更新于：2024-09-19

HIPK2

更新于：2024-09-19

基本信息

别名

hHIPk2、HIPK2、homeodomain interacting protein kinase 2

+ [1]

简介

Serine/threonine-protein kinase involved in transcription regulation, p53/TP53-mediated cellular apoptosis and regulation of the cell cycle. Acts as a corepressor of several transcription factors, including SMAD1 and POU4F1/Brn3a and probably NK homeodomain transcription factors. Phosphorylates PDX1, ATF1, PML, p53/TP53, CREB1, CTBP1, CBX4, RUNX1, EP300, CTNNB1, HMGA1, ZBTB4 and DAZAP2. Inhibits cell growth and promotes apoptosis through the activation of p53/TP53 both at the transcription level and at the protein level (by phosphorylation and indirect acetylation). The phosphorylation of p53/TP53 may be mediated by a p53/TP53-HIPK2-AXIN1 complex. Involved in the response to hypoxia by acting as a transcriptional co-suppressor of HIF1A. Mediates transcriptional activation of TP73. In response to TGFB, cooperates with DAXX to activate JNK. Negative regulator through phosphorylation and subsequent proteasomal degradation of CTNNB1 and the antiapoptotic factor CTBP1. In the Wnt/beta-catenin signaling pathway acts as an intermediate kinase between MAP3K7/TAK1 and NLK to promote the proteasomal degradation of MYB. Phosphorylates CBX4 upon DNA damage and promotes its E3 SUMO-protein ligase activity. Activates CREB1 and ATF1 transcription factors by phosphorylation in response to genotoxic stress. In response to DNA damage, stabilizes PML by phosphorylation. PML, HIPK2 and FBXO3 may act synergically to activate p53/TP53-dependent transactivation. Promotes angiogenesis, and is involved in erythroid differentiation, especially during fetal liver erythropoiesis. Phosphorylation of RUNX1 and EP300 stimulates EP300 transcription regulation activity. Triggers ZBTB4 protein degradation in response to DNA damage. In response to DNA damage, phosphorylates DAZAP2 which localizes DAZAP2 to the nucleus, reduces interaction of DAZAP2 with HIPK2 and prevents DAZAP2-dependent ubiquitination of HIPK2 by E3 ubiquitin-protein ligase SIAH1 and subsequent proteasomal degradation (PubMed:33591310). Modulates HMGA1 DNA-binding affinity. In response to high glucose, triggers phosphorylation-mediated subnuclear localization shifting of PDX1. Involved in the regulation of eye size, lens formation and retinal lamination during late embryogenesis.

关联

项与 HIPK2 相关的药物

RLA-23174

靶点

HIPK2

作用机制

HIPK2 inhibitors

在研机构

上海璎黎药业有限公司

原研机构

上海璎黎药业有限公司

在研适应症

肾纤维化

非在研适应症-

最高研发阶段临床1期

首次获批国家/地区-

首次获批日期1800-01-20

Allosteric Inhibitor of HIPK2 (Shangpharma)

靶点

HIPK2

作用机制

HIPK2 inhibitors

在研机构

尚华医药

原研机构

尚华医药

在研适应症

肿瘤

非在研适应症-

最高研发阶段临床前

首次获批国家/地区-

首次获批日期1800-01-20

MU135

靶点

HIPK2

作用机制

HIPK2 inhibitors

在研机构

Masaryk University

原研机构

Masaryk University

在研适应症

肿瘤

非在研适应症-

最高研发阶段临床前

首次获批国家/地区-

首次获批日期1800-01-20

项与 HIPK2 相关的临床试验

CTR20241636 / Recruiting临床1期

随机、双盲、安慰剂平行对照、单次/多次口服、剂量递增评价RLA-23174片在健康受试者中的安全性、耐受性、药代动力学的I期临床试验

开始日期2024-05-13

申办/合作机构

上海璎黎药业有限公司

100 项与 HIPK2 相关的临床结果

登录后查看更多信息

100 项与 HIPK2 相关的转化医学

登录后查看更多信息

0 项与 HIPK2 相关的专利（医药）

登录后查看更多信息

512

项与 HIPK2 相关的文献（医药）

2024-12-31·Plant Signaling & Behavior

The 14-3-3 protein nt GF14e interacts with CIPK2 and increases low potassium stress in tobacco

Article

作者: Chen, Qian ; Mi, Qili ; Li, Xuemei ; Xiang, Haiying ; Li, Liqin ; Gao, Qian ; Lu, Yifei ; Jiang, Jiarui ; Lu, Liming ; Xu, Li ; Xu, Yong

Potassium (K⁺) plays a role in enzyme activation, membrane transport, and osmotic regulation processes. An increase in potassium content can significantly improve the elasticity and combustibility of tobacco and reduce the content of harmful substances. Here, we report that the expression analysis of Nt GF14e, a 14-3-3 gene, increased markedly after low-potassium treatment (LK). Then, chlorophyll content, POD activity and potassium content, were significantly increased in overexpression of Nt GF14e transgenic tobacco lines compared with those in the wild type plants. The net K⁺ efflux rates were severely lower in the transgenic plants than in the wild type under LK stress. Furthermore, transcriptome analysis identified 5708 upregulated genes and 2787 downregulated genes between Nt GF14e overexpressing transgenic tobacco plants. The expression levels of some potassium-related genes were increased, such as CBL-interacting protein kinase 2 (CIPK2), Nt CIPK23, Nt CIPK25, H⁺-ATPase isoform 2 a (AHA2a), Nt AHA4a, Stelar K⁺ outward rectifier 1(SKOR1), and high affinity K⁺ transporter 5 (HAK5). The result of yeast two-hybrid and luciferase complementation imaging experiments suggested Nt GF14e could interact with CIPK2. Overall, these findings indicate that NtGF14e plays a vital roles in improving tobacco LK tolerance and enhancing potassium nutrition signaling pathways in tobacco plants.

2024-11-01·International Immunopharmacology

Genipin 1-O-β-D-gentiobioside ameliorates CUMS-induced prefrontal cortex neuron neuronal apoptosis by modulating HIPK2 SUMOylation

Article

作者: Sun, Zhongwen ; Cui, Ruijie ; Chen, Zhuzi ; Sun, Ying ; Jiang, Yue ; Tao, Weiwei ; Xia, Changbo ; Zhao, Yan

BACKGROUNDDepression is a common mental illness with more than 280 million sufferers worldwide. Inflammation, particularly the c-Jun amino-terminal kinase (JNK) pathway, contributes to depression development and neuronal apoptosis. Gardenia is a herb with therapeutic effects on depression that has been shown to inhibit neuronal apoptosis. However, one of the components in gardenia, Genipin 1-O-β-D-gentiobioside(GG), has been less studied for its mechanism on depression. Thus, in the current study, we investigate how Genipin 1-O-β-D-gentiobioside improves depression and elucidate its possible mechanism of action.METHODSIn this investigation, we utilize a chronic unpredictable mild stress (CUMS) mouse model and corticosterone-induced primary cortical neurons to examine the role of GG in ameliorating depressive symptoms and neuronal apoptosis. TUNEL staining and flow cytometry assessed the effects of GG on neuronal apoptosis. Western Blot analyses and immunofluorescence assays apoptosis-related proteins in the prefrontal cortex and primary neurons. The site of action of GG in regulating homeodomain interacting protein kinase 2 (HIPK2) SUMOylation was further explored in primary neurons. We constructed siRNA-SUMO1 vectors to transfect primary neuronal cells with intracellular SUMO1 knockdown. Proximity ligation assay (PLA) experiments were performed on primary neurons according to the instructions of the assay kit to observe the physical relationship between HIPK2 and SUMO1. We predicted the HIPK2 SUMOylation modification site by an online database and constructed vectors to target and site-directed mutagenesis, then to transfected primary neuronal cells.RESULTSThe results showed that GG effectively alleviated depressive-like behaviours, down-regulated apoptosis-related proteins (p-JNK, Bax, Cleaved-Caspase-3), and inhibited neuronal apoptosis in CUMS-induced depressed mice and corticosterone-induced primary cortical neurons. We reveal a complex mechanism underlying the link between GG, SUMOylation of HIPK2, and complex pathways of neuronal apoptosis regulation. K326 and K1189 are the key SUMOylation sites regulated by GG in intricate interactions of apoptosis-related proteins.CONCLUSIONOur study demonstrated that GG exerts antidepressant-like actions through neuroprotective effects by inhibiting the apoptosis of prefrontal cortex neurons, revealing the mechanism of GG inhibition of JNK phosphorylation by enhancing HIPK2 SUMOylation.

2024-10-01·Experimental Neurology

Neuronal HIPK2-HDAC3 axis regulates mitochondrial fragmentation to participate in stroke injury and post-stroke anxiety like behavior

Article

作者: Sun, Shuaijie ; Li, Jun ; Zhu, Hongrui ; Peng, Li ; Yin, Tianyue ; Yang, Mengmeng ; Du, Yuhao ; Liu, Jinya ; Wang, Sheng

Post-stroke anxiety (PSA) seriously affects the prognosis of patients, which is an urgent clinical problem to be addressed. However, the pathological mechanism of PSA is largely unclear. Here, we found that neuronal HIPK2 expression was upregulated in the ischemic lesion after stroke. The upregulation of HIPK2 promotes Drp1 oligomerization through the HDAC3-dependent pathway, leading to excessive mitochondrial damage. This subsequently triggers the release of cellular cytokines such as IL-18 from neurons under ischemic stress. Microglia are capable of responding to IL-18, which promotes their activation and enhances their phagocytosis, ultimately resulting in the loss of synapses and neurons, thereby exacerbating the pathological progression of PSA. HIPK2 knockdown or inhibition suppresses excessive pruning of neuronal synapses by activated microglia in the contralateral vCA1 region to compromise inactivated anxiolytic pBLA-vCA1^Calb1+ circuit, relieving anxiety-like behavior after stroke. Furthermore, we discovered that early remimazolam administration can remodel HIPK2-HDAC3 axis, ameliorating the progression of PSA. In conclusion, our study revealed that the neuronal HIPK2-HDAC3 axis in the ischemic focus regulates mitochondrial fragmentation to balance inflammation stress reservoir to participate in anxiety susceptibility after stroke.

项与 HIPK2 相关的新闻（医药）

2024-05-20

·PRNewswire

Rila Therapeutics Announces Dosing of First Cohort in Phase 1 Clinical Trial of RLA-23174, a First-In-Class HIPK2 Allosteric Inhibitor, For Treatment of Chronic Kidney Disease and Fibrosis

SOUTH SAN FRANCISCO, Calif., May 20, 2024 /PRNewswire/ -- Rila Therapeutics, Inc., A biotechnology company focused on addressing the burden of chronic fibrotic diseases, today announced that the first cohort of subjects was dosed in a phase 1 trial of RLA-23174 in China in collaboration with our development partner, Yingli Pharmaceutical. RLA-23174 is a first-in-class small molecule allosteric inhibitor of HIPK2 which inhibits TGF-β signaling to address FSGS and other fibrotic diseases. The phase 1 placebo-controlled study for RLA-23174 is designed to assess its safety at multiple dose levels, tolerability, food effect, and pharmacokinetics. The single-center trial is enrolling healthy subjects and consists of staggered single ascending dose and multiple ascending dose cohorts. The trial will enroll up to 80 patients with expected completion by the end of 3Q2024 to support advancement into the Phase 2 clinical program. About RLA-23174 RLA-23174 is a new small molecule allosteric inhibitor of HIPK2 and a potential first-in-class treatment for pan-organ fibrosis. RLA-23174 inhibits the TGF-β/Smad3 signaling pathway by affecting the interaction between HIPK2 and Smad3, without inhibiting the kinase activity of HIPK2 or TGF-β receptor systems. Therefore, RLA-23174 exerts anti-fibrotic effects by reducing TGF-β signaling without serious adverse effects caused by complete HIPK2 or TGF-β signaling blockade. Preclinical studies have shown that RLA-23174 has superior anti-fibrotic effects, significant in vivo activity, excellent pharmacokinetic properties in animals, and a good safety profile. RLA-23174 demonstrates good druggability and excellent development potential. "Dosing of the first cohort in this first human study with RLA-23174 is a meaningful milestone for Rila Therapeutics. It signifies our evolution into a clinical development company bringing us closer to helping patients with kidney disease," stated Robert Drakas, Ph.D., Chief Executive Officer of Rila Therapeutics. "Regardless of several newly approved therapies for chronic kidney disease (CKD), many patients still progress to kidney failure, requiring dialysis or transplantation. Therefore, there is an urgent need to develop more effective drugs to halt disease progression, and we strongly believe that anti-fibrosis drug is one of the most promising drugs for such therapy. We are hopeful that HIPK2 inhibitor molecules/RLA-23174 could provide additional renal protection in conjunction with the current therapies for CKD. The Initiation of the phase 1 clinical trial of RLA-23174 is an important milestone for Rila. RLA-23174 exemplifies Rila's commitment to discovering and developing novel precision medicines for severe chronic kidney diseases," said founder John He, MD, PhD, Chief of Nephrology at Icahn Mount Sinai and key opinion leader at one of the largest medical centers in the US. About Rila Therapeutics Rila Therapeutics is focused on developing first-in-class medicines to treat fibrotic diseases. Rila was founded on exploring novel areas of biology focused on stopping fibrosis progression. Rila's programs target key molecular pathways whose dysfunction are hallmarks of renal fibrosis. Rila is building its pipeline by leveraging insights into the dynamic process of fibrosis progression to discover and develop therapeutics with differentiating mechanisms of action against fibrotic pathways. For more information, please visit SOURCE Rila Therapeutics

临床1期

2024-03-24

·药研发

【药研发0325】锐康迪微球优先审评 | 璎黎肾纤维化新药获批IND...

「本文共：15条资讯，阅读时长约：3分钟」今日头条锐康迪微球优先审评。Recordati集团旗下锐康迪医药「注射用双羟萘酸帕瑞肽微球」获CDE拟纳入优先审评，用于治疗无法手术或手术后未治愈和通过另一种生长抑素类似物治疗控制不佳的成人肢端肥大症患者。这是一款长效帕瑞肽产品（pasireotide pamoate），为第二代生长抑素类似物（SRL）。此前博鳌乐城维健罕见病临床医学中心已引进该产品应用于肢端肥大症患者的临床治疗。国内药讯1.益普生罕见病新药报产。Albireo公司与益普生开发的回肠胆汁酸转运蛋白（IBAT）抑制剂odevixibat胶囊（Bylvay）的上市申请获CDE受理。Odevixibat可阻断肠胆汁酸经过肠肝循环回流入肝，从而减轻肝脏内及循环内的胆汁酸浓度。去年11月，CDE已将该新药纳入优先审评，拟用于治疗6个月或以上患者的进行性家族性肝内胆汁淤积症（PFIC）。2.康方双抗亮相ELCC2024。康方生物与Summit公司联合开发的PD-1/VEG双抗ivonescimab在ELCC 2024年会上公布了治疗晚期或转移性非小细胞肺癌（NSCLC）的Ⅱ期临床AK112-201积极结果。数据显示，ivonescimab联合化疗在鳞状和非鳞状NSCLC患者中的中位PFS分别达到11.1个月（95% CI：9.5–16.3个月）和13.3个月（95% CI：8.3–16.4个月）。在中位随访时间为22.1个月后，两个患者亚组的中位总生存期均尚未达到。3.璎黎肾纤维化新药获批IND。璎黎药业1类化药RLA-23174片获国家药监局临床许可，拟开发用于治疗肾纤维化。RLA-23174是一款HIPK2变构抑制剂，通过影响HIPK2和Smad3之间的相互作用而不抑制HIPK2的激酶活性，从而仅抑制TGF-β/Smad3信号通路且不影响Smad2和p53的磷酸化。在临床前研究中，RLA-23174已显示出积极的抗纤维化效果和良好的安全性。4.石药又一款ADC获批临床。石药集团旗下巨石生物1类生物制品SYS6023获国家药监局临床许可，拟开发治疗晚期实体瘤患者。SYS6023是一款抗体偶联药物（ADC），可与肿瘤表面的特异性受体结合，通过内吞作用进入细胞并释放毒素，达到杀伤肿瘤细胞的作用。在临床前研究中，该产品对多种癌症均显示有较好的抗肿瘤作用。石药集团在ADC产品方面的靶点目前已涵盖了HER2、Nectin-4、Claudin 18.2、EGFR等。5.健康元引入COPD小分子新药。健康元与拜耳达成合作许可协议，获得后者一款小分子脯氨酰内肽酶（PREP）抑制剂在国内开发、商业化和生产的独家许可，应用于慢性阻塞性肺疾病（COPD）的治疗。该新药通过抑制PREP活性，有效阻止了COPD炎症介质的产生，有望为COPD患者提供新的治疗选择。该新药目前已在欧洲完成I期临床试验。国际药讯1.艾伯维卵巢癌ADC获批上市。艾伯维FRα靶向ADC新药Elahere（mirvetuximab soravtansine）获FDA由加速批准转换为完全批准，用于治疗叶酸受体α（FRα）阳性、铂类耐药的上皮性卵巢癌、输卵管癌或原发性腹膜癌患者。在Ⅲ期临床MIRASOL中，与化疗相比，Elahere联合治疗显著提高了患者总生存期（中位OS：16.46个月和12.75个月，p=0.0046），使死亡风险降低33%。2023年11月，艾伯维通过收购ImmunoGen公司获得该产品，华东医药拥有该药的大中华区权益。2.强生PAH组合疗法获批上市。强生单片剂组合疗法Opsynvi（M/T STCT，（马昔腾坦/他达拉非））获FDA批准上市，成为首款单片剂组合疗法，用于长期治疗WHO功能分级（FC）为II-III级的肺动脉高压（PAH）成人患者。在Ⅲ期A DUE临床中，与马昔腾坦或他达拉非单药治疗相比，M/T STCT治疗第16周显着降低了患者肺血管阻力（PVR），降幅达到39%（vs18%，p<0.0001）。3.诺华FIC新药获CHMP推荐上市。诺华补体B因子抑制剂Fabhalta（iptacopan）获欧盟人用药品委员会（CHMP）推荐批准，用于治疗患有溶血性贫血的成人阵发性睡眠性血红蛋白尿症（PNH）患者。在Ⅲ期临床APPLY-PNH中，在24周不需要输血的情况下，iptacopan治疗实现血红蛋白水平较基线增加2g/dL的患者比例达到82.3%；避免输血率达到94.8%。去年年底，该新药已获FDA批准上市，是首款PNH口服单药疗法。4.诺和诺德超长效胰岛素获CHMP支持上市。欧洲药品管理局人用药品委员会（CHMP）推荐批准诺和诺德每周1次超长效胰岛素icodec（Awiqli）上市，用于治疗成人糖尿病。在Ⅲa期临床ONWARDS中，与每日一次甘精胰岛素U100相比，每周一次icodec治疗具有非劣效性（P<0.001）和优效性（P=0.02），两组患者Hb1Ac水平的平均降幅分别为1.55%和1.35%，估计的组间差异为-0.19%，95% CI：-0.36~-0.03。目前，该新药也正接受FDA和CDE的上市监管审查。5.干眼症创新眼药水Ⅱ期临床积极。OKYO Pharma脂质偶联chemerin肽激动剂眼药水OK-101（0.05%）治疗干眼症（DED）的Ⅱ期临床结果积极。OK-101通过靶向G蛋白偶联受体ChemR23以启动眼部免疫细胞的抗炎症反应。数据显示，第15天时，OK-101治疗显著缓解了患者的眼痛症状，也显著改善了泪膜破裂时间；而且OK-101具有良好的滴眼舒适度，没有出现与药物相关的严重不良事件。6.卫材老年痴呆新药上市延期。卫材Aβ抗体lecanemab（仑卡奈单抗）上市申请被欧洲EMA推迟审批。EMA已取消在3月11日召开的神经科学咨询小组（SAG-N）会议上获得的关于lecanemab的积极建议，重新召开SAG-N会议再次审议lecanemab，以确保专家与该产品没有利益冲突。去年7月，FDA已批准lecanemab的加速上市许可转变为完成批准，用于治疗轻度阿尔茨海默症（AD）及相关轻度认知障碍（MCI）疾病。医药热点1.全球最贵药物易主。近日，Orchard公司对外公开其刚刚获批的早发性异染性脑白质营养不良（MLD）一次性基因疗法Lenmeldy在美国一次性治疗的批发采购成本（WAC）为425万美元（约合人民币3066万元）。而去年9月，外媒Fierce Pharma发布了2023年美国最昂贵药物排名TOP10，其中基因疗法占据半壁江山，最贵的为首款B型血友病基因疗法——UniQure公司的Hemgenix，定价350万美元。这也意味着Lenmeldy已登上最贵药物榜首。2.国家明文规定预制菜不添加防腐剂。3月21日，国家市场监管总局等六部门联合印发《关于加强预制菜食品安全监管促进产业高质量发展的通知》，明确规定预制菜中不添加防腐剂，规范预制菜范围，旨在强化预制菜食品安全监管。国家市场监督管理总局相关负责人回应，预制菜也称预制菜肴，预制菜虽经过工业化预制，但仍属于菜肴范畴，消费者在菜肴烹制过程中一般不添加防腐剂，规定预制菜中不添加防腐剂更加符合消费者期待。3.CDMO巨头「龙沙」拿下罗氏工厂。3月20日，全球CDMO巨头企业龙沙（Lonza）宣布，将以总交易金额额12亿美元收购罗氏位于美国瓦卡维尔（Vacaville）的大规模生物制药工厂。该厂是全球产量最大的生物制剂生产基地之一，生物反应器总容量约为33万升。龙沙计划投资约5亿瑞士法郎（约5.623亿美元），用于升级该设施并增强该基地的能力，以适应下一代哺乳动物生物药疗法。根据协议，该工厂的约750名员工将由龙沙提供就业机会，该工厂目前生产的产品也将继续由龙沙提供。评审动态 1. CDE新药受理情况（03月24日) 2. FDA新药获批情况（北美03月22日）股市资讯上个交易日 A 股医药板块 -1.18%涨幅前三跌幅前三万泽股份+10.04% 大理药业-10.02%永顺生物 +5.46% 龙津药业 -6.50%江苏吴中 +5.40% 粤万年青 -5.47%[舒泰神]公司收到关于多中心、随机、双盲、安慰剂平行对照I/11期探索BDB-001注射液治疗中重度化脓性汗腺炎患者的安全性和有效性的临床研究报告。取得III期临床研究总结报告。[贝达药业]产品BPI-221351片药物临床试验申请获得NMPA批准。[海思科]创新药HSK39297片新适应症拟用于治疗溶血性疾病获得药物临床试验批准通知书。[亿帆医药]控股子公司在研产品艾贝格司亭 a注射液(Ryzneuta®)获欧盟委员会批准上市。- The End -戳“阅读原文”，了解更多医药研发及股市资讯。

优先审批临床申请临床2期抗体药物偶联物申请上市

2024-03-23

·医药观澜

璎黎药业联合开发，创新HIPK2抑制剂在中国获批临床！

▎药明康德内容团队编辑3月22日，璎黎药业宣布其已收到中国国家药品监督管理局核准签发的《药物临床试验批准通知书》，批准该公司开展新型小分子HIPK2变构抑制剂RLA-23174片治疗肾纤维化的临床试验。HIPK是定位于细胞核内的丝氨酸/苏氨酸蛋白激酶，表达于多种组织中，包括大脑、肺、肝、肾、皮肤、肌肉等。HIPK家族有四个直系同源物，称为HIPK1、HIPK2、HIPK3、HIPK4。在HIPK家族中，HIPK2与纤维化关系密切，如心肌结构重建、肝脏纤维化、肺纤维化，肾脏纤维化等，是研究抗纤维化治疗的重要靶点。RLA-23174是璎黎药业和Rila Therapeutics公司合作开发的一种新型小分子HIPK2变构抑制剂。该候选药可通过影响HIPK2和Smad3之间的相互作用来抑制TGF-β/Smad3信号通路，不抑制HIPK2的激酶活性，从而不影响Smad2和p53的磷酸化。由此RLA-23174在发挥抗纤维化作用的同时，还能减少因抑制HIPK2而产生的多种不良反应。临床前研究表明，RLA-23174具有良好的抗纤维化效果、很高的体内外活性、优良的动物体内药代特性和良好的安全性。璎黎药业研发总裁兼上海璎黎总经理许祖盛博士表示：“目前对HIPK2影响肾纤维化的发病机制的认识已取得重要进展，但还没有相应发病机制的新药进入临床研究阶段，临床上非常缺乏针对肾纤维化的有效治疗药物。此次RLA-23174获批临床进入临床研究后，公司将积极推进其临床试验的开展，尽早地为肾纤维化病人提供治疗选择。”参考资料：[1]璎黎药业首个联合开发合作项目-全球新靶点HIPK2抑制剂RLA-23174获得中国临床试验许可. Retrieved Mar 22, 2024. From https://mp.weixin.qq.com/s/WIF_Ml3Y49QDcNgZQ9jVWg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。转载授权请在「医药观澜」微信公众号留言联系我们。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。

申请上市临床1期