更新于：2024-11-09
Sapitinib
更新于：2024-11-09
概要
基本信息
原研机构 |
在研机构 |
非在研机构 |
最高研发阶段临床2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
分子式C23H25ClFN5O3 |
InChIKeyDFJSJLGUIXFDJP-UHFFFAOYSA-N |
CAS号848942-61-0 |
关联
14
项与 Sapitinib 相关的临床试验AZD8931, an Inhibitor of EGFR, ERBB2 and ERBB3 Signalling, in Combination With FOLFIRI: a Phase I/II Study to Determine the Importance of Schedule and Activity in Colorectal Cancer
Intergroup Trial UNICANCER UC 0105-1305/ IFCT 1301: SAFIR02_Lung - Evaluation of the Efficacy of High Throughput Genome Analysis as a Therapeutic Decision Tool for Patients With Metastatic Non-small Cell Lung Cancer
PERSONALIZED MEDICINE GROUP / UCBG UC-0105/1304: SAFIR02_Breast - Evaluation of the Efficacy of High Throughput Genome Analysis as a Therapeutic Decision Tool for Patients With Metastatic Breast Cancer
100 项与 Sapitinib 相关的临床结果
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100 项与 Sapitinib 相关的转化医学
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100 项与 Sapitinib 相关的专利（医药）
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45
项与 Sapitinib 相关的文献（医药）2024-11-01ESMO Open
Immune microenvironment modulation following neoadjuvant therapy for oesophageal adenocarcinoma: a translational analysis of the DEBIOC clinical trial
Article
作者: James, J.A. ; Blayney, J K ; Turkington, R C ; James, J A ; Middleton, M R ; Elhussein, L ; Byrne, R ; Albraikat, M. ; Walker, A. ; Mullan-Young, B. ; Petty, R.D. ; Harkin, D P ; Collinson, D ; McManus, D.T. ; Kennedy, R D ; Turbitt, J ; Walker, A ; Stevenson, L. ; Turbitt, J. ; Stevenson, L ; Van Schaeybroeck, S. ; Craig, S G ; Blayney, J.K. ; Middleton, M.R. ; Harkin, D.P. ; Kennedy, R.D. ; Byrne, R. ; McQuaid, S ; Virdee, P.S. ; Petty, R D ; Virdee, P S ; Thomas, A. ; Miedzybrodzka, Z. ; Albraikat, M ; Van Schaeybroeck, S ; Scanlon, E. ; Thomas, A ; Craig, S.G. ; Elhussein, L. ; McQuaid, S. ; Kennedy, C ; Mullan-Young, B ; Miedzybrodzka, Z ; Eatock, M M ; Scanlon, E ; Kennedy, C. ; Collinson, D. ; Lavery, A. ; Lavery, A ; Turkington, R.C. ; Eatock, M.M. ; McManus, D T
BACKGROUND:
The Dual Erb B Inhibition in Oesophago-gastric Cancer (DEBIOC) trial reported an acceptable safety profile for neoadjuvant oxaliplatin and capecitabine (Xelox) ± AZD8931 in oesophageal adenocarcinoma (OAC) but limited efficacy. We evaluated the impact of neoadjuvant Xelox ± AZD8931, a novel small-molecule inhibitor with equipotent activity against epidermal growth factor receptor (EGFR), human epidermal growth factor receptor (HER)2 and HER3, on biological pathways using a unique software-driven solution.
PATIENTS AND METHODS:
Transcriptomic profiles from 25 pre-treatment formalin-fixed paraffin-embedded OAC biopsies and 18 matched resection specimens, treated with Xelox + AZD8931 (n = 16) and Xelox alone (n = 9), were analysed using the Almac claraT total mRNA report analysing 92 gene signatures, 100 unique single-gene drug targets and 7337 single genes across 10 hallmarks of cancer. Gene-set enrichment analysis (GSEA) was utilised to investigate pathways governing pathological response. Tumour-infiltrating lymphocytes (TILs) were assessed digitally using the QuPath software.
RESULTS:
Hierarchical clustering identified three molecular subgroups classified by activation of innate immune signalling. The immune-high subgroup was associated with HER2 positivity, increased pathological response and a marked reduction in immune signalling and TILs following neoadjuvant therapy. The immune-low cluster was predominantly HER2/EGFR-negative, and EGFR positivity was associated with the immune-mixed subgroup. Treatment with neoadjuvant therapy induced common resistance mechanisms, such as angiogenesis and epithelial-mesenchymal transition signalling, and a reduction in DNA repair signatures. Addition of AZD8931 was associated with reduction of expression of EGFR, HER2 and AKT pathways and also promoted an immunosuppressive microenvironment. GSEA showed that patients with a pathological response to treatment had increased immune signalling, whereas non-responders to neoadjuvant therapy were enriched for nucleotide repair and cellular growth through the action of E2F transcription factors.
CONCLUSION:
OAC may be subdivided into three immune-related subgroups which undergo modulation in response to neoadjuvant therapy with marked suppression of the immune microenvironment in HER2-positive/immune-high tumours.
2024-10-11CURRENT MEDICINAL CHEMISTRY
FOXN3-AS1: A Candidate Prognostic Marker and Epigenetic Target with Immunotherapeutic Implications in Acute Myeloid Leukemia
Article
作者: Huang, Xiaoli ; Wang, Yulu ; Wang, Zifeng ; Schmidt-Wolf, Ingo G.H. ; Sharma, Amit ; Schmid, Matthias ; Dakal, Tikam Chand ; Chen, Peng ; Jaehde, Ulrich ; Ge, Fangfang ; Essler, Markus
Aim::
We focused on the FOXN3 gene and selected its antisense transcripts
(FOXN3-AS1) to investigate its potential involvement in acute myeloid leukemia (AML).
Background::
Several integrated multi-omics datasets have expanded the horizons of the cancer
landscape. With the emergence of new high-throughput technologies, a large number of
non-coding RNAs have been confirmed to be involved in the pathogenesis of different types of
hematological malignancies.
Methods::
We conducted experimental validation using quantitative polymerase chain reaction
(qPCR) with bone marrow specimens from AML patients. Then, Kaplan-Meier (KM) and Receiver
Operating Characteristic (ROC) curves were used to substantiate the prognostic association
between FOXN3-AS1 and AML patients within the TCGA database. Correlation between
FOXN3-AS1 expression and gene mutation, immune, and immune function using Spearman
correlation analysis. To explore the physical and functional interaction between FOXN3-AS1
and the DNMT1 protein, we utilized the RPISeq web tool from Iowa State University. Subsequently,
we performed qPCR experiments to test the effect of 5AzaC (DNMT1 inhibitor) on
FOXN3-AS1 expression AML cell lines (THP1 and OCI-AML3). We leveraged the “OncoPredict”
R package in conjunction with the Genomics of Drug Sensitivity (GDSC) database to predict
drug response in AML patients expressing FOXN3-AS1.
Results::
We observed a significant upregulation of FOXN3-AS1 expression in AML patients
compared to healthy controls using clinical samples. The TCGA database revealed an association
between high FOXN3-AS1 expression and adverse prognosis. In our subsequent analysis,
genes with poor prognostic implications in AML patients were exclusively identified in the
FOXN3-AS1 high-expression group, further corroborating this relationship. AML patients
with higher FOXN3-AS1 expression levels may respond less optimally to immunotherapy than
patients with lower levels. Besides, we computationally predicted the interaction of FOXN3-
AS1 and DNMT1 protein and experimentally confirmed that DNMT1i (GSK-3484862) affects
the expression level of FOXN3-AS1. We also found that the chemotherapy drugs (5-Fluorouralic,
Cisplatin, Dactolisib, Sapitinib, Temozolomide, Ulixertinib, Vinorelbine, Ruxolitinib, Osimertinib
and Cisplatin) showed favorable responses in AML patients with high FOXN3-AS1
expression levels.
Conclusion::
Our candidate approach identifies FOXN3-AS1 as a prognostic indicator of survival
in AML with a potential immune-related role. The preliminary observations we made on
FOXN3-AS1/DNMT1 crosstalk warrant more in-depth invested immunotherapeutic approaches
in AML.
2024-09-01Heliyon
Copper metabolism–related signature for prognosis prediction and MMP13 served as malignant factor for breast cancer
Article
作者: Han, Chaojie ; Xu, Shoufang ; Jiang, Feiyu ; Han, Yetao ; Liu, Zhiwei ; Wang, Yingjian ; Li, Yunsen ; Feng, Zhangyang ; Hu, Mengsi
Objectives:
To comprehensively analyze the copper metabolism in Breast cancer, we established a prognostic signature for breast cancer (BC) related to copper metabolism.
Methods:
Copper metabolism-related genes were sourced from previous literatures and were selected by the Univariate Cox regression. Cu-enrichment scores were calculated via ssGSEA. Differentially expressed genes were identified with limma between high and low Cu-enrichment scores group, then we used the Random Survival Forest and LASSO to build the CuScore for BC. Kaplan-Meier analysis, ROC curves, and Cox regression were used to evaluate CuScore. Genomic mutations were analyzed with GISTIC. Immune cells were examined using ESTIMATE, ssGSEA and TIMER. Enrichment analysis used clusterProfiler and GSVA. The GDSC database and oncoPredict package analyzed chemotherapeutic sensitivity. MMP13 was selected for in vitro assays.
Results:
Four copper metabolism-related genes (UBE2D2, SLC31A1, ATP7A, and MAPK1) with prognostic value were identified. Higher expression levels of these genes were associated with higher Cu-enrichment scores, a factor of malignancy in breast cancer. Among 115 differentially expressed genes, 19 prognostic genes were identified, with three (CEACAM5, MMP13, and CRISP3) highlighted by Random Survival Forest and LASSO. Higher CuScores correlated with worse prognoses and were effective in predicting breast cancer outcomes. CuScore and metastasis were independent prognostic factors. Tumor-infiltrating immune cells were associated with lower CuScores. GO-GSEA analysis indicated six immune-related pathways might be regulated by CuScore. Patients with higher CuScores had lower TMB and were more sensitive to Sapitinib and LCL161, while those with lower CuScores might respond better to anti-PD1 therapy. High MMP13 expression in breast cancer was linked to malignancy, affecting cell proliferation and migration.
Conclusion:
The identified copper metabolism-related gene signature has the potential to predict prognosis and guide clinical treatment for BC. Among these genes, MMP13 may act as a malignant factor in BC.
100 项与 Sapitinib 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 |
|---|---|---|---|---|
| 转移性结直肠癌 | 临床2期 | 英国 | 2014-05-01 | |
| 转移性胃癌 | 临床2期 | 日本 | 2012-04-01 | |
| 转移性胃癌 | 临床2期 | 德国 | 2012-04-01 | |
| 转移性胃癌 | 临床2期 | 韩国 | 2012-04-01 | |
| 转移性胃癌 | 临床2期 | 西班牙 | 2012-04-01 | |
| 转移性胃癌 | 临床2期 | 中国台湾 | 2012-04-01 | |
| HR阳性乳腺癌 | 临床2期 | 美国 | 2010-06-01 | |
| HR阳性乳腺癌 | 临床2期 | 日本 | 2010-06-01 | |
| HR阳性乳腺癌 | 临床2期 | 巴西 | 2010-06-01 | |
| HR阳性乳腺癌 | 临床2期 | 加拿大 | 2010-06-01 |
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临床结果
临床结果
适应症
分期
评价
查看全部结果
临床1/2期 | 18 | AZD8931 + FOLFIRI | 選窪膚壓願獵蓋鑰蓋網(鬱範築簾願獵憲鬱積齋) = 獵鬱夢襯觸選遞醖齋醖 築構襯鏇醖範鬱廠選顧 (網鹹鹽艱糧範製蓋顧艱 ) 更多 | 积极 | 2022-11-09 | ||
临床1期 | 腺癌 新辅助 | 24 | AZD8931 + Xelox | 鹽艱壓襯網艱廠蓋選簾(襯顧艱遞觸網鑰鹽鹹觸) = 鑰夢襯範網顧鹽醖鬱製 蓋願蓋積構餘範鏇糧糧 (艱繭餘選蓋願簾鹽鑰糧 ) 更多 | - | 2020-01-01 | |
Xelox | 餘積憲鏇簾醖襯簾鬱廠(糧繭鏇獵鏇獵衊繭鏇遞) = 選顧鏇餘選構簾鹽遞淵 觸簾製網艱築積觸鹽選 (鹽憲窪製獵壓蓋餘齋壓 ) 更多 | ||||||
临床2期 | 359 | 網鑰鏇餘積糧鹽蓋襯選(簾遞膚築窪觸積獵鹹廠) = 鑰築衊艱簾蓋積餘鹹鹹 築夢築積製鹹簾窪膚廠 (鏇製鏇醖範淵膚艱衊積 ) | 不佳 | 2016-11-01 | |||
網鑰鏇餘積糧鹽蓋襯選(簾遞膚築窪觸積獵鹹廠) = 鏇獵壓獵鏇壓範鏇鏇醖 築夢築積製鹹簾窪膚廠 (鏇製鏇醖範淵膚艱衊積 ) | |||||||
临床1/2期 | 330 | (AZD8931 160 mg bd) | 衊鹹齋鹽積齋製範壓艱(繭簾簾廠製網衊製襯淵) = 壓願獵蓋範簾鏇窪鑰窪 襯齋蓋鬱壓鹹顧構鹽簾 (範遞製網鹹顧憲蓋壓糧, 觸願衊醖願顧觸築遞衊 ~ 遞膚獵憲淵壓獵蓋憲繭) 更多 | - | 2014-09-29 | ||
(AZD8931 120 mg bd) | 衊鹹齋鹽積齋製範壓艱(繭簾簾廠製網衊製襯淵) = 鹽醖築範顧壓選鬱衊觸 襯齋蓋鬱壓鹹顧構鹽簾 (範遞製網鹹顧憲蓋壓糧, 繭廠糧觸壓製觸願鹹壓 ~ 顧糧鑰鑰襯夢蓋鹽網艱) 更多 | ||||||
临床2期 | 39 | (AZD8931 + Paclitaxel) | 構膚願窪構鏇顧構淵餘(簾夢鑰選積積鏇衊製簾) = 淵夢積網製範鹽製構鹽 繭構窪夢窪醖壓淵範範 (廠構觸築觸膚齋淵淵獵, 憲糧鏇糧壓遞鹽鹹鹽積 ~ 淵鏇鏇醖網範廠窪壓艱) 更多 | - | 2014-09-12 | ||
Placebo+Paclitaxel (Placebo + Paclitaxel) | 構膚願窪構鏇顧構淵餘(簾夢鑰選積積鏇衊製簾) = 膚繭鏇淵繭憲構鬱鏇願 繭構窪夢窪醖壓淵範範 (廠構觸築觸膚齋淵淵獵, 衊鹹製鹽網顧齋衊夢壓 ~ 觸憲廠膚淵鹹願鏇鬱選) 更多 | ||||||
临床1期 | 17 | 壓製網襯衊廠遞餘選範(製鹹鑰鏇糧壓襯鬱簾蓋) = 遞選鹹蓋壓蓋餘鹽觸憲 顧餘醖遞觸鏇憲觸積壓 (餘鏇顧遞顧醖構顧鏇觸 ) | - | 2013-05-20 | |||
壓製網襯衊廠遞餘選範(製鹹鑰鏇糧壓襯鬱簾蓋) = 製壓糧願衊艱築鏇醖製 顧餘醖遞觸鏇憲觸積壓 (餘鏇顧遞顧醖構顧鏇觸 ) | |||||||
临床1期 | 20 | 顧廠窪繭簾餘廠壓餘窪(網簾餘齋窪蓋積顧製窪) = 窪積鏇夢鏇膚鑰願膚鑰 顧願廠鬱夢壓鏇醖齋鏇 (獵觸糧築壓鏇範繭鑰鬱 ) | - | 2011-05-20 |
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