更新于：2024-11-01

ITGA9

更新于：2024-11-01

基本信息

别名

ALPHA-RLC、Integrin alpha-9、Integrin alpha-RLC

+ [6]

简介

Integrin alpha-9/beta-1 (ITGA9:ITGB1) is a receptor for VCAM1, cytotactin and osteopontin. It recognizes the sequence A-E-I-D-G-I-E-L in cytotactin.

关联

项与 ITGA9 相关的药物

GND-001

靶点

ITGA9

作用机制

ITGA9拮抗剂

在研机构

Kaken Pharmaceutical Co., Ltd. [+1]

原研机构

Kidswell Bio Corp.

在研适应症

免疫系统疾病 [+1]

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

ASP-5094

靶点

ITGA9

作用机制

ITGA9拮抗剂

在研机构-

原研机构

Astellas Pharma, Inc.

在研适应症-

非在研适应症

类风湿关节炎

最高研发阶段无进展

首次获批国家/地区-

首次获批日期1800-01-20

项与 ITGA9 相关的临床试验

NCT03257852 / Completed临床2期

A Phase 2a, Randomized, Placebo-Controlled, Double-Blind, Parallel Group Study to Evaluate the Efficacy and Safety of ASP5094 in Patients With Rheumatoid Arthritis on Methotrexate

The objective of this study is to evaluate the efficacy, safety and pharmacokinetics of ASP5094 in patients with rheumatoid arthritis (RA) treated with background methotrexate (MTX).

开始日期2017-09-29

申办/合作机构

Astellas Pharma, Inc.

NCT02698657 / Completed临床1期

A Phase 1, Randomized, Placebo-controlled, Dose Escalation Study to Assess the Safety, Tolerability, and Pharmacokinetics of ASP5094 Following Multiple Intravenous Doses in Subjects With Rheumatoid Arthritis on Methotrexate

The purpose of this study is to evaluate the safety, tolerability and pharmacokinetics of multiple ascending intravenous doses of ASP5094 in male and female subjects with rheumatoid arthritis (RA) on methotrexate (MTX).

开始日期2016-02-23

申办/合作机构

Astellas Pharma Global Development, Inc.

100 项与 ITGA9 相关的临床结果

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100 项与 ITGA9 相关的转化医学

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0 项与 ITGA9 相关的专利（医药）

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268

项与 ITGA9 相关的文献（医药）

2024-11-01·Gene

Integrin-α9 overexpression underlies the niche-independent maintenance of leukemia stem cells in acute myeloid leukemia

Article

作者: Niibori-Nambu, Akiko ; Tergaonkar, Vinay ; Chooi, Jing Yuan ; Goh, Yufen ; Wang, Chelsia Qiuxia ; Yang, Henry ; Osato, Motomi ; Taniuchi, Ichiro ; Tham, Cheng-Yong ; Fam, Wee Nih ; Sonoki, Takashi ; Fullwood, Melissa Jane ; Suda, Toshio ; Hosoi, Hiroki ; Tan, Darren Qiancheng ; Tng, Jiaqi ; Chng, Wee Joo ; Chin, Desmond Wai Loon ; Nah, Giselle Sek Suan ; Li, Shang ; Takizawa, Hitoshi ; Cirovic, Branko ; Sashida, Goro

Leukemia stem cells (LSCs) are widely believed to reside in well-characterized bone marrow (BM) niches; however, the capacity of the BM niches to accommodate LSCs is insufficient, and a significant proportion of LSCs are instead maintained in regions outside the BM. The molecular basis for this niche-independent behavior of LSCs remains elusive. Here, we show that integrin-α9 overexpression (ITGA9 OE) plays a pivotal role in the extramedullary maintenance of LSCs by molecularly mimicking the niche-interacting status, through the binding with its soluble ligand, osteopontin (OPN). Retroviral insertional mutagenesis conducted on leukemia-prone Runx-deficient mice identified Itga9 OE as a novel leukemogenic event. Itga9 OE activates Akt and p38MAPK signaling pathways. The elevated Myc expression subsequently enhances ribosomal biogenesis to overcome the cell integrity defect caused by the preexisting Runx alteration. The Itga9-Myc axis, originally discovered in mice, was further confirmed in multiple human acute myeloid leukemia (AML) subtypes, other than RUNX leukemias. In addition, ITGA9 was shown to be a functional LSC marker of the best prognostic value among 14 known LSC markers tested. Notably, the binding of ITGA9 with soluble OPN, a known negative regulator against HSC activation, induced LSC dormancy, while the disruption of ITGA9-soluble OPN interaction caused rapid cell propagation. These findings suggest that the ITGA9 OE increases both actively proliferating leukemia cells and dormant LSCs in a well-balanced manner, thereby maintaining LSCs. The ITGA9 OE would serve as a novel therapeutic target in AML.

2024-03-06·The Journal of Maternal-Fetal & Neonatal Medicine4区 · 医学

Association study of hypertension susceptibility genes ITGA9, MOV10 , and CACNB2 with preeclampsia in Chinese Han population

4区 · 医学

Article

作者: Xin, Qian ; Ji, Qinghong ; Li, Li ; Sun, Wenjuan ; Jiang, Wen ; Duan, Shuhong ; Cheng, Ling ; Xin, Gang ; Wang, Jue ; Ma, Weihong ; Hong, Fanzhen ; Zhang, Ying ; Luan, Yun

OBJECTIVEPreeclampsia (PE) is a disorder that occurs during the pregnancy and could affect the maternal and perinatal mortality as well as morbidity. The aim of our study is to investigate the associations between the hypertension susceptibility genes ITGA9, MOV10 and CACNB2 with PE in Chinese Han population.METHODSA case-control study including 178 PE patients and 202 healthy controls was conducted to assess the associations between three loci (ITGA9 rs155524, MOV10 rs2932538 and CACNB2 rs4373814) and PE. The TaqMan probe assay was applied for genotyping in our study. Quantitative real-time PCR was performed to detect the mRNA expression levels of ITGA9, MOV10 and CACNB2. ELISA was carried out to detect the concentration of serum sFlt-1 or PLGF.RESULTSOur study detected no significant differences in allelic frequencies of three SNPs between PE patients and healthy controls. In the genetic model, the results showed that the patients with ITGA9 rs155524 GA or AA genotypes had a higher risk of PE development compared to those with GG genotype in codominant model. And PE patients had a higher frequency of GA + AA genotypes based on the dominant model. Subgroup analysis showed ITGA9 rs155524 was associated with early-onset PE but not with late-onset PE. No association was observed between MOV10 and CACNB2 with PE in any genetic model and subgroup analysis. Quantitative real-time PCR results showed that ITGA9 mRNA expression level was apparently increased in the placental tissues of PE patients. In addition, ITGA9 expression levels of GA + AA subjects were apparently higher than that in the genotype GG of placental tissues. sFlt-1/PLGF ratio was higher in GA + AA subjects than that in GG subjects. Regression analysis revealed that ratio of sFlt-1/PLGF was positively correlated with ITGA9 mRNA expression level.CONCLUSIONThis study has identified ITGA9 is a promising candidate susceptibility gene for early-onset PE. Our findings demonstrated that the high expression of ITGA9 might be associated with an increased risk of PE.

2024-01-01·Clinical and Translational Science

Expression pattern of osteopontin isoforms in malignant melanoma cell lines

Article

作者: Balázs, Margit ; Koroknai, Viktoria ; Szász, István ; Jámbor, Krisztina

AbstractOsteopontin (OPN) is a secreted integrin‐binding protein that plays a role in inflammation, cellular viability, cell adhesion and migration, cancer development, and diabetes through different mechanisms. The splice variants of OPN can play essential roles in cancer development, progression, and metastasis formation; however, limited data are available about the role of OPN isoforms in human malignant melanoma. Our goal was to define the gene expression patterns of five OPN variants (OPN4, OPN5, OPNa, OPNb, and OPNc), integrin, and CD44 receptor genes in primary and metastatic melanoma‐originated cell lines (n = 19), and to explore the association of the expression patterns with clinicopathological parameters. We evaluated the invasive property of the cell lines and investigated the potential association between the invasion and gene expression of OPN isoforms. We found a significant rise in the expression of OPNc in the invasive cell lines compared to the noninvasive cells and detected significantly higher expression of the OPN splice variants in melanoma cell lines originating from more advanced stages tumors than cell lines originating from early‐stage melanomas. The correlation analysis revealed that all five OPN variants positively correlated with ITGB3 and ITGA9, whereas OPN5 positively correlated with ITGB1, ITGAV, ITGA6, and CD44. OPN can activate extracellular signal‐regulated kinase signaling through binding to α9β1 integrin, promoting melanoma tumor cell migration. It is possible that such associations between OPN splice variants and integrin receptors may play a role in melanoma progression. In conclusion, our findings suggest that high expression of OPNc correlates with the invasive behavior of melanoma cells.

项与 ITGA9 相关的新闻（医药）

2022-07-25

·生物谷

Br J Pharmacol: SVEP1和整合素α4β1和α9β1在降低血管平滑肌细胞收缩中的新作用

血管张力由血管平滑肌细胞(VSMCs)的相对收缩状态调节。一些整合素通过L型电压门控钙通道(VGCC)调节钙内流，直接调节VSMC收缩。血管张力由血管平滑肌细胞(VSMCs)的相对收缩状态调节。一些整合素通过L型电压门控钙通道(VGCC)调节钙内流，直接调节VSMC收缩。编码整合素α9亚基α9β1的ITGA9和整合素α9β1的配体SVEP1的遗传变异与血压升高有关，然而，SVEP1和整合素α9β1都没有报道在血管调节中的作用。研究者确定了sVEP1和整合素α-9-β-1是否具有调节血管平滑肌细胞收缩的作用。图片来源: https://bpspubs.onlinelibrary.wiley.com/doi/10.1111/bph.15921 近日，来联合王国自莱斯特大学和国家健康研究所莱斯特生物医学研究中心的研究者们在Br J Pharmacol杂志上发表了题为“SVEP1 regulates GPCR-mediated vasoconstriction via integrin α9β1 and α4β1”的文章，该研究揭示了SVEP1和整合素α4β-1和α9β-1在降低血管平滑肌细胞收缩中的新作用。这可能为SVEP1和ITGA9基因座与血压风险的遗传关联提供解释。研究者使用免疫沉淀法和细胞结合实验证实SVEP1和整合素结合。人诱导多能干细胞来源的VSMCs用于体外[Ca~(2+)]i研究，Svep1+/-基因敲除小鼠模型的主动脉用于线状肌图术以测量血管收缩。研究者证实了SVEP1与整合素α9β1的连接，并发现SVEP1与整合素α4β1直接结合。研究者证实抑制SVEP1、整合素α4β1或α9β1可显著增加VSMC对GαQ/11-血管收缩药的[Ca~(2+)]i释放。与同窝小鼠相比，Svep1+/-小鼠的血管对U46619的收缩更大，或者当整合素α4β1或α9β1被抑制时，这种反应在整个血管中得到了证实。抑制研究表明，这种作用是通过VGCCs、PKC和Rho A/Rho激酶依赖的机制来实现的。 SVEP1调节GPCR介导的血管收缩U46619与Tax2R结合以激活GαQ和G12/13信号的拟议模型示意图图片来源: https://bpspubs.onlinelibrary.wiley.com/doi/10.1111/bph.15921 总之，本研究首次描述了细胞外基质蛋白SVEP1如何通过整合素α4β1和/或α9β1影响通过VGCC减少钙内流和降低钙敏感性的途径来降低血管平滑肌细胞的收缩能力，从而在细胞外环境和血管平滑肌细胞收缩之间提供了新的联系。（生物谷 Bioon.com）参考文献 Morris GE et al. SVEP1 regulates GPCR-mediated vasoconstriction via integrin α9β1 and α4β1. Br J Pharmacol. 2022 Jul 8. doi: 10.1111/bph.15921.

2021-05-03

·医药合作投融资联盟

新锐-放射治疗和诊断公司完成1100万美元A轮融资

2021年4月28日，温哥华市，Alpha-9 Theranostics Inc.宣布完成1100万美元的A轮融资，以推进新型放射治疗和诊断产品组合的发展。Longitude Capital领导了此次融资，BVF Partners L.P.和内部人士的参与融资。董事会主席Simon Pimstone博士说：“我们很高兴Longitude和BVF在Alpha-9上进行投资。” “这些高质量的投资者对我们的信念是放射疗法和诊断学。” Longitude Capital的医学博士David Hirsch表示：“ Alpha-9是一家令人兴奋的公司，由该领域的领导者创立，拥有越来越多的新颖资产。我们相信放射治疗学有潜力兑现精准肿瘤学的希望，我们期待与Alpha-9小组合作，将多个项目推进临床试验。” 关于Alpha-9 Alpha-9 Theranostics是一家临床阶段的放射性药物公司，致力于开发针对实体和血液恶性肿瘤的成像和治疗分子。利用专有技术和公司的专业知识，这些差异化分子具有以有利的安全性显着延长患者生命的潜力。Alpha-9由不列颠哥伦比亚大学和不列颠哥伦比亚大学癌症研究人员创立，旨在改善受转移性癌症影响的患者的生活。关于Longitude Capital Longitude Capital是一家领先的医疗保健风险投资公司，投资于寻求改善临床结果，改善生活质量并提高医疗保健效率的变革性生物技术，医疗技术和健康解决方案公司。Longitude Capital成立于2006年，通过多种投资方式投资于私营和上市公司。经度资本在加州门洛帕克，康涅狄格州格林威治和马萨诸塞州波士顿设有办事处。版权声明：本文转自医药合作投融资联盟，如不希望被转载的媒体或个人可与我们联系，我们将立即删除 ↓↓点击下方图片报名药融圈近期活动↓↓▲6.17-18 · 重庆 · 免费 · 创新制剂及改良型新药峰会，火热报名中▲8.10-11 苏州国际博览中心 · 免费 · 第三届CMC-China 万人大会，火热报名中▲5.11-12 · 广州 · 免费 · 新药峰会，即将开始【关于药融圈】药融圈围绕我国生物医药产业链，针对生物医药大数据、技术和资本投资、药融园(产业园)等开展系列系统性工作，促进我国生物医药产业健康发展，完善产业链，共同面对全球合作和竞争。点分享点点赞点在看