ICVB-1042

1、Apolin Bio Ltd.与上海维亚旦诚创业孵化器管理有限公司（Shanghai Viva Dancheng Entrepreneurship Incubator Management Ltd.）共同公开了一系列多环化合物，这些化合物可作为载脂蛋白A（ApoA；即LPA）/载脂蛋白B-100（APOB）相互作用抑制剂，具有潜在的心血管疾病治疗用途。其中化合物101在ELISA检测中，能够抑制人肝Hep G2癌细胞培养体系中LPA与人APOB的结合，其半数抑制浓度（IC₅₀）为0.69 nM。在人类化Lp(a)转基因小鼠模型中，以10 mg/kg剂量每日口服一次，连续给药3天后，该化合物可使血清LPA水平降低94%（专利号：WO2026130543）。 2、U&S Bio Co. Ltd.公开了一类H⁺/K⁺-ATP酶抑制剂，这些化合物具有改善的稳定性，据称可用于治疗胃肠道疾病、癌症、幽门螺杆菌感染、流涎症、哮喘和气道阻塞等多种疾病。其中实施例5对H⁺/K⁺-ATP酶活性的半数抑制浓度（IC₅₀）<50 nM（专利号：WO2026135359）。 3、Rybodyn Inc.已获得DOW提供的130万美元资助，用于推进两种新型抗体疗法的临床前开发，适应症为肺癌。该资助将支持公司的抗体药物偶联物（ADC）和T细胞衔接器（T-cell engager）项目，这两个项目针对的是两个此前未被发现的细胞表面蛋白，这些蛋白是通过Rybodyn自有的整合型暗转录组与蛋白质组图谱平台——Cypheratlas，直接从患者肿瘤组织中鉴定出来的。借助公司专有的RNA测序及AI驱动发现平台Rybocypher，这些被优先选中的靶点被确认为肺癌中最为普遍存在的细胞表面靶点中的两个。根据DOW资助协议，Rybodyn将针对这两个靶点生成候选治疗药物，表征其生物学活性，并通过体内概念验证研究推进项目进展。此次资助紧随Rybodyn近期完成的种子轮融资（Rybodyn公司新闻稿）。 4、创伤性脑损伤（TBI）影响全球约5000万至6000万人，其中美国是TBI负担最重的国家之一——超过50%的轻度TBI患者在伤后6个月内无法完全康复。TBI可导致严重的脑损伤和长期神经系统并发症。南佛罗里达大学的研究人员聚焦于TBI的脱髓鞘这一病理标志，并测试了一种肝脏X受体（LXR）激动剂GW-396用于TBI的潜在治疗。已知激活LXR可支持少突胶质细胞（OL）成熟、增加髓鞘基因表达并促进髓鞘再生。研究团队在多种体内实验中，使用闭合性颅脑损伤（CHI）诱导的TBI小鼠模型对GW-3965进行了测试。实验观察到，CHI导致皮层区域出现轴突损伤，与假手术组相比，损伤小鼠的mNSS评分（2-6分）升高，提示存在轻度神经功能缺损。此外，TBI小鼠在伤后第1天至第7天体重下降，这与TBI相关代谢应激导致的饮食饮水抑制有关，随后逐渐恢复至与假手术组相当的水平。研究还显示，TBI诱导后，少突胶质前体细胞标志物神经胶质抗原2（NG2）显著减少，但GW-3965治疗可使其恢复。同时，GW-3965还恢复了成熟少突胶质细胞标志物CC1的表达，表明GW-3965（即LXR激活）在TBI后对成熟少突胶质细胞具有保护作用。值得注意的是，TBI后髓鞘蛋白脂蛋白（PLP）和髓鞘碱性蛋白（MBP）均显著降低，但GW-3965治疗可使PLP和MBP均得以恢复，提示GW-3965治疗能够诱导髓鞘再生并在TBI后维持髓鞘完整性。GW-3965还可维持TBI后的轴突完整性，这体现在免疫荧光检测中神经丝重链荧光强度的增加，以及神经元存活和树突细胞结构的改善。对TBI小鼠的行为学测试表明，与未治疗的同胞小鼠相比，GW-3965治疗组在所有测试中的表现均有改善，包括旷场实验（运动能力）、新物体识别实验（长期记忆）和Y迷宫实验（短期记忆）。上述结果表明，在TBI临床前模型中，GW-3965和LXR激活可发挥神经保护作用（参考文献：Zhou, Y. 等，Br J Pharmacol 2026, July 2. doi:10.1111/bph.70575）。 5、Niagen BioscienceInc.（耐健生物科学公司）宣布启动一项针对加速衰老和罕见遗传疾病的研发计划，其子公司 NAD Pharmaceuticals Corp.正在开发该计划下的首个候选药物 NB-4168。该计划将主要聚焦于 NAD⁺（一种对能量代谢、DNA 修复、线粒体功能和细胞应激反应至关重要的辅酶）如何在以 DNA 修复错误和线粒体功能障碍为根本病因的罕见疾病中发挥调节作用。NB-4168 作为 NAD⁺ 前体烟酰胺核糖（NR）的衍生物，目前正以共济失调毛细血管扩张症为首选适应症进行推进。与氯化 NR 相比，NB-4168 被设计为具有显著提高的生物利用度以及差异化的安全性和药代动力学特征。口服给药后，NB-4168 旨在安全地将显著更高剂量的 NR 递送至血液中。NR 可直接进入细胞，并在细胞内通过烟酰胺核糖激酶途径转化为 NAD⁺。在非临床药代动力学研究中，与氯化 NR 相比，NB-4168 已证明其活性部分在血液中的暴露量显著更高，这为其作为一种更具生物利用度的药物候选物进行开发提供了支持。该计划基于已发表的关于 NR 在共济失调毛细血管扩张症中的研究成果，其中两项独立的开放标签临床研究以及多项氯化 NR 的临床前研究报告了神经系统指标和相关生物标志物的改善（信息来源：Niagen Bioscience 新闻稿）。 6、Nuvalent Inc.公开了一类RAC-α丝氨酸/苏氨酸蛋白激酶（AKT1；PKBα）E17K突变体抑制剂，据称可用于癌症治疗。其中实施例9在Alphalisa检测中，能够抑制表达AKT1（E17K突变型）的人前列腺LAPCA4癌细胞中AKT1 Ser473位点的磷酸化，其半数抑制浓度（IC₅₀）<100 nM；而对表达野生型AKT1的人乳腺ZR-75-1癌细胞中AKT1 Ser473磷酸化的抑制活性较低（IC₅₀=100-500 nM）。在CellTiter-Glo检测中，该化合物对表达AKT1（E17K突变型）的LAPCA4癌细胞显示出抗增殖活性（IC₅₀<20 nM；选择性为15-50倍），而对表达野生型AKT1的ZR-75-1癌细胞的选择性更高（IC₅₀≥50 nM）。此外，在人结肠Caco-2癌细胞中，该化合物在10 mM浓度下表现出表观渗透性（专利号：WO 2026136792）。 7、Urogen Pharma Ltd.已获得美国食品药品监督管理局（FDA）对其下一代在研溶瘤病毒UGN-501的IND（新药临床试验申请）批准。一项评估UGN-501经膀胱内给药治疗非肌层浸润性膀胱癌（NMIBC）患者的I期研究预计将于第四季度启动。UGN-501被设计为能够在肿瘤细胞内选择性复制，从而实现直接杀伤肿瘤细胞并诱导抗肿瘤免疫应答。非临床数据显示，该药物在涵盖多种分期和分级膀胱癌细胞系的一系列细胞中均表现出细胞毒活性。UGN-501的基础特性可能具有更广泛的实体瘤适应症应用潜力，公司计划根据后续产生的数据评估这些机会（信息来源：Urogen Pharma新闻稿）。

UroGen Pharma (Nasdaq: URGN) announced on July 8, 2026 that the US FDA cleared its Investigational New Drug application for UGN-501, an oncolytic virus designed for intravesical delivery in patients with non-muscle invasive bladder cancer (NMIBC). The UGN-501 FDA clearance enables the company to initiate a Phase 1 clinical trial, with patient enrollment expected to begin in Q4 2026. NMIBC is among the most prevalent urological malignancies, and its management is complicated by high recurrence rates even after standard treatment. The disease spans a spectrum of risk — from low-grade papillary tumors to carcinoma in situ (CIS) — and despite an expanding roster of approved therapies, a meaningful proportion of patients continue to experience recurrence or progression. Cystectomy, the definitive surgical option, carries substantial morbidity, and bladder-sparing alternatives remain an active area of development. The approved landscape has expanded considerably in recent years. Merck’s BCG live (Tice BCG) remains the first-line standard of care for intermediate- and high-risk disease following transurethral resection of bladder tumor. For patients whose disease does not respond to BCG, options now include Merck & Co.’s pembrolizumab (Keytruda) administered intravenously, Ferring Pharmaceuticals’ nadofaragene firadenovec-vncg (Adstiladrin) — a non-replicating adenoviral gene therapy delivering interferon-alpha 2b — ImmunityBio’s nogapendekin alfa inbakicept-pmln (Anktiva) combined with BCG, and most recently Janssen Biotech’s gemcitabine intravesical system (Inlexzo), approved in September 2025. UroGen itself received approval in June 2025 for mitomycin intravesical solution (Zusduri), a sustained-release hydrogel formulation targeting recurrent low-grade intermediate-risk NMIBC. Against this backdrop, UGN-501 represents UroGen’s push into a mechanistically distinct space: replication-competent oncolytic virus therapy for bladder cancer, a modality not yet represented among approved NMIBC treatments. UGN-501 (ICVB-1042) is an engineered oncolytic adenovirus that exploits aberrant E2F transcription factor activity — a hallmark of tumor cells — to drive selective viral replication within cancer cells. Normal urothelial tissue, which maintains regulated E2F activity, is designed to be spared. Viral replication within tumor cells leads to direct cell lysis, and the resulting immunogenic cell death is intended to trigger a secondary anti-tumor immune response. This dual mechanism — direct cytotoxicity combined with local immune activation — is the defining rationale for the program. Nonclinical data cited by UroGen demonstrated cytotoxic activity across a broad panel of bladder cancer cell lines representing multiple disease stages and grades, though the company has not publicly disclosed the specific parameters or comparative benchmarks from those studies. The planned Phase 1 clinical trial will assess the safety, tolerability, and feasibility of intravesical UGN-501 administration in NMIBC patients, with no public listing available for the study at present. The oncolytic virus field in bladder cancer has no currently approved representative, making UGN-501 an early mover in this specific modality for NMIBC. Within NMIBC specifically, the closest mechanistic neighbor is nadofaragene firadenovec, which uses a non-replicating adenoviral vector to deliver a therapeutic gene locally. UGN-501 is designed to actively replicate within tumor cells, amplifying its cytotoxic effect in situ, whereas nadofaragene firadenovec functions as a one-time gene delivery vehicle without viral replication. Complete response rates in the BCG-unresponsive CIS setting for currently approved agents range from roughly 40% to 62% at six months, with durability remaining a challenge across the class. An oncolytic approach that generates durable local immune memory, if validated clinically, could offer a meaningful complement or alternative to existing options. UGN-501 is UroGen’s third clinical-stage asset and its first in the oncolytic virus modality. The company’s two approved products — Zusduri and its upper tract urothelial cancer therapy — both rely on the proprietary RTGel reverse-thermal hydrogel platform for sustained local drug delivery. UGN-501 does not use RTGel; it represents a distinct biological approach within the same disease focus. This article was generated with AI assistance and reviewed and edited by the AllSci editorial team Explore more at AllSci News: https://allsci.com/news/ Your email address will not be published. Required fields are marked * Comment * Name * Email * Website Privacy Terms About Us Copyright © 2026. AllSci Corp. All rights reserved.