预约演示
更新于：2025-05-16
AZD-8186
更新于：2025-05-16
概要
基本信息
原研机构 |
权益机构- |
最高研发阶段临床1期 |
首次获批日期- |
最高研发阶段(中国)- |
特殊审评- |
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结构/序列
分子式C24H25F2N3O4 |
InChIKeyLMJFJIDLEAWOQJ-CQSZACIVSA-N |
CAS号1627494-13-6 |
关联
3
项与 AZD-8186 相关的临床试验NCT04001569
Phase1b/2 Study of AZD8186 in Combination With Paclitaxel in Patients With Advanced Gastric Cancer
NCT03218826
A Phase I Study of AZD8186 in Combination With Docetaxel in Patients With PTEN Mutated or PIK3CB Mutated Advanced Solid Tumors, Potentially Amenable to Docetaxel
NCT01884285
A Phase I, Open-label, Multicentre Study to Assess the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Preliminary Anti-tumour Activity of AZD8186 in Patients With Advanced Castration-resistant Prostate Cancer (CRPC), Squamous Non-Small Cell Lung Cancer (sqNSCLC), Triple Negative Breast Cancer (TNBC) and Patients With Known PTEN-deficient/Mutated or PIK3CB Mutated/ Amplified Advanced Solid Malignancies as Monotherapy and in Combination With Abiraterone Acetate or AZD2014
100 项与 AZD-8186 相关的临床结果
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100 项与 AZD-8186 相关的转化医学
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100 项与 AZD-8186 相关的专利（医药）
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69
项与 AZD-8186 相关的文献（医药）2025-06-01Journal of Bone Oncology
A novel bone metastasis-related gene signature for predicting prognosis, anti-androgen resistance, and drug choice in prostate cancer
Article
作者: Liu, Zhangcheng ; Han, Kun ; Luo, Yu ; Su, Shuai ; Song, Liangdong ; Wei, Chengcheng ; Deng, Xiaoqi ; Li, Yunfan ; Wang, Delin ; Zhang, Jindong
Objective:
Prostate cancer (PCa) often metastasizes to the bone, posing a significant clinical challenge. This study aims to develop a bone metastasis-related risk model for PCa.
Methods:
Bone metastasis-related genes (BMRGs) were identified through a combination of differential gene expression analysis and WGCNA using GSE32269 and GSE77930 datasets. Consensus clustering analysis was employed to determine the significance of these genes in molecular subtyping of PCa. LASSO-Cox regression analysis was utilized to construct the bone metastasis-related prognostic gene signature (BMRPS). The predictive performance of BMRPS was assessed using ROC curves, Kaplan-Meier survival curves, and a predictive nomogram. The immune landscape heterogeneity of subgroups was analyzed using CIBERSORT, ESTIMATE, and xCell algorithms. Drug sensitivity and molecular docking analysis were performed to identify drugs associated with BMRPS.
Results:
Forty-four BMRGs associated with the prognosis of PCa were identified. Consensus clustering revealed the pivotal role of these genes in stratifying PCa into three distinct prognostic clusters. The BMRPS, consisting of 14 BMRGs, demonstrated excellent predictive accuracy for prognosis and served as an independent prognostic factor in PCa. BMRPS effectively predicted the overall survival of bone metastatic PCa and differentiated bone metastasis from other metastatic types. BMRPS showed a close correlation with the immune landscape and immunotherapeutic response biomarkers. Additionally, BMRPS was associated with anti-androgen resistance, and AZD8186 was identified as a potential BMRPS-related drug that holds promise for personalized treatment in PCa.
Conclusion:
BMRPS facilitates the prediction of prognosis and resistance to anti-androgens in PCa. It also offers insights into the molecular mechanisms of bone metastasis and aids in drug selection for the treatment of PCa.
2025-03-01Nature Chemical Biology
A multiplex single-cell RNA-Seq pharmacotranscriptomics pipeline for drug discovery
Article
作者: Barker, Harlan ; Piki, Emilia ; Dini, Alice ; Sharma, Subodh ; Raivola, Juuli ; Ungureanu, Daniela ; Murumägi, Astrid
Abstract:
The gene-regulatory dynamics governing drug responses in cancer are yet to be fully understood. Here, we report a pipeline capable of producing high-throughput pharmacotranscriptomic profiling through live-cell barcoding using antibody–oligonucleotide conjugates. This pipeline combines drug screening with 96-plex single-cell RNA sequencing. We show the potential of this approach by exploring the heterogeneous transcriptional landscape of primary high-grade serous ovarian cancer (HGSOC) cells after treatment with 45 drugs, with 13 distinct classes of mechanisms of action. A subset of phosphatidylinositol 3-OH kinase (PI3K), protein kinase B (AKT) and mammalian target of rapamycin (mTOR) inhibitors induced the activation of receptor tyrosine kinases, such as the epithelial growth factor receptor (EGFR), and this was mediated by the upregulation of caveolin 1 (CAV1). This drug resistance feedback loop could be mitigated by the synergistic action of agents targeting PI3K–AKT–mTOR and EGFR for HGSOC with CAV1 and EGFR expression. Using this workflow could enable the personalized testing of patient-derived tumor samples at single-cell resolution.
2024-12-01Computational and Structural Biotechnology Journal
Integrating bulk RNA-seq and scRNA-seq analyses revealed the function and clinical value of thrombospondins in colon cancer
Article
作者: Ding, LiHui ; Chen, Juan ; Li, Jing ; Liu, Mingwei ; Tang, Ying ; Tian, Luyao ; Tang, Ao ; Long, Fei
Background:
Acting as mediators in cell-matrix and cell-cell communication, matricellular proteins play a crucial role in cancer progression. Thrombospondins (TSPs), a type of matricellular glycoproteins, are key regulators in cancer biology with multifaceted roles. Although TSPs have been implicated in anti-tumor immunity and epithelial-mesenchymal transition (EMT) in several malignancies, their specific roles to colon cancer remain elusive. Addressing this knowledge gap is essential, as understanding the function of TSPs in colon cancer could identify new therapeutic targets and prognostic markers.
Methods:
Analyzing 1981 samples from 10 high-throughput datasets, including six bulk RNA-seq, three scRNA-seq, and one spatial transcriptome dataset, our study investigated the prognostic relevance, risk stratification value, immune heterogeneity, and cellular origin of TSPs, as well as their influence on cancer-associated fibroblasts (CAFs). Utilizing survival analysis, unsupervised clustering, and functional enrichment, along with multiple correlation analyses of the tumor-microenvironment (TME) via Gene Set Variation Analysis (GSVA), spatial localization, Monocle2, and CellPhoneDB, we provided insights into the clinical and cellular implications of TSPs.
Results:
First, we observed significant upregulation of THBS2 and COMP in colon cancer, both of which displayed significant prognostic value. Additionally, we detected a significant positive correlation between TSPs and immune cells, as well as marker genes of EMT. Second, based on TSPs expression, patients were divided into two clusters with distinct prognoses: the high TSPs expression group (TSPs-H) was characterized by pronounced immune and stromal cell infiltration, and notably elevated T-cell exhaustion scores. Subsequently, we found that THBS2 and COMP may be associated with the differentiation of CAFs into pan-iCAFs and pan-dCAFs, which are known for their heightened matrix remodeling activities. Moreover, THBS2 enhanced CAFs communication with vascular endothelial cells and monocyte-macrophages. CAFs expressing THBS2 (THBS2+ CAFs) demonstrated higher scores across multiple signaling pathways, including angiogenic, EMT, Hedgehog, Notch, Wnt, and TGF-β, when compared to THBS2- CAFs. These observations suggest that THBS2 may be associated with stronger pro-carcinogenic activity in CAFs.
Conclusions:
This study revealed the crucial role of TSPs and the significant correlation between THBS2 and CAFs interactions in colon cancer progression, providing valuable insights for targeting TSPs to mitigate cancer progression.
100 项与 AZD-8186 相关的药物交易
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外链
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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 |
|---|---|---|---|---|
| 进展期胃腺癌 | 临床2期 | 韩国 | 2019-05-14 | |
| 实体瘤 | 临床2期 | - | - | |
| 晚期乳腺癌 | 临床1期 | 美国 | 2018-09-24 | |
| 晚期恶性实体瘤 | 临床1期 | 美国 | 2018-09-24 | |
| 晚期前列腺癌 | 临床1期 | 美国 | 2018-09-24 | |
| 转移性乳腺癌 | 临床1期 | 美国 | 2018-09-24 | |
| 转移性实体瘤 | 临床1期 | 美国 | 2018-09-24 | |
| 遗传性前列腺癌7型 | 临床1期 | 美国 | 2018-09-24 | |
| 不可切除的实体瘤 | 临床1期 | 美国 | 2018-09-24 | |
| 去势抵抗性前列腺癌 | 临床1期 | 美国 | 2013-07-09 |
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临床结果
临床结果
适应症
分期
评价
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临床1期 | 23 | (Dose Level 1) | 鏇鹹觸鹹製艱膚壓糧範(艱齋廠鹹積襯願艱鹹遞) = 艱觸鑰構齋願膚醖糧鏇 鹽襯觸製衊膚構壓醖齋 (鬱遞壓鑰淵齋糧廠製選, 1933.8) 更多 | - | 2023-09-21 | ||
(Dose Level -1) | 鹹襯衊簾蓋鏇遞獵積觸 = 鬱壓齋獵衊夢鹽繭鹽鬱 製繭餘齋選鏇鹹網膚願 (齋糧廠艱憲糧觸醖淵獵, 鑰廠鹽觸齋醖蓋繭願襯 ~ 艱簾繭顧鹽獵遞製願齋) 更多 | ||||||
临床1/2期 | 52 | abiraterone acetate+prednisone+AZD8186 | 網廠簾簾顧襯鑰網齋鹽(糧衊鬱積衊築衊餘範蓋) = diarrhoea (39%) and nausea (27%) 醖鬱壓製憲醖願餘鬱蓋 (壓衊醖鹹膚繭鑰蓋繭襯 ) 更多 | 积极 | 2018-10-22 | ||
临床1期 | 87 | 壓遞鬱鬱範餘壓壓窪廠(網襯網鑰網夢鹽觸憲繭) = 23 SAEs considered 餘範簾淵觸壓網醖鬱願 (艱醖鏇構築鏇艱選鑰蓋 ) 更多 | 积极 | 2017-06-05 | |||
N/A | - | - | 簾襯構膚糧憲簾積繭構(廠餘網構網鹹願鏇鏇衊) = 膚鏇築觸廠壓蓋繭鹹繭 餘觸鑰鹹壓築醖鏇淵顧 (鏇鹽遞鬱鏇壓簾廠製膚 ) | - | 2014-10-01 | ||
簾襯構膚糧憲簾積繭構(廠餘網構網鹹願鏇鏇衊) = 鬱餘廠鏇繭獵鹽觸襯壓 餘觸鑰鹹壓築醖鏇淵顧 (鏇鹽遞鬱鏇壓簾廠製膚 ) |
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