A bioequivalence study of Dasatinib will be carried out in 46 healthy subjects, in fed condition, following the complete replicated design, randomized, comparative of 2 sequences, 2 study formulations, in a single dose of 100 mg of Dasatinib tablets / coated tablets, 4 periods. , with a washout time of 7 days between each dose

开始日期2025-09-01

申办/合作机构-

NCT06124157

/ Not yet recruiting临床3期IIT

A Randomized International Phase 3 Trial of Imatinib and Chemotherapy With or Without Blinatumomab in Patients With Newly-Diagnosed Philadelphia Chromosome-Positive or Philadelphia Chromosome-Like ABL-Class B-Cell Acute Lymphoblastic Leukemia

This phase III trial compares the effect of the combination of blinatumomab with dasatinib and standard chemotherapy versus dasatinib and standard chemotherapy for treating patients with Philadelphia chromosome positive (PH+) or Philadelphia chromosome-like (Ph-Like) ABL-class B-Cell acute lymphoblastic leukemia (B-ALL). Blinatumomab is a bispecific antibody that binds to two different proteins-one on the surface of cancer cells and one on the surface of cells in the immune system. An antibody is a protein made by the immune system to help fight infections and other harmful processes/cells/molecules. Blinatumomab may bind to the cancer cell and a T cell (which plays a key role in the immune system's fighting response) at the same time. Blinatumomab may strengthen the immune system's ability to fight cancer cells by activating the body's own immune cells to destroy the tumor. Dasatinib is in a class of medications called tyrosine kinase inhibitors. It works by blocking the action of an abnormal protein that signals cancer cells to multiply, which may help keep cancer cells from growing. Giving blinatumomab and dasatinib in combination with standard chemotherapy may work better in treating patients with PH+ or Ph-Like ABL-class B-ALL compared to dasatinib and chemotherapy alone.

开始日期2025-05-29

申办/合作机构

National Cancer Institute

NCT06940297

/ Not yet recruiting临床2期IIT

DART: Phase II Study of Dasatinib and Quercetin in Patients With Relapsed, Refractory Multiple Myeloma Receiving CAR-T Therapy

This phase II trial tests how well giving dasatinib and quercetin with cyclophosphamide, fludarabine and chimeric antigen receptor (CAR)-T cell therapy works in treating patients with multiple myeloma that has come back after a period of improvement (relapsed) or that has not responded to previous treatment (refractory). Dasatinib is in a class of medications called tyrosine kinase inhibitors. It works by blocking the action of an abnormal protein that signals cancer cells to multiply, which may help keep cancer cells from growing. Quercetin is a compound found in plants that may prevent multiple myeloma from forming. Chemotherapy such as cyclophosphamide and fludarabine are given to help kill any remaining cancer cells in the body and to prepare the bone marrow for CAR-T therapy. Chimeric antigen receptor T-cell Therapy is a type of treatment in which a patient's T cells (a type of immune system cell) are changed in the laboratory so they will attack cancer cells. T cells are taken from a patient's blood. Then the gene for a special receptor that binds to a certain protein on the patient's cancer cells is added to the T cells in the laboratory. The special receptor is called a chimeric antigen receptor. Large numbers of the CAR T cells are grown in the laboratory and given to the patient by infusion for treatment of certain cancers. Giving dasatinib and quercetin with cyclophosphamide, fludarabine and CAR-T cell therapy may kill more cancer cells in patients with relapsed or refractory multiple myeloma.

开始日期2025-05-15

申办/合作机构

Mayo Clinic

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100 项与 SRC family x YES1 相关的转化医学

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0 项与 SRC family x YES1 相关的专利（医药）

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项与 SRC family x YES1 相关的文献（医药）

2025-05-01·ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY

Liver organoids uncover tire-derived 6-PPDQ-induced hepatotoxicity of: A preliminary application of environmental toxicology and safety assessment

Article

作者: Zhang, Tianyi ; Luo, Kai ; Ge, Yiling ; Wei, Yuan ; Chen, Zaozao ; Zhang, Juan ; Pu, Yuepu ; Yang, Sheng ; Liang, Geyu

The novel pollutant, N-(1,3-dimethylbutyl)-N'-phenyl-p-phenylenediamine quinone (6-PPDQ) leaked out of the tire and has attracted extensive concerns due to its high lethal toxicity of salmon. However, the potential hepatotoxicity of 6-PPDQ exposure and its mechanisms are unknown. As a novel 3D cell culture, liver organoids (LOs) are more similar to real organ invitro in structure and function, which showed great potential for toxicity assessment. Herein, stable LOs were generated and their applicability on hepatotoxicity assessment was evaluated with four hepatotoxic compounds. The negative effect of 6-PPDQ was explored in LOs, live/dead staining visually demonstrated the damage to the liver, and the changes of ATP, LDH, ALT, and AST effectively reflected its hepatotoxicity. Meanwhile, machine learning-based quantitative assessments of LOs morphology changes provided objective data on area, circularity, and luminance changes, enabling sensitive detection of 6-PPDQ-induced hepatotoxicity. Furthermore, transcriptomic analysis revealed that the pathways related to DNA replication and repairment, cancers, and inflammation were significantly involved in the process of 6-PPDQ-induced liver injury; Disease enrichment analysis highlighted an increased risk of chronic liver diseases, and biliary atresia were validated by Cholyl-Lys-Fluorescein (CLF). Moreover, molecular docking analysis identified potential molecular targets of 6-PPDQ, including Slc6a9, Yes1, and Nos2. This study underscored the potential of LOs for toxicological studies and highlighted the toxic effects of 6-PPDQ on the liver, suggesting the need for further investigations to understand its long-term impact on human health.

2025-05-01·JOURNAL OF BIOLOGICAL CHEMISTRY

The Hippo pathway effector YAP inhibits NF-κB signaling and ccRCC growth by opposing ZHX2

Article

作者: Li, Xu ; Yang, Yingzi ; Liu, Yuchen ; Zhuo, Shu ; Han, Yuhong ; Zhou, Mengmeng ; Cho, Yong Suk ; Jiang, Jin

The prevailing view in the cancer field is that Hippo (Hpo) signaling pathway functions as a tumor suppressor pathway by blocking the oncogenic potential of the pathway effectors Yes1-associated transcriptional regulator (YAP)/transcriptional coactivator with PDZ-binding motif. However, YAP can also function as a context-dependent tumor suppressor in several types of cancer including clear cell renal cell carcinomas (ccRCCs). We find that, in addition to inhibiting hypoxia-inducible factor 2α, a major oncogenic driver in Von Hippel-Lindau-/- ccRCC, YAP also blocks nuclear factor κB (NF-κB) signaling in ccRCC to inhibit cancer cell growth under conditions where hypoxia-inducible factor 2α is dispensable. Mechanistically, YAP inhibits the expression of Zinc fingers and homeoboxes 2 (ZHX2), a Von Hippel-Lindau substrate and critical cofactor of NF-κB in ccRCC. Furthermore, YAP competes with ZHX2 for binding to the NF-κB subunit p65. Consequently, elevated nuclear YAP blocks the cooperativity between ZHX2 and the NF-κB subunit p65, leading to diminished NF-κB target gene expression. Pharmacological inhibition of Hpo kinase blocked NF-κB transcriptional program and suppressed ccRCC cell growth, which can be rescued by overexpression of ZHX2 or p65. Our study uncovers a crosstalk between the Hpo and NF-κB/ZHX2 pathways and its involvement in ccRCC growth inhibition, suggesting that targeting the Hpo pathway may provide a therapeutical opportunity for ccRCC treatment.

2025-04-01·Advanced Healthcare Materials

Interpenetrating Polymer Network Hydrogels with Tunable Viscoelasticity and Proteolytic Cleavability to Direct Stem Cells In Vitro

Article

作者: Fertala, Nicole ; Limasale, Yanuar Dwi Putra ; Lampel, Ayala ; Werner, Carsten ; Seth, Prannoy ; Freudenberg, Uwe ; Friedrichs, Jens ; Zhang, Yixin

Abstract:

The dynamic nature of cellular microenvironments, regulated by the viscoelasticity and enzymatic cleavage of the extracellular matrix, remains challenging to emulate in engineered synthetic biomaterials. To address this, a novel platform of cell‐instructive hydrogels is introduced, composed of two concurrently forming interpenetrating polymer networks (IPNs). These IPNs consist of the same basic building blocks – four‐armed poly(ethylene glycol) and the sulfated glycosaminoglycan (sGAG) heparin – are cross‐linked through either chemical or physical interactions, allowing for precise and selective tuning of the hydrogel's stiffness, viscoelasticity, and proteolytic cleavability. The studies of the individual and combined effects of these parameters on stem cell behavior revealed that human mesenchymal stem cells exhibited increased spreading and Yes‐associated protein transcriptional activity in more viscoelastic and cleavable sGAG‐IPN hydrogels. Furthermore, human induced pluripotent stem cell (iPSC) cysts displayed enhanced lumen formation, growth, and pluripotency maintenance when cultured in sGAG‐IPN hydrogels with higher viscoelasticity. Inhibition studies emphasized the pivotal roles of actin dynamics and matrix metalloproteinase activity in iPSC cyst morphology, which varied with the viscoelastic properties of the hydrogels. Thus, the introduced sGAG‐IPN hydrogel platform offers a powerful methodology for exogenous stem cell fate control.

项与 SRC family x YES1 相关的新闻（医药）

2025-03-29

·医药观澜

28款1类新药首次在中国获批临床！来自礼来、阿斯利康、科伦博泰、恒瑞医药等

▎药明康德内容团队报道根据中国国家药监局药品审评中心（CDE）官网以及公开资料梳理，本周（3月24日~3月29日），有28款1类创新药首次在中国获得临床试验默示许可（IND）。通过梳理，这些产品包括了小分子、抗体偶联药物（ADC）、放射性核素偶联药物（RDC）、抗体、多肽、AAV基因治疗药物、间充质干细胞药物、核酸类药物等类型。本文将根据公开资料介绍这些产品的基本信息。恩华药业：NH140068片作用机制：多种神经递质受体激动剂适应症：精神分裂症恩华药业1类新药NH140068片获批临床，拟开发治疗精神分裂症。根据恩华药业公告，NH140068是一款适于口服的多种神经递质受体激动剂，为新一代治疗精神分裂症的创新药。临床前试验结果表明，它可以激动多巴胺、5-羟色胺和痕量胺的相关受体，具有改善精神分裂症阳性和阴性症状且副作用小的潜力。科伦博泰：SKB107注射液作用机制：RDC药物适应症：晚期实体瘤骨转移科伦博泰1类新药SKB107注射液获批临床，拟开发用于晚期实体瘤骨转移。根据科伦博泰新闻稿，这是该公司与西南医科大学附属医院共同开发的靶向肿瘤骨转移的RDC药物，也是该公司首个进入临床阶段的核药项目。该产品以小分子作为靶向配体，搭配适宜的连接子、螯合剂和治疗用放射性同位素而组成。与传统外放射治疗相比，RDC药物SKB107可惠及全身多发骨转移患者，且靶向性强，能减少对正常组织的损伤，有望显示出良好的安全性。康诺亚：CM518D1作用机制：靶向CDH17的ADC适应症：实体瘤康诺亚申报的1类新药CM518D1获批临床，拟开发治疗实体瘤。公开资料显示，这是一款靶向CDH17的ADC。钙黏蛋白17（CDH17，又称CA17）是近年来胃肠道肿瘤治疗领域的一个新兴靶点。它是钙黏连蛋白家族中的成员，在超过50%的胃、胰腺、肝脏、食管至结直肠肿瘤组织中可检测到，研究表明其在多种肿瘤侵袭转移中发挥重要作用，尤其是在消化系统肿瘤中。华东医药：HDM3019作用机制：靶向OX40L和TNFα的双抗适应症：类风湿关节炎华东医药引进的1类新药HDM3019获批临床，拟开发治疗类风湿关节炎。这是一款靶向OX40L和TNFα的双特异性抗体。华东医药于2024年8月与IMBiologics达成独家许可协议，获得两款自身免疫性疾病新药在中国等37个亚洲国家的权益，其中就包括了这款IMB-101。该产品可参与调节炎症细胞因子，促进T细胞和浆细胞分化，以及自身抗体产生，维持免疫稳态平衡。映恩生物：注射用DB-2304作用机制：BDCA2靶向ADC适应症：系统性红斑狼疮映恩生物1类新药注射用DB-2304获批临床，拟开发治疗系统性红斑狼疮。根据映恩生物公开资料，这是其研发的潜在“first-in-class”针对自身免疫疾病的BDCA2靶向ADC。临床前研究表明，作为一款靶向BDCA2靶点的免疫调节型ADC，DB-2304除了具备抗体本身的治疗效果外，更叠加了小分子免疫抑制剂的强效调控效果，通过抗体端实现了靶点特异递送。在降低小分子免疫抑制剂系统暴露的同时，更高效广谱地抑制其它炎症因子的产生。映恩生物认为，该产品有希望成为首款针对系统性红斑狼疮（SLE）的ADC。阿斯利康：eneboparatide注射液作用机制：PTHR1激动剂适应症：慢性甲状旁腺功能减退症阿斯利康（AstraZeneca）在研的1类新药eneboparatide注射液获批临床，拟开发治疗慢性甲状旁腺功能减退症。公开资料显示，这是一款甲状旁腺激素受体1（PTHR1）激动剂多肽新药，它通过与PTHR1的特定构象结合，恢复PTH的功能，从而管理HypoPT患者的症状，同时保留肾功能和骨骼健康，旨在满足甲状旁腺功能减退症的治疗目标。阿斯利康此前以10.5亿美元收购罕见内分泌疾病领域生物技术公司Amolyt Pharma，从而获得这款产品。德睿智药：MRANK-106胶囊作用机制：WEE1/YES1双重激酶抑制剂适应症：晚期实体瘤德睿智药申报的1类新药MRANK-106胶囊获批临床，拟开发治疗晚期实体瘤。公开资料显示，这是一款口服WEE1/YES1双重激酶抑制剂，主要在实体瘤相关组织及肿瘤中富集而不是在血浆中，具有较高的组织/肿瘤靶向性。不同于传统的单靶点DNA损伤修复抑制剂，MRANK-106通过协同抑制WEE1和YES1两大关键蛋白，有望克服现有DNA损伤修复靶向治疗的局限性。礼来：注射用LY4052031作用机制：Nectin-4靶向ADC适应症：尿路上皮癌或其他实体瘤礼来（Eli Lilly and Company）申报的1类新药注射用LY4052031获批临床，拟单药用于治疗晚期或转移性尿路上皮癌或其他实体瘤。公开资料显示，这是一款在研的下一代抗Nectin-4 ADC，由Fc沉默的IgG1抗体通过可切割肽连接物偶联到新型拓扑异构酶I （TOPO 1）抑制剂camp98 （LSN3889710）组成，其具有更高的稳定性，DAR为8。与基于微管有效载荷的ADC相比，这种基于拓扑异构酶抑制剂的ADC具有潜在的优势。信念医药：BM-A101注射液作用机制：AAV基因治疗药物适应症：中度膝骨关节炎信念医药1类基因治疗药物BBM-A101注射液获批临床，拟开发治疗中度膝骨关节炎。根据信念医药新闻稿，该产品利用AAV载体将人源抗炎蛋白基因递送到患者膝关节持续表达，进而有望缓解关节腔内炎症，减轻膝骨关节炎患者的疼痛并改善膝关节功能，从而延缓疾病进程，最终改善膝骨关节炎患者的治疗结局。该产品有望实现“一次给药、长期有效”的膝骨关节炎治疗。中美瑞康：RAG-1C眼内注射液作用机制：小激活RNA药物适应症：增殖性玻璃体视网膜病变（PVR）中美瑞康在研的小激活RNA（saRNA）药物RAG-1C获批临床，拟开发用于治疗增殖性玻璃体视网膜病变（PVR）。RAG-1C通过RNAa机制上调细胞周期负性调控因子p21基因的表达，抑制视网膜色素上皮（RPE）细胞的异常增殖和迁移，从而阻止PVR的进展。PVR是孔源性视网膜脱离修复术后的一种严重并发症，以视网膜下和/或视网膜前纤维膜形成为特征，常导致视网膜再次脱离、最终可能导致严重的视力下降甚至失明。光谷中源药业：VUM03注射液作用机制：人脐带源间充质干/基质细胞新药适应症：非活动性/轻度活动性克罗恩病复杂性肛瘘根据光谷中源药业公开资料，VUM03注射液（人脐带源间充质干/基质细胞注射液）是由经筛选的健康新生儿脐带组织通过体外分离、扩增、收获、冻存后制备的人脐带源间充质干/基质细胞（UC-MSC）新药，为满足临床局部使用需求而开发的通用现货型细胞制剂，临床拟用于治疗非活动性/轻度活动性克罗恩病复杂性肛瘘。除了上述产品，本周首次在中国获批IND的1类新药还包括：中国科学院理化技术研究所和北京中科先行医疗科技有限公司联合申报的1类化药新药HB5凝胶，拟开发治疗皮肤鳞状细胞癌；众红生物申报的ZHB117舌下片，拟开发用于猫变应原过敏引起的成人过敏性鼻炎或鼻结膜炎（伴或不伴过敏性哮喘）的脱敏治疗；恒瑞医药申报的1类化药新药HRS-9190，拟开发用于全身麻醉诱导期气管插管及维持术中骨骼肌松弛；恒瑞医药申报的1类生物制品新药SHR-3792注射液，拟开发治疗实体瘤；谷冲医药申报的1类化药新药HB-48片，拟开发治疗复发胶质母细胞瘤（rGBM）；翰森制药申报的1类生物制品新药注射用HS-20108，拟开发治疗晚期实体瘤（如小细胞肺癌及神经内分泌肿瘤等）；翰森制药申报的1类生物制品新药注射用HS-20122，拟开发治疗晚期实体瘤（包括非小细胞肺癌、头颈部鳞状细胞癌或结直肠癌等）；海思科在研的小分子抑制剂1类新药HSK41959片，拟开发治疗MTAP缺失的晚期实体瘤；格物生物申报的1类化药新药GW5282片，拟开发治疗非霍奇金淋巴瘤；兴盟生物医药与科兴中维生物联合申报的SNA02-48注射液获批临床，拟作为被动免疫制剂，预防破伤风；信谱生物申报的1类生物制品新药XP-001-V2，拟开发治疗KRAS G12V突变的晚期实体瘤；罗氏（Roche）旗下基因泰克（Genentech）申报的1类新药RO7446603注射液，拟开发治疗糖尿病性黄斑水肿；美欧赛奥金生物申报的1类生物制品新药ZMPB-NK006注射液，拟用于治疗晚期或转移性恶性实体肿瘤；国健清科生物申报的1类新药人胎盘来源3D间充质干细胞注射液，拟用于治疗急性缺血性脑卒中；锦斯生物申报的1类新药GO306重组溶瘤痘苗病毒注射液，拟开发治疗实体瘤；青峰医药下属子公司江西科睿药业申报的1类化药新药KR230109乳膏，拟适用于寻常型痤疮患者的局部治疗；金赛药业申报的1类化药新药GenSci128片，拟开发治疗携带TP53 Y220C突变的局部晚期或转移性实体瘤。参考资料：[1]中国国家药监局药品审评中心（CDE）官网. Retrieved Mar 29，2025, From https://www.cde.org.cn/main/xxgk/listpage/4b5255eb0a84820cef4ca3e8b6bbe20c[2]各公司官网及公开资料本文来自药明康德内容团队，欢迎个人转发至朋友圈，谢绝媒体或机构未经授权以任何形式转载至其他平台。转载授权或其他合作需求，请联系wuxi_media@wuxiapptec.com。免责声明：药明康德内容团队专注介绍全球生物医药健康研究进展。本文仅作信息交流之目的，文中观点不代表药明康德立场，亦不代表药明康德支持或反对文中观点。本文也不是治疗方案推荐。如需获得治疗方案指导，请前往正规医院就诊。

抗体药物偶联物临床申请AACR会议申请上市临床1期

2025-03-28

·GlobeNewswire-Health Care

Nuvectis Pharma Announces Upcoming Presentations for NXP900 at the 2025 American Association for Cancer Research Meeting

March 26, 2025 -- Nuvectis Pharma, Inc. (NASDAQ: NVCT) ("Nuvectis" or the "Company"), a clinical-stage biopharmaceutical company focused on the development of innovative precision medicines for the treatment of serious conditions of unmet medical need in oncology, today announced upcoming presentations for NXP900 at the upcoming 2025 American Association for Cancer Research Meeting (2025 AACR), taking place from April 25th to April 30th in Chicago, IL. Nuvectis Pharma, Inc. is a biopharmaceutical company focused on the development of innovative precision medicines for the treatment of serious conditions of unmet medical need in oncology. The Company is currently developing two clinical-stage drug candidates, NXP800 and NXP900. NXP800 is an oral small molecule GCN2 activator currently in a Phase 1b clinical trial for the treatment for platinum resistant, ARID1a-mutated ovarian carcinoma and in an Investigator-sponsored clinical trial for the treatment of cholangiocarcinoma. NXP900 is an oral small molecule inhibitor of the SRC Family of Kinases (SFK), including SRC and YES1. NXP900's unique mechanism of action enables the inhibition of both the catalytic and scaffolding functions of the SRC kinase thereby providing complete shutdown of the signaling pathway. NXP900 is currently in a Phase 1a dose escalation study. The content above comes from the network. if any infringement, please contact us to modify.

AACR会议

2025-03-11

·BioBAY

研发动态丨德睿智药：自研WEE1/YES1双重抑制剂FDA获批

3月10日，BioBAY园内企业德睿智药宣布，其自主研发的潜在同类首创（First-in-Class）WEE1/YES1双重抑制剂MRANK-106已正式获得美国食品药品监督管理局（FDA）的新药临床批件（IND），准许开展针对多种实体瘤适应症的临床研究。 MRANK-106是一款口服WEE1/YES1双重激酶抑制剂，主要在实体瘤相关组织及肿瘤中富集而不是在血浆中，具有非常高的组织/肿瘤靶向性，有望降低WEE1相关选择性抑制剂的血液学高毒性，尤其适用于实体瘤的治疗。临床前显示在胰腺癌、小细胞肺癌、乳腺癌、结直肠癌、卵巢癌等癌症动物模型中单药疗效显著优于临床在研WEE1选择性抑制剂，并在联合治疗中展现出更优协同效应。该药物基于德睿智药自研知识图谱平台PharmKG™进行靶点筛选和发现，并利用AI驱动的Molecule Pro™平台优化分子设计，在生物学团队和药化团队紧密协作下高效发现了这一同类首创的候选药物分子。德睿智药创始人&CEO牛张明表示：“MRANK-106是公司在三年内第二款潜在进入临床阶段的自研药物，进一步验证了我们自研AI药物发现平台Molecule Pro™的顶尖能力及可延展性。团队将持续产出底层AI制药技术创新与突破性技术，不断输出兼具差异化和高临床价值的候选药物，让更多生命重获健康。” MRANK-106的IND获批，标志着德睿智药继GLP-1RA小分子口服新药MDR-001成功推进至IIb期临床研究后，又一款AI辅助设计药物进入临床开发阶段，这也是公司首个进入临床的同类首创候选药物（First-in-Class）。计划于2025年启动的I期临床试验将评估MRANK-106在晚期或转移性实体瘤患者中的安全性、耐受性、药代动力学特征和初步抗肿瘤活性。 ▌文章来源：德睿智药责编：何文正审核：任旭推荐阅读研发动态丨突破诺奖级别碱基修饰技术！艾博生物冻干mRNA疫苗获批临床研发动态丨同宜医药：CBP-1019获FDA授予快速通道资格研发动态丨士泽生物：全球首发通用细胞治疗渐冻症获美国FDA正式批准开展注册临床试验

临床申请临床1期快速通道疫苗信使RNA