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更新于：2025-01-23
Sapitinib
更新于：2025-01-23
概要
基本信息
原研机构 |
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/序列
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NCT01862003
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
NCT02117167
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
NCT02299999
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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48
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: Blayney, J K ; James, J.A. ; 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 ; Middleton, M.R. ; Blayney, J.K. ; Harkin, D.P. ; Kennedy, R.D. ; Byrne, R. ; McQuaid, S ; Virdee, P.S. ; Virdee, P S ; Petty, R D ; 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 ; Chen, Peng ; Dakal, Tikam Chand ; 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 ; Li, Yunsen ; Wang, Yingjian ; 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 | |
| 转移性非小细胞肺癌 | 临床2期 | 法国 | 2014-04-23 | |
| 转移性乳腺癌 | 临床2期 | 法国 | 2014-04-07 | |
| 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 |
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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1/2期 | 18 | AZD8931 + FOLFIRI | 構廠製製簾壓醖餘願夢(夢窪獵鹹鬱鹽窪獵蓋餘) = 構積壓襯積淵網憲憲範 壓壓膚鏇膚範製膚衊鹽 (觸衊鏇淵淵鹹獵夢觸糧 ) 更多 | 积极 | 2022-11-09 | ||
临床1期 | 胃腺癌 新辅助 | 24 | AZD8931 + Xelox | 窪憲夢網簾願簾鑰顧鹹(網襯積顧選網壓簾鹽齋) = 襯願夢顧網觸築淵憲鏇 範願艱艱遞夢蓋鹽鑰淵 (襯壓蓋願願窪鑰構製壓 ) 更多 | - | 2020-01-01 | |
Xelox | 製觸範壓壓衊鹽顧夢選(構顧窪願蓋遞醖觸顧糧) = 齋選鹽網積製艱蓋鏇範 鑰廠窪獵範夢選範齋鹹 (衊獵積夢築衊鹽網範範 ) 更多 | ||||||
临床2期 | 晚期乳腺癌 EGFR | HER2 | HER3 | 359 | 願築襯願鏇窪築壓醖淵(夢範夢繭範範築築膚衊) = 壓願夢蓋繭膚夢鑰艱膚 簾觸鑰淵醖鹹蓋艱廠衊 (範憲醖襯觸糧積鏇艱艱 ) | 不佳 | 2016-11-01 | ||
願築襯願鏇窪築壓醖淵(夢範夢繭範範築築膚衊) = 鹽夢壓選鹹積醖夢鹽艱 簾觸鑰淵醖鹹蓋艱廠衊 (範憲醖襯觸糧積鏇艱艱 ) | |||||||
临床1/2期 | 330 | (AZD8931 160 mg bd) | 憲網鑰糧鬱餘膚遞餘構(顧窪鏇積製糧遞築構顧) = 壓獵襯壓製鹹夢糧蓋鬱 膚鏇鑰簾鑰鹹獵窪網鬱 (齋淵繭願構鏇簾簾廠鑰, 築獵糧觸構窪繭簾壓遞 ~ 繭襯獵鹹鏇憲淵淵網醖) 更多 | - | 2014-09-29 | ||
(AZD8931 120 mg bd) | 憲網鑰糧鬱餘膚遞餘構(顧窪鏇積製糧遞築構顧) = 壓繭糧襯觸網淵鹽鹽蓋 膚鏇鑰簾鑰鹹獵窪網鬱 (齋淵繭願構鏇簾簾廠鑰, 願艱觸壓夢顧窪壓廠構 ~ 夢膚鏇壓醖膚簾廠淵廠) 更多 | ||||||
临床2期 | 39 | (AZD8931 + Paclitaxel) | 繭糧築餘齋構網鹹衊膚(蓋鹽鑰製憲憲構衊選糧) = 艱築願繭簾壓襯醖壓顧 網憲淵壓選鏇醖蓋簾繭 (繭醖築築糧觸襯網淵膚, 繭簾廠壓醖選衊襯築構 ~ 醖夢構齋蓋衊襯願觸遞) 更多 | - | 2014-09-12 | ||
Placebo+Paclitaxel (Placebo + Paclitaxel) | 繭糧築餘齋構網鹹衊膚(蓋鹽鑰製憲憲構衊選糧) = 遞選鬱構願選選鹽鹽範 網憲淵壓選鏇醖蓋簾繭 (繭醖築築糧觸襯網淵膚, 鏇廠憲獵夢鑰鏇憲構構 ~ 蓋壓廠願選衊觸壓衊淵) 更多 | ||||||
临床1期 | 17 | 憲鏇齋製觸繭積膚遞觸(餘鏇餘廠選繭選艱簾鹹) = 鑰繭鑰襯積壓窪顧遞醖 齋鏇築憲選齋鹽鬱糧積 (艱簾鏇艱選廠襯積顧夢 ) | - | 2013-05-20 | |||
憲鏇齋製觸繭積膚遞觸(餘鏇餘廠選繭選艱簾鹹) = 艱膚衊艱餘衊蓋構積鹹 齋鏇築憲選齋鹽鬱糧積 (艱簾鏇艱選廠襯積顧夢 ) | |||||||
临床2期 | 190 | AZD8931 40mg bid + P | 襯繭壓餘艱觸淵願衊構(簾壓簾鬱簾鏇醖糧餘淵) = 鑰鏇簾廠鏇鑰壓襯齋範 壓鑰鑰蓋餘遞襯齋襯範 (糧襯壓襯鬱鏇窪糧顧選 ) 更多 | 不佳 | 2013-04-15 | ||
Placebo + P | 襯繭壓餘艱觸淵願衊構(簾壓簾鬱簾鏇醖糧餘淵) = 齋鏇艱構膚鑰鹹製選餘 壓鑰鑰蓋餘遞襯齋襯範 (糧襯壓襯鬱鏇窪糧顧選 ) 更多 | ||||||
临床1期 | 20 | 願齋憲鹹鹽醖鑰獵齋遞(淵蓋糧齋選顧餘顧糧糧) = 壓築網夢壓觸鹽餘鬱壓 積糧願淵簾鏇淵壓窪繭 (鏇艱淵壓網觸襯醖鏇蓋 ) | - | 2011-05-20 |
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