanometers) enabling enhanced tumor penetration and distribution. The JV is advancing six candidates: Sapu-001 (paclitaxel), Sapu-003 (everolimus), Sapu-004 (carboplatin), Sapu-005 (palbociclib), and Sapu-006 (docetaxel), in addition to OT-101. Everolimus formulation development is complete with a global clinical trial enrolling in Australia. Palbociclib and docetaxel INDs are expected in 2026. The platform is protected by more than 15 patent families. OT-101 Clinical Program In March 2025, we completed a Phase 1 clinical trial (NCT04862767) evaluating OT-101 in combination with IL-2 in Seoul, South Korea for advanced or metastatic solid tumors. The combination showed a tolerable safety profile with no unexpected safety signals. The JV plans to advance OT-101 plus IL-2 into further studies exploring synergies with checkpoint inhibitors such as PD-1 blockers. Separately, the JV initiated a Phase 2/3 trial for OT-101 in pancreatic cancer and is actively enrolling participants. Over ten patent families have been filed related to TGFβ2 as a prognostic indicator for cancer survival. PDAOAI (“AI”) Platform PDAOAI, the Company’s proprietary AI-enabled knowledge platform, was significantly expanded during 2025 into a core infrastructure layer supporting research, biomarker discovery, and regulatory documentation. By late 2025, PDAOAI evolved into a large-scale knowledge platform built around a TGF-β-centric biomedical corpus of over 100,000 curated abstracts with semantic retrieval and cross-referencing capabilities. PDAOAI contributed to at least seven peer-reviewed publications during 2025 across biomarker discovery, tumor microenvironment analysis, nanoparticle drug delivery, and clinical outcome correlations — spanning ovarian, breast, pancreatic, hepatocellular, and glioblastoma tumor types. Notably, the Company identified a novel biomarker signature (High RICTOR / Low RPTOR) predictive of sensitivity to intravenous everolimus based on analysis of over 9,000 tumor samples. GMP Manufacturing Facility The JV’s GMP manufacturing facility in San Diego continued full-scale operations during 2025 under its Drug Manufacturing License from the State of California. The facility utilizes a streamlined “one-pot” manufacturing process for bulk drug production through to finished product, with capabilities for both nonclinical and Phase 1 clinical trial material production. In early 2025, the Company partnered with Shanghai Medicilon, Inc. to access its rapid IND development platform supporting up to 20 IND projects. Results of Operations Below is a presentation of our financial results comparing FY 2025 to FY 2024 and based on our results published in our Form 10-K filed with the SEC on April 15, 2026. FY 2025 compared to FY 2024 Financial Results Overview ONCOTELIC THERAPEUTICS, INC. AND SUBSIDIARIES CONSOLIDATED STATEMENTS OF OPERATIONS For the Year Ended December 31, 2025 2024 Operating expenses: Research and development $4,357 $- General and administrative 3,182,242 376,013 Goodwill impairment (See note 2 and 3) - 3,200,000 Total operating expenses 3,186,599 3,576,013 Income/(Loss) from operations (3,186,599) (3,576,013)Other income (expense): Change in fair value of investment in GMP Bio 365,346,775 - Interest expense, net (885,488) (857,723)Reimbursement for expenses - related party - 22,937 Change in fair value of derivative on debt 353,572 (280,402)Loss on debt conversion (1,058,976) (88,258)Miscellaneous income 5,631 - Total other income (expense) 363,761,514 (1,203,446)Net income (loss) before income taxes 360,574,915 (4,779,459)Provision for income taxes (111,550,000) - Net income (loss) after income taxes 249,024,915 (4,779,459)Net income (loss) before non-controlling interests 249,024,915 (4,779,459)Net loss attributable to non-controlling interests (254,917) (255,527)Net income (loss) attributable to Oncotelic Therapeutics, Inc. $249,279,832 $(4,523,932) Basic net income (loss) per share attributable to common stock $0.59 $(0.01)Basic weighted average common stock outstanding 421,045,524 404,396,473 Basic and diluted net income (loss) per share attributable to common stock $0.59 $(0.01)Basic and diluted weighted average common stock outstanding 422,234,747 404,396,473 We recorded a higher net income per basic share of $0.59 for the year ended December 31, 2025, as compared to net loss per basic share of $0.01 for the year ended December 31, 2024. The Company had no product revenue for either period. We recorded net income of approximately $249.3 million attributable to Oncotelic Therapeutics, Inc. for the year ended December 31, 2025, compared to a net loss of approximately $4.5 million for the year ended December 31, 2024. The higher net income was primarily due to recording a non-cash increase in the estimated fair value of our investment in GMP Bio of approximately $365.3 million, based on an independent third-party ASC-compliant valuation. This non-cash gain was partially offset by a provision for deferred income taxes of approximately $111.6 million, higher general and administrative expenses of approximately $2.8 million primarily driven by stock-based compensation of approximately $2.4 million incurred for common stock and preferred stock issued in connection with services and approximately $0.2 million to settle litigation related to an ex-employee, higher loss on conversion of debt of approximately $1.0 million, partially offset by a favorable change in the value of derivatives on debt of approximately $0.6 million and lower interest expense of approximately $28 thousand. All operational costs associated with OT-101 and the nanoparticle platform are substantially covered by the JV, significantly reducing our direct financial burden until such time we make a determination to commence development of our own compounds. “The independent third-party valuation of our JV’s pipeline represents a significant milestone for the Company and validates the strategic investments we have made since forming the joint venture in 2022. With the successful completion of our Phase 1 OT-101/IL-2 combination trial, the advancement of six Deciparticle™ nanoparticle candidates into various stages of development, and the continued expansion of our PDAOAI platform which contributed to seven peer-reviewed publications this year, the underlying value drivers are tangible and progressing. We are now focused on the next phase of value realization — advancing the JV toward a potential Hong Kong IPO, pursuing a national exchange uplisting for the Company, and converting our pipeline progress into clinical and commercial milestones,” said Vuong Trieu, CEO of Oncotelic. “The progress made by the Company, through GMP Bio, the joint venture with Dragon, over such a short period of time is very impressive. We expect to continue to see significant progress and shareholder value creation by the Company through our ownership in GMP Bio,” said Amit Shah, CFO of Oncotelic. About Oncotelic Oncotelic (f/k/a Mateon Therapeutics, Inc.), was formed in the State of New York in 1988 as OXiGENE, Inc., was reincorporated in the State of Delaware in 1992, and changed its name to Mateon Therapeutics, Inc. in 2016, and Oncotelic Therapeutics, Inc. in November 2020. Oncotelic conducts business activities through Oncotelic and its wholly-owned subsidiaries, Oncotelic, Inc., a Delaware corporation, PointR Data, Inc. (“PointR”), a Delaware corporation, Pet2DAO, Inc., a Delaware corporation; and EdgePoint AI, Inc. (“Edgepoint”), a Delaware Corporation for which there are non-controlling interests, (Oncotelic, Oncotelic Inc., PointR, Pet2DAO and Edgepoint are collectively called the Company). The Company is currently developing OT-101, in addition to five additional compounds, for various cancers and COVID-19 through its joint venture GMP Bio, with Dragon, Artemisinin for COVID-19 and AI technologies for clinical development and manufacturing. In addition, GMP Bio is developing 5 additional nanoparticle compounds in the JV, which has the potential of significant revenues and value. The Company also acquired apomorphine for Parkinson’s Disease, erectile dysfunction and female sexual dysfunction. In addition, the Company is evaluating the further development of its product candidates OXi4503, as a treatment for acute myeloid leukemia and myelodysplastic syndromes, and CA4P, in combination with a checkpoint inhibitor for the treatment of advanced metastatic melanoma. The Company is also planning to address the animal health industry through Pet2DAO. Our principal corporate office is in the United States at 29397 Agoura Road, Suite 107, Agoura Hills, CA 91301 (telephone: 650-635-7000). Our internet address is www.oncotelic.com. Oncotelic’s Cautionary Note on Forward-Looking Statements Any statements contained in this Press Release that are not statements of historical fact are forward-looking statements. In some cases, you can identify forward-looking statements by terminology such as “may,” “will,” “should,” “expect,” “intend,” “plan,” “anticipate,” “believe,” “estimate,” “predict,” “potential,” “continue,” “assumption” or the negative of these terms or other comparable terminology. Statements concerning: our expectations on the timing, success of the JV’s product approvals, commercialization of the JVs products and results of operations of the JV: our expectations on the timing, success, or valuation our JV’s planned initial public offering; the timing, success or continuing valuation of our equity interest in the JV; our ability to secure future debt or equity financing needed to meet operating costs; the timing, costs and other limitations involved in obtaining regulatory approval for any product candidate; the expected efficacy of our product candidates compared to competitive products; anticipated results of our research and development programs as well as preclinical and clinical trials; expected market size, market acceptance for our product candidates; our ability to enter into future partnerships, joint ventures or other corporate transactions, ability of us being able to obtain additional resources, including debt or equity funding, and the expected benefits to be derived from those transactions; the anticipated impact of regulatory and legislative changes in the United States and foreign countries on our product candidates and operations; anticipated trends in revenues, operating expenses or financial position and results of operations; and our estimates regarding anticipated operating income or losses, future performance, future revenues and projected expense; are all forward-looking statements. Forward-looking statements reflect current views about future events and are based on our currently available financial, economic and competitive data and on current business plans. Forward-looking statements are not guarantees of future performance and our actual results may differ significantly from the results discussed or implied in the forward-looking statements. Factors that might cause such differences include, but are not limited to, the factors included in “Risk Factors,” in our Form 10K and the other registration statements and reports that we file with the SEC. The forward-looking statements contained in this press release are based on our current expectations and beliefs concerning future developments and their potential effects on us. We undertake no obligation to update or revise any forward- looking statements, whether as a result of new information, future events or otherwise, except as may be required under applicable securities laws. You should consider the inherent limitations on, and risks associated with, forward-looking statements and not unduly rely on the accuracy of predictions contained in such forward-looking statements. This press release may also include market data related to our business and industry. These market data may include projections that are based on a number of assumptions. While we believe these assumptions to be reasonable and sound as of the date of this press release, if these assumptions turn out to be incorrect, actual results may materially differ from the projections based on these assumptions. As a result, the markets for our product candidates may not grow at the rates projected by these data, or at all. The failure of these markets to grow at these projected rates may have a material adverse effect on our business, results of operations, financial condition and the market price of our common stock. In addition, the Company expects to remeasure the fair value of its investment in GMP Biotechnology Limited on a quarterly basis in accordance with applicable accounting standards, including Accounting Standards Codification (“ASC”) 820, Fair Value Measurement. Such remeasurements are based on significant estimates and assumptions, including clinical development progress, regulatory milestones, market conditions, and comparable company data. As a result, the value of this investment, and the corresponding impact on the Company’s financial statements, may fluctuate materially from period to period, including based on the success or failure of drug development activities within the joint venture pipeline. These fluctuations are non-cash in nature and may not be indicative of the Company’s underlying operating performance or future cash flows. Investor & Media ContactOncotelic Therapeutics, Inc.Investor Relationsir@oncotelic.com Corporate CommunicationsIBNAustin, Texaswww.InvestorBrandNetwork.com512.354.7000 OfficeEditor@InvestorBrandNetwork.com

临床1期财报

100 项与康普瑞丁磷酸二钠相关的药物交易

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KEGG	Wiki	ATC	Drug Bank
-	康普瑞丁磷酸二钠	-	DB12577

研发状态

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适应症	最高研发状态	国家/地区	公司	日期
卵巢癌	临床3期	美国	Oncotelic Therapeutics, Inc.	2016-06-01
卵巢癌	临床3期	比利时	Oncotelic Therapeutics, Inc.	2016-06-01
卵巢癌	临床3期	德国	Oncotelic Therapeutics, Inc.	2016-06-01
甲状腺未分化癌	临床3期	美国	Oncotelic Therapeutics, Inc.	2007-08-01
甲状腺未分化癌	临床3期	以色列	Oncotelic Therapeutics, Inc.	2007-08-01
甲状腺未分化癌	临床3期	意大利	Oncotelic Therapeutics, Inc.	2007-08-01
甲状腺未分化癌	临床3期	俄罗斯	Oncotelic Therapeutics, Inc.	2007-08-01
甲状腺未分化癌	临床3期	英国	Oncotelic Therapeutics, Inc.	2007-08-01
输卵管癌	临床3期	-	Azanta A/S	-
胃神经内分泌肿瘤	临床2期	美国	Oncotelic Therapeutics, Inc.	2014-12-01

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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


NCT02055690 (PAZOFOS, Pubmed \| Obstet Gynecol Surv \| Gynecol Oncol) 人工标引	临床2期	复发性卵巢癌	21	Pazopanib+Fosbretabulin	齋範繭選選齋鏇糧獵衊(願衊壓膚襯衊餘夢鏇糧) = 齋壓鏇蓋繭鹽製壓衊範鏇窪憲遞膚鬱構簾網遞 (夢積廠鹹壓網鏇衊鬱築, 4.1 ~ NE)	积极	2020-03-01
				Pazopanib	齋範繭選選齋鏇糧獵衊(願衊壓膚襯衊餘夢鏇糧) = 顧遞廠觸網繭鹽構簾醖鏇窪憲遞膚鬱構簾網遞 (夢積廠鹹壓網鏇衊鬱築, 1.0 ~ 8.1)
NCT02279602 (OX4219 \| OX4219s, Corporate Publications) 人工标引	临床2期	神经内分泌肿瘤 \| 胃肠道肿瘤	7	Disodium combretastatin A-4 3-O-Phosphate	憲積網壓糧鑰獵夢醖淵(簾繭鑰繭範網網顧積願) = anemia, abdominal pain, fatigue, hypertension, and ALT and AST increases 鬱鬱膚獵鬱遞廠簾繭憲 (範憲鬱蓋夢醖廠醖餘鏇 ) 更多	积极	2017-01-20
NCT00653939 (FALCON, CTgov)	临床2期	鳞状非小细胞肺癌	63	Carboplatin+Paclitaxel+Bevacizumab (Arm 1: Chemotherapy+Bevacizumab)	衊憲鬱構鏇網選齋網艱(鬱簾鬱餘醖齋鏇膚構積) = 鏇願構蓋鏇齋簾網網壓簾鬱繭鏇淵蓋膚艱觸糧 (獵膚壓構積艱夢積窪襯, 積糧壓獵夢顧鏇觸齋憲 ~ 鹽窪廠壓構鏇簾鬱網餘) 更多	-	2015-02-09
				Carboplatin+Paclitaxel+Bevacizumab+Fosbretabulin (Arm 2: Active Comparator+Fosbretabulin)	衊憲鬱構鏇網選齋網艱(鬱簾鬱餘醖齋鏇膚構積) = 艱衊廠範鹽遞夢襯願糧簾鬱繭鏇淵蓋膚艱觸糧 (獵膚壓構積艱夢積窪襯, 糧鏇壓網膚範窪鏇壓鏇 ~ 醖製鏇獵遞蓋糧鑰繭選) 更多
NCT00507429 (FACT, CTgov)	临床2/3期	甲状腺未分化癌	80	Carboplatin+Paclitaxel+CA4P (Arm 1, Active: CA4P + Carboplatin + Paclitaxel)	簾艱鑰襯夢膚獵窪選夢(積壓獵構簾衊窪顧糧餘) = 鑰夢餘廠積鹹遞夢夢簾糧窪蓋積艱憲築糧餘鹽 (齋網鹽醖製艱願製構窪, 築鹽蓋遞夢顧鑰襯獵觸 ~ 蓋遞壓憲窪襯範願觸衊) 更多	-	2014-06-09
				Carboplatin+Paclitaxel (Arm 2, Comparator: Carboplatin + Paclitaxel)	簾艱鑰襯夢膚獵窪選夢(積壓獵構簾衊窪顧糧餘) = 觸醖鑰繭構齋遞鹽鑰夢糧窪蓋積艱憲築糧餘鹽 (齋網鹽醖製艱願製構窪, 遞艱醖繭糧繭夢襯願獵 ~ 憲廠鹹憲鹹繭願廠夢窪) 更多
NCT01570790 (Pubmed \| BMC Pharmacol Toxicol)	临床1/2期	湿性年龄相关性黄斑变性	8	CA4P at a dose of 27 mg/m2	鹽繭艱窪簾選顧選餘窪(鑰築觸築鹹憲衊廠範觸) = 鹽齋蓋鹹鹽鬱夢糧餘糧夢齋鏇願顧餘襯築鏇廠 (壓夢鹹觸糧齋廠壓壓網 ) 更多	-	2013-01-14
				CA4P at a dose of 36 mg/m2	鹽繭艱窪簾選顧選餘窪(鑰築觸築鹹憲衊廠範觸) = 鏇壓獵構簾醖獵夢廠蓋夢齋鏇願顧餘襯築鏇廠 (壓夢鹹觸糧齋廠壓壓網 ) 更多
NCT00507429 (FACT, ASCO2011)	临床2/3期	甲状腺未分化癌	80	CA4P + Carboplatin + Paclitaxel	遞淵艱鏇淵繭醖憲壓鬱(衊鹹襯願襯範窪艱鬱醖) = 艱製膚艱醖範鹽鏇範積夢觸觸繭繭衊醖壓夢範 (鬱築餘壓衊範網蓋築觸 ) 更多	积极	2011-05-20
				Carboplatin + Paclitaxel	遞淵艱鏇淵繭醖憲壓鬱(衊鹹襯願襯範窪艱鬱醖) = 廠顧網醖網壓積憲鑰艱夢觸觸繭繭衊醖壓夢範 (鬱築餘壓衊範網蓋築觸 ) 更多
NCT00653939 (FALCON, ASCO2011)	临床2期	非小细胞肺癌	63	CA4P + carboplatin + paclitaxel + bevacizumab	繭蓋鹽襯鹹齋餘築憲範(憲鬱獵選淵蓋鑰構遞糧) = more common on the CA4P Arm 襯襯簾齋窪夢憲鏇鹽網 (鹽衊襯製鹽顧簾壓構膚 ) 更多	-	2011-05-20
				carboplatin + paclitaxel + bevacizumab
NCT00653939 (FALCON, ASCO2010)	临床2期	非小细胞肺癌	50	CA4P + C + P + B	遞窪製遞醖簾窪選遞鏇(鬱淵獵憲壓壓淵鑰淵簾) = 積鏇衊壓憲憲積積築糧餘淵築憲鏇築醖糧選鹽 (夢餘蓋齋廠製廠夢鏇築 ) 更多	积极	2010-05-20
				C + P + B	遞窪製遞醖簾窪選遞鏇(鬱淵獵憲壓壓淵鑰淵簾) = 醖衊憲淵醖艱糧簾醖衊餘淵築憲鏇築醖糧選鹽 (夢餘蓋齋廠製廠夢鏇築 ) 更多
NCT00060242 (Pubmed \| Thyroid)	临床2期	甲状腺未分化癌	26	Fosbretabulin 45 mg/m(2)	鹽憲鬱鹽衊選艱選範鬱(糧遞願夢選觸選窪夢糧) = 製鏇襯積範範淵淵壓鹽鏇窪膚壓觸獵襯壓範範 (糧願艱膚構憲積廠顧願 ) 更多	-	2009-03-01
ASCO2008 人工标引	临床1期	晚期恶性实体瘤	-	Combretastatin A4 phosphate (CA4P) 45mg/m2	願醖願襯願網襯憲夢網(襯繭積襯積網膚憲齋網) = 壓鏇獵壓選遞夢齋糧範簾衊構網衊艱網壓淵夢 (鹹顧選糧衊憲簾襯觸廠 )	积极	2008-05-20
				Combretastatin A4 phosphate (CA4P) 54mg/m2	願醖願襯願網襯憲夢網(襯繭積襯積網膚憲齋網) = 簾夢齋齋觸繭觸鹹願醖簾衊構網衊艱網壓淵夢 (鹹顧選糧衊憲簾襯觸廠 )