This is an open-label, Phase 1, dose escalation study of oral ARQ 736 administered to subjects with advanced solid tumors harboring the mutation. The study is designed to explore the safety, tolerability, pharmacokinetics and pharmacodynamics of ARQ 736 and to define a recommended Phase 2 dose of ARQ 736.

开始日期2010-10-01

申办/合作机构-

100 项与 ARQ-736 相关的临床结果

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100 项与 ARQ-736 相关的转化医学

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100 项与 ARQ-736 相关的专利（医药）

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项与 ARQ-736 相关的文献（医药）

2016-11-04·Anti-Cancer Agents in Medicinal Chemistry4区 · 医学

Mutant B-Raf Kinase Inhibitors as Anticancer Agents

4区 · 医学

Review

作者: Bharti, Sanjay K. ; Asati, Vivek ; Mahapatra, Debarshi K.

The Ras/Raf/MEK/ERK signaling pathway involves various kinases in which each kinase is associated with one another through signals and regulates cell proliferation, differentiation and apoptosis. This pathway is dysregulated almost in all cancers due to the amplification and genetic mutation of various components of the pathway. The genetic mutations have been reported to cause drug resistance to the current chemotherapy of melanomas. B-Raf is one of the most commonly mutated proto-oncogenes and plays a significant role in the development of numerous cancers of high clinical impact. Therefore, mutant B-Raf kinase may be a promising therapeutic target for the development of novel anticancer drugs. Many BRAF inhibitors discovered during the last decade showed promising anticancer activity, especially on tumors that harbor BRAFV600E mutations. Currently, vemurafenib and dabrafenib are USFDA approved drugs used as B-Raf inhibitors. Few drugs which are under clinical development phases such as LGX818, GDC0879, XL281, ARQ736, PLX3603 (RO5212054), and RAF265 etc. pave the path for further designing of B-Raf inhibitors. The present review focuses primarily on the Ras/Raf/MEK/ERK signaling pathway with mutant B-Raf as a therapeutic target for anticancer drug development. The essential pharmacophoric features of B-Raf inhibitors, their structure activity relationships (SARs) and molecules under clinical trials have been highlighted.

2013-12-01·Journal of Hematology & Oncology1区 · 医学

B-Raf and the inhibitors: from bench to bedside

1区 · 医学

ReviewOA

作者: Michael Karsy ; Tiangui Huang ; Jian Zhuge ; Delong Liu ; Minghao Zhong

AbstractThe B-Raf protein is a key signaling molecule in the mitogen activated protein kinase (MAPK) signaling pathway and has been implicated in the pathogenesis of a variety of cancers. An important V600E mutation has been identified and can cause constitutive B-Raf activation. Recent studies have evaluated a variety of small molecule inhibitors targeting B-Raf, including PLX4032/vemurafenib, dabrafenib, LGX818, GDC0879, XL281, ARQ736, PLX3603 (RO5212054), and RAF265. Therapeutic resistance has been identified and various mechanisms described. This review also discussed the current understanding of B-Raf signaling mechanism, methods of mutation detection, treatment strategies as well as potential methods of overcoming therapeutic resistance.

2011-12-15·Clinical Cancer Research1区 · 医学

Role of BRAF in Thyroid Oncogenesis

1区 · 医学

Review

作者: Phay, John E. ; Shah, Manisha H. ; Caronia, Lisa M.

AbstractBRAF, a cytoplasmic serine–threonine protein kinase, plays a critical role in cell signaling as an activator within the mitogen-activated protein kinase (MAPK) pathway. The most common BRAF mutation is the V600E transversion, which causes constitutive kinase activity. This mutation has been found in a multitude of human cancers, including both papillary thyroid cancer (PTC) and papillary-derived anaplastic thyroid cancer (ATC), in which it initiates follicular cell transformation. With such a high frequency of BRAF mutations in PTC (44%) and PTC-derived ATC (24%), research in BRAFV600E detection for diagnostic purposes has shown high sensitivity and specificity for tumor cell presence. BRAFV600E in PTC has also provided valuable prognostic information, as its presence has been correlated with more aggressive and iodine-resistant phenotypes. Such findings have initiated research in targeting oncogenic BRAF in cancer therapeutics. Although multiple phase II clinical trials in patients with iodine-refractory metastatic PTC have shown significant efficacy for sorafenib, a first-generation BRAF inhibitor, the mechanism by which it mediates its effect remains unclear because of multiple additional kinase targets of sorafenib. Additionally, preclinical and clinical studies investigating combination therapy with agents such as selective (PLX 4032) and potent (BAY 73-4506 and ARQ 736) small-molecule BRAF inhibitors and MAP/extracellular signal-regulated kinase (ERK) kinase inhibitors (AZD6244) hold great promise in the treatment of BRAFV600E cancers and may eventually play a powerful role in changing the clinical course of PTC and ATC. Clin Cancer Res; 17(24); 7511–7. ©2011 AACR.

100 项与 ARQ-736 相关的药物交易

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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
肿瘤	临床1期	-	ArQule, Inc.	-
实体瘤	临床1期	美国	Merck GmbH	-
实体瘤	临床1期	意大利	Merck GmbH	-
晚期恶性实体瘤	药物发现	美国	-	2010-10-01
晚期恶性实体瘤	药物发现	意大利	-	2010-10-01