Refametinib(Refametinib) - 药物靶点：MEK1 x MEK2_专利_临床

概要

基本信息

药物类型

小分子化药

别名

+ [6]

靶点

MEK1 x MEK2

作用方式

抑制剂

作用机制

MEK1抑制剂(双特异性丝裂原活化蛋白激酶激酶1抑制剂)、MEK2抑制剂(双特异性丝裂原活化蛋白激酶激酶2抑制剂)

治疗领域

肿瘤消化系统疾病内分泌与代谢疾病

在研适应症-

非在研适应症

晚期癌症肝细胞癌恶性实体肿瘤+ [2]

原研机构

Bausch Health Americas, Inc.

在研机构-

非在研机构

拜耳医药保健有限公司

Bayer AGBayer Schering Pharma AG

权益机构

Bayer Pharma AG

Ardea Biosciences, Inc.

最高研发阶段终止临床2期

首次获批日期-

最高研发阶段(中国)无进展

特殊审评特殊审批 (中国)

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结构/序列

分子式C19H20F3IN2O5S

InChIKeyRDSACQWTXKSHJT-NSHDSACASA-N

CAS号923032-37-5

关联

14

项与 Refametinib 相关的临床试验

NCT02346032

/ Completed临床2期IIT

Phase II Study of Refametinib, a MEK Inhibitor, as Second-line Treatment in Advanced Biliary Tract Adenocarcinoma

Phase II Study of Refametinib, a MEK inhibitor, as second-line treatment in advanced biliary tract adenocarcinoma

开始日期2015-06-30

申办/合作机构

Samsung Medical Center

CTR20140453

/ Completed临床2期

RAS突变肝细胞癌患者中，研究药与索拉非尼联合用一线治疗的一项二期前瞻性单臂多中心非对照开放性研究

该研究的主要目的是：在有KRAS或NRAS突变的不可切除或转移性HCC患者中，评估Refametinib联合索拉非尼的有效性。次要目的是：在有KRAS或NRAS突变的不可切除或转移性HCC患者中，评估Refametinib联合索拉非尼的安全性。其它目的为：分析生物标志物、药代动力学（PK）和患者报告结局（PRO，仅第2阶段）。

开始日期2015-03-04

申办/合作机构

Bayer Pharma AG

[+1]

EUCTR2014-002460-33-IT

/ Unknown statusN/AIIT

ANTI MEK THERAPY WITH REFAMETINIB TO PREVENT RESISTANCE TO EGFR-TARGETED TREATMENT IN METASTATIC COLORECTAL CANCERS - ARES

开始日期2014-10-23

申办/合作机构-

100 项与 Refametinib 相关的临床结果

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100 项与 Refametinib 相关的转化医学

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100 项与 Refametinib 相关的专利（医药）

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190

项与 Refametinib 相关的文献（医药）

2025-02-01·Cancer Biomarkers

Bioinformatics screened of biomarkers for the prognosis of hepatocellular carcinoma

Article

作者: Sun, Lin ; Hu, Guiling ; Gao, Wentao ; Liu, Tingting ; Wei, Jianshe ; Ma, Xiaoping ; Bao, Chunxu

BackgroundThis study aimed to identify hub genes linked to hepatocellular carcinoma (LIHC) pathogenesis using bioinformatics analysis.MethodA total of 3865 samples from 12 datasets in the HCCDB database were analyzed to identify prognostic expression genes (PDGs). Enrichment analysis using DAVID and GSCA databases unveiled biological processes and signaling pathways associated with PDGs. Cytohubba app was utilized to identify 6 hub genes from the PDGs. Verification of hub genes was conducted using three GEO datasets and Western blot. Histopathological staining data of hub genes in LIHC patients were retrieved from the Human Protein Atlas database. Comprehensive analyses of hub genes were performed, including immune infiltration, prognosis, survival, methylation, gene mutation, related miRNA, and single-cell type. Potential therapeutic drugs were predicted using GDSC and CTRP databases.ResultA total of 1259 differential genes were screened, yielding 82 PDGs (36 up-regulated and 46 down-regulated genes). Hub genes identified included CDC20, TOP2A, CDK1 (up-regulated), and CAT, TAT, FTCD (down-regulated). These hub genes exhibited strong associations with immune cells and showed promising prognostic value based on AUC analysis. Reduced promoter methylation levels of TOP2A, CDK1, and FTCD in LIHC were observed. Single nucleotide polymorphisms analysis highlighted prevalent variants and miRNA expression associations impacting patient survival. Hub genes were enriched in various cell types. Trametinib, selumetinib, RDEA119, and teniposide were identified as potential drugs for LIHC treatment.ConclusionCDC20, TOP2A, CDK1, CAT, TAT, and FTCD may contribute to LIHC development and serve as novel prognostic biomarkers.

2025-01-01·Cancer Treatment and Research Communications

Targeting the phosphatidylinositol-3-kinase (PI3K) and mitogen activated protein kinase (MAPK) signalling pathways to enhance chemoradiotherapy in locally advanced rectal cancer

Article

作者: Hennessy, Bryan T ; Coulter, Jonathan A ; Grogan, Liam ; McNamara, Deborah A ; Workman, Julie ; Farrelly, Angela ; Breathnach, Oscar ; Bennie, Lindsey ; Toomey, Sinead ; Carr, Aoife ; Eustace, Alex J ; Fay, Joanna ; O'Neill, Brian D P ; Cremona, Mattia ; Morris, Patrick G

Responses to neoadjuvant chemoradiotherapy for locally advanced rectal cancer are not uniform. The phosphatidylinositol-3 kinase (PI3K) and mitogen-activated protein kinase (MAPK) pathways are involved in tumorigenesis and treatment resistance in many cancers; therefore, targeting these pathways could enhance response to chemoradiotherapy. A panel of colorectal cancer (CRC) cell lines (n = 10) with varying PI3K and MAPK mutational backgrounds were treated with combinations of 5-Flourouracil (5-FU), radiation, the PI3K inhibitor copanlisib, and/or the MEK inhibitor refametinib, and their effects on proliferation in vitro were measured. BALB/c SCID mice were implanted with CRC cell lines representative of each mutational background, treated with copanlisib and/or chemoradiotherapy, and monitored for tumor growth. In vitro, PIK3CA mutated cell lines were most sensitive to copanlisib (IC50=28 nM) and KRAS mutated cell lines were most sensitive to refametinib (IC50 = 36 nM), while the combination of copanlisib and refametinib was synergistic in 9/10 cell lines tested. The addition of copanlisib to 5-FU chemoradiotherapy inhibited cell growth compared to 5-FU chemoradiotherapy alone, an effect that was most notable in LS-1034 (KRAS mutated) and Caco-2 (PIK3CA/KRAS wild-type) cell lines. In vivo copanlisib and 5-FU chemoradiotherapy reduced tumor growth in all xenograft models and increased overall survival in LS-1034 and Caco-2 xenografts. Our results suggest that activation of the kinase signalling pathway may modulate PI3K/MEK inhibitor responsiveness in colorectal cancer. Furthermore, the addition of copanlisib to 5-FU chemoradiotherapy resulted in an enhanced anti-proliferative cytotoxic effect compared to 5-FU chemoradiotherapy alone, regardless of the background mutational status, and supports further clinical development of this regimen.

2025-01-01·Gene

Immune-related glycosylation genes based classification predicts prognosis and therapy options of osteosarcoma

Article

作者: Wang, Wen ; Jiao, Yunjia ; Du, Xiaojing ; Ye, Zhaoming

Osteosarcoma is the most common primary bone malignancy, with a very poor prognosis. Aberrant glycosylation is close involvement in osteosarcoma. Accordingly, this study aimed at investigating the role of glycosylation genes in the prognosis and therapy options of osteosarcoma. The microenvironment of osteosarcoma was assessed using estimate algorithm. A total of 20 immune-related glycosylation genes (IRGGs) was identified using Pearson correlation analysis. Accordingly, osteosarcoma patients were divided into C1 and C2 type using consensus clustering. Multiple algorithms (Xcell, MCP-counter, ssGSEA, epic, quantiseq), cancer immune cycle analysis, and GSVA were applied to estimate the immune, molecule and metabolism characteristics of osteosarcoma, indicating that C1 type was featured with high immune infiltration, high glycosylation, enriched MEK signaling, and good prognosis, while C2 type was characterized by more metastasis, enriched immunotherapy-positive gene signatures, high tumor mutation burden, and poor prognosis. Results from TIDE algorithm and immunotherapy datasets suggested the C2 type's preference of immune checkpoint inhibitors (ICIs), while data of GDSC, CMap analysis and cell experiments indicated that C1 type was sensitivity to MEK inhibitor PD0325901. In addition, univariate Cox and Lasso analysis was combined to establish an IRGGs' risk score containing 6 genes (B3GNT8, FUT7, GAL3ST4, GALNT14, HS3ST2, and MFNG). The data of DCA and ROC indicated its well prediction of prognosis in osteosarcoma. Finally, cellular location analysis showed that the 6 genes not only distributed in tumor cells but also in immune cells. In summary, the classification and risk score based on IRGGs effectively predicted the prognosis and therapy options of osteosarcoma. Further studies on IRGGs may contribute to the understanding of cancer immunity in osteosarcoma.

100 项与 Refametinib 相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
-	-	-	DB06309

研发状态

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
转移性胰腺癌	临床2期	美国	Bayer AG	2011-01-01
转移性胰腺癌	临床2期	法国	Bayer AG	2011-01-01
转移性胰腺癌	临床2期	比利时	Bayer AG	2011-01-01
转移性胰腺癌	临床2期	英国	Bayer AG	2011-01-01
肝细胞癌	临床2期	新加坡	Bayer AG	2010-12-01
肝细胞癌	临床2期	中国香港	Bayer AG	2010-12-01
肝细胞癌	临床2期	韩国	Bayer AG	2010-12-01
肝细胞癌	临床2期	中国台湾	Bayer AG	2010-12-01
晚期癌症	临床2期	美国	Bayer AG	2008-11-01
晚期癌症	临床2期	加拿大	Bayer AG	2008-11-01

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临床结果

适应症

分期

评价

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT01392521 (Pubmed \| Target Oncol) 人工标引	临床1期	晚期癌症	64	Copanlisib+Refametinib	(鬱窪築淵衊糧繭廠鑰鹽) = copanlisib 0.4 mg/kg weekly and refametinib 30 mg twice daily 顧齋選製繭積範簾鏇窪 (膚淵積獵願遞構願構膚 ) 更多	积极	2020-04-01
NCT01251640 (Pubmed \| Target Oncol) 人工标引	临床1/2期	胰腺癌	90	Gemcitabine+Refametinib	(蓋鑰範襯範衊網糧襯齋) = 膚顧餘選鑰積夢顧餘鑰築淵獵膚觸鏇夢網壓製 (選壓襯蓋簾窪鏇壓淵觸 ) 更多	积极	2017-02-01
NCT01251640 (AACR2015)	临床1/2期	不能切除性胰腺癌	69	refametin (KRAS wild-type)	(鑰窪鏇蓋遞鏇範蓋窪觸) = 齋窪淵襯積憲觸製夢觸膚獵繭壓構觸選網淵衊 (艱簾壓窪鏇製憲選衊蓋 ) 更多	-	2015-08-01
				refametin (KRAS mutant)	(鑰窪鏇蓋遞鏇範蓋窪觸) = 製鑰餘齋鹽夢構網繭選膚獵繭壓構觸選網淵衊 (艱簾壓窪鏇製憲選衊蓋 ) 更多
NCT01251640 (ASCO2014)	临床2期	不能切除性胰腺癌	90	Refametinib + Gemcitabine	(艱窪淵遞簾繭網顧襯築) = 鏇選鑰淵壓鑰鏇製窪選觸鏇積壓鹽齋選觸簾積 (網醖壓憲襯憲壓積艱鹽 ) 更多	-	2014-05-20
NCT01251640 (ASCO2014)	临床2期	不能切除性胰腺癌	60	Refametinib + Gemcitabine	(鏇夢鹹網顧顧壓範壓範) = 顧構糧醖鹹廠夢憲繭繭衊糧夢壓網襯製憲齋糧 (積願鬱襯簾膚網壓選衊 ) 更多	-	2014-05-20
NCT01392521 (ASCO2014)	临床1期	晚期癌症	49	Copanlisib	(憲鏇艱鏇餘淵範選鑰醖) = 構膚獵餘觸網窪觸鹽餘艱艱憲製夢壓遞願夢蓋 (鹽遞夢衊遞簾鹹顧窪選 ) 更多	-	2014-05-20
				Refametinib	(憲鏇艱鏇餘淵範選鑰醖) = 積淵壓顧範餘壓範艱積艱艱憲製夢壓遞願夢蓋 (鹽遞夢衊遞簾鹹顧窪選 ) 更多
EULAR2009	N/A	关节炎	-	RDEA436	(衊鏇選遞鹽鏇遞膚顧選) = 餘膚鹽廠糧鏇構製鬱網鏇願憲衊範糧壓廠製廠 (遞構窪選夢鹹範網鹹襯 ) 更多	-	2009-06-10
				RDEA119	(蓋獵製齋衊壓壓獵廠壓) = 窪憲齋築憲襯鹽鏇積壓鏇壓壓鏇壓鏇獵膚窪製 (壓觸鏇蓋齋窪觸網鑰鬱 )
EULAR2008	N/A	关节炎	-	RDEA119	(網衊鬱繭築遞夢淵醖壓) = 窪積鏇觸齋鬱醖蓋鏇顧鬱範憲壓膚選遞齋遞構 (糧願壓繭繭遞鑰淵範願 ) 更多	-	2008-06-11
				Indomethacin	(餘鏇製鹽膚窪夢壓簾衊) = 願構鹹選獵構憲鬱襯鏇壓窪構範夢構夢願築網 (衊構膚糧鹹積膚齋鑰構 )