伐他拉尼(Vatalanib succinate) - 药物靶点：PDGFR x VEGFR1 x VEGFR2 x VEGFR3 x c-Kit_专利_临床

概要

基本信息

药物类型

小分子化药

别名

PTK/ZK、Vatalanib、vatalanib-succinate

+ [7]

靶点

PDGFR x VEGFR1 x VEGFR2 x VEGFR3 x c-Kit

作用机制

PDGFR抑制剂(血小板衍生生长因子受体抑制剂)、VEGFR1拮抗剂(血管内皮细胞生长因子受体1拮抗剂)、VEGFR2拮抗剂(血管内皮细胞生长因子受体2拮抗剂)

治疗领域

肿瘤消化系统疾病免疫系统疾病+ [11]

在研适应症-

非在研适应症

晚期乳腺癌晚期癌症晚期恶性实体瘤+ [54]

原研机构

Novartis Pharma AG

在研机构-

非在研机构

Novartis AG

Dana-Farber Cancer Institute, Inc.

Novartis Pharmaceuticals Corp.

+ [3]

最高研发阶段终止临床3期

首次获批日期-

最高研发阶段(中国)-

特殊审评-

结构

分子式C24H21ClN4O4

InChIKeyLLDWLPRYLVPDTG-UHFFFAOYSA-N

CAS号212142-18-2

关联

33

项与伐他拉尼相关的临床试验

EUCTR2006-004824-35-IT / Not yet recruitingN/A

A double-blind, randomized phase II study of once daily versus twice daily PTK787/ZK 222584 treatment in patients with advanced, previously treated metastatic adenocarcinoma of the colon or rectum - ND

开始日期2007-03-29

申办/合作机构

Schering AG

NCT00390000 / Completed临床1期

Phase I Study of PTK/ZK in Combination With Pemetrexed Disodium (ALIMTA)

RATIONALE: Vatalanib and pemetrexed disodium may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Vatalanib may also stop the growth of tumor cells by blocking blood flow to the tumor. Giving vatalanib together with pemetrexed disodium may kill more tumor cells.
PURPOSE: This phase I trial is studying the side effects and best dose of vatalanib when given together with pemetrexed disodium in treating patients with advanced solid tumors.

开始日期2007-01-25

申办/合作机构

Mayo Clinic

[+1]

NCT00615160 / Terminated临床1/2期IIT

Phase II Randomized, Parallel-Group Trial on PTK-ZK With or Without DTIC in Patients With Non-resectable Metastatic Malignant Melanoma

To evaluate the efficacy of PTK-ZK on metastatic melanoma either as a single agent treatment or in combination with standard chemotherapy according to RECIST criteria. Further to evaluate the safety and tolerability of PTK-ZK in patients with metastatic melanoma either as a single agent treatment or in combination with standard chemotherapy

开始日期2006-12-01

申办/合作机构-

100 项与伐他拉尼相关的临床结果

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100 项与伐他拉尼相关的转化医学

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100 项与伐他拉尼相关的专利（医药）

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536

项与伐他拉尼相关的文献（医药）

2024-03-01·Bioactive materials

Reactive oxygen species (ROS)-mediated M1 macrophage-dependent nanomedicine remodels inflammatory microenvironment for osteoarthritis recession

Article

作者: Yi, Nanxing ; Wang, Kaiqiang ; Zhang, Weian ; Tian, Jia ; Liang, Qianqian ; Xu, Hao ; Li, Xiaofeng ; Sun, Dawei ; Xiong, Mengting ; Liu, Yang ; Wang, Yongjun ; Xue, Chunchun ; Cui, Zepeng

Osteoarthritis (OA) is a common chronic inflammatory disorder. Effective remodeling of inflammatory microenvironment in the joint is a promising strategy to prevent OA. However, current drugs remain unsatisfactory due to a lack of targeted and effective ways for relieving inflammatory conditions in OA joints. Bortezomib (BTZ), a proteasome inhibitor, could effectively inhibit proinflammatory cytokines but with poor accumulation in the inflammatory tissues. To overcome the shortcomings of BTZ delivery and to improve the efficacy of OA therapy, herein, we designed a novel nanomedicine (denoted as BTZ@PTK) by the co-assembly of BTZ and an amphiphilic copolymer (denoted as PTK) with ROS-cleaved thioketal (TK) linkages. The TK units in BTZ@PTK are first cleaved by the excessive ROS at OA sites, and then triggered the controlled release of BTZ, resulting in the accurate delivery and the inflammatory microenvironment remodeling. Accordingly, BTZ@PTK suppressed ROS generation and proinflammatory cytokines while promoting M1 macrophage apoptosis in lipopolysaccharide (LPS)-activated RAW264.7 macrophages or LPS/IFN-γ-treated primary macrophages, which leads to a better effect than BTZ. In OA mice, BTZ@PTK passively accumulates into inflamed joints to attenuate pain sensitivity and gait abnormality. Importantly, BTZ@PTK treatment successfully ameliorates synovitis with the reduction of synovial hyperplasia and synovitis scores by suppressing M1 macrophage polarization and promoting M1 macrophage apoptosis in the synovium, thereby delaying cartilage damage. Collectively, BTZ@PTK can effectively modulate inflammatory microenvironment for OA recession by activating M1 macrophage apoptosis and inhibiting M1macrophage-mediated inflammatory response.

2024-02-01·Archives of toxicology

Analysis of vascular disruption in zebrafish embryos as an endpoint to predict developmental toxicity

Article

作者: Tal, Tamara ; Nöth, Julia ; Ambekar, Akhil ; Scholz, Stefan ; Kießling, Tobias R ; Lai, Chih ; Busch, Wibke

Abstract:

Inhibition of angiogenesis is an important mode of action for the teratogenic effect of chemicals and drugs. There is a gap in the availability of simple, experimental screening models for the detection of angiogenesis inhibition. The zebrafish embryo represents an alternative test system which offers the complexity of developmental differentiation of an entire organism while allowing for small-scale and high-throughput screening. Here we present a novel automated imaging-based method to detect the inhibition of angiogenesis in early life stage zebrafish. Video subtraction was used to identify the location and number of functional intersegmental vessels according to the detection of moving blood cells. By exposing embryos to multiple tyrosine kinase inhibitors including SU4312, SU5416, Sorafenib, or PTK787, we confirmed that this method can detect concentration-dependent inhibition of angiogenesis. Parallel assessment of arterial and venal aorta ruled out a potential bias by impaired heart or blood cell development. In contrast, the histone deacetylase inhibitor valproic acid did not affect ISV formation supporting the specificity of the angiogenic effects. The new test method showed higher sensitivity, i.e. lower effect concentrations, relative to a fluorescent reporter gene strain (Tg(KDR:EGFP)) exposed to the same tyrosine kinase inhibitors indicating that functional effects due to altered tubulogenesis or blood transport can be detected before structural changes of the endothelium are visible by fluorescence imaging. Comparison of exposure windows indicated higher specificity for angiogenesis when exposure started at later embryonic stages (24 h post-fertilization). One of the test compounds was showing particularly high specificity for angiogenesis effects (SU4312) and was, therefore, suggested as a model compound for the identification of molecular markers of angiogenic disruption. Our findings establish video imaging in wild-type strains as viable, non-invasive, high-throughput method for the detection of chemical-induced angiogenic disruption in zebrafish embryos.

2023-10-01·Journal of ethnopharmacology

Xinkeshu tablets promote angiogenesis in zebrafish embryos and human umbilical vein endothelial cells through multiple signaling pathways

Article

作者: Zhang, Yun ; He, Qiuxia ; Zhang, Huazheng ; Xia, Qing ; Liu, Kechun ; Liu, Qing ; Zhou, Honglei ; An, Ying

ETHNOPHARMACOLOGICAL RELEVANCE:

Angiogenesis is particularly important in ischemic cardiovascular diseases such as coronary heart disease (CHD). Xinkeshu tablets (XKS) are a commonly used Chinese patent medicine for CHD with a defined clinical effect. However, the proangiogenic effect of XKS remains unknown.

AIM OF THE STUDY:

We attempted to investigate the chemical composition and proangiogenic effect of XKS, as well as its underlying mechanisms.

MATERIALS AND METHODS:

The chemical composition of a XKS methanol extract was analyzed using a UPLC-Q-Orbitrap-MS system. The compound's proangiogenic effects were evaluated in zebrafish embryos and human umbilical vein endothelial cells (HUVECs). Furthermore, the underlying mechanisms were investigated using transcriptome assays and real-time quantitative PCR validation.

RESULTS:

We identified 116 chemical constituents of XKS. XKS significantly stimulated subintestinal vessel plexus (SIVs) growth and rescued tyrosine kinase inhibitor (PTK787)-induced intersegmental vessels (ISVs) injury in zebrafish in a concentration-dependent manner. XKS significantly rescued the proliferation, migration capacity and tube formation of Recombinant VEGFR tyrosine kinase inhibitor II (VRI)-injured HUVECs. XKS promoted angiogenesis through multiple signaling pathways, including metabolic pathways, the PPAR signaling pathway, the AGE-RAGE signaling pathway, the NOD-like receptor signaling pathway, the VEGF signaling pathway, and the PI3K/Akt signaling pathway.

CONCLUSION:

Herein, we identified 116 chemical constituents of XKS for the first time and demonstrated that XKS may regulate angiogenesis through multiple signaling pathways to treat CHD.

2

项与伐他拉尼相关的新闻（医药）

2023-08-03

·FierceBiotech

Agios looks beyond PK activators with $17.5M deal for Alnylam's siRNA blood disease program

TMPRSS6 is being developed for patients with polycythemia vera, a disease characterized by excessive production of red blood cells that can ultimately prove fatal. Agios Pharmaceuticals is basking in the “tremendous progress” of its PK activator pipeline, but that hasn’t stopped the biotech from looking for ways to freshen up its hematology portfolio courtesy of a preclinical siRNA program from Alnylam. Agios is paying $17.5 million upfront for the program with up to $130 million in development and regulatory milestones potentially to follow. In return, Agios is taking on sole responsibility for ushering the TMPRSS6 program through the clinic and, hopefully, to market, with Alnylam providing manufacturing support for phase 1 only. The program is being developed for patients with polycythemia vera, a disease characterized by excessive production of red blood cells that can ultimately prove fatal. Despite affecting around 100,000 patients in the U.S., according to Agios, there are no disease-modifying treatments available. The aim of the siRNA program is to target knockdown of TMPRSS6, which is a key driver of red blood cell production. So far, the program has demonstrated a 90% knockdown of TMPRSS6 mRNA over three months in nonhuman primates, which Agios said supports “the potential for an infrequent dosing regimen.” “This program is highly aligned with our core scientific expertise, clinical development and commercial capabilities in rare hematology as well as our business development strategy to expand beyond our industry-leading pipeline of PK activators,” Agios CEO Brian Goff said in the release. “We look forward to initiating IND-enabling studies this year with the aim of delivering a transformative treatment option for this patient community with profound unmet need.” Agios describes itself as the “pioneering leader in PK activation.” In the company’s second-quarter earnings release, which coincided with the licensing announcement, Goff pointed to positive phase 2 data from the biotech’s approved PTK inhibitor Pyrukynd in sickle cell disease last month. But rather than double down on the “tremendous progress executing across our industry-leading pipeline of PK activators,” Goff used the earnings release to announce that the company is “further expanding our portfolio beyond PK activation through focused business development.” The latest licensing deal also marks a good summer for Alnylam, which only last week pocketed $310 million from Roche in exchange for most of the rights to the midstage hypertension med zilebesiran.

引进/卖出临床2期临床1期

2023-07-15

·PRNewswire

Leiomyosarcoma Pipeline Research Report 2023: Comprehensive Insights About 10+ Companies and 10+ Pipeline Drugs - Assessment by Product Type, Stage, RoA, and Molecule Type

DUBLIN, July 14, 2023 /PRNewswire/ -- The "Leiomyosarcoma - Pipeline Insight, 2023" clinical trials has been added to ResearchAndMarkets.com's offering. "Leiomyosarcoma - Pipeline Insight, 2023" report provides comprehensive insights about 10+ companies and 10+ pipeline drugs It covers the pipeline drug profiles, including clinical and nonclinical stage products. It also covers the therapeutics assessment by product type, stage, route of administration, and molecule type. It further highlights the inactive pipeline products in this space. The companies and academics are working to assess challenges and seek opportunities that could influence Leiomyosarcoma R&D. The therapies under development are focused on novel approaches to treat/improve Leiomyosarcoma. Leiomyosarcoma Emerging Drugs Chapters This segment of the Leiomyosarcoma report encloses its detailed analysis of various drugs in different stages of clinical development, including phase II, I, preclinical and Discovery. It also helps to understand clinical trial details, expressive pharmacological action, agreements and collaborations, and the latest news and press releases. Leiomyosarcoma: Pipeline Development Activities The report provides insights into different therapeutic candidates in phase II, I, preclinical and discovery stage. It also analyses Leiomyosarcoma therapeutic drugs key players involved in developing key drugs. Pipeline Development Activities The report covers the detailed information of collaborations, acquisition and merger, licensing along with a thorough therapeutic assessment of emerging Leiomyosarcoma drugs. Leiomyosarcoma Emerging Drugs ADI PEG20: Polaris Group ADI-PEG 20 is a first-in-class therapeutic approach to deplete arginine and starve cancer cells. Because arginine is one of the 20 amino acids that are essential for protein synthesis and survival of cells, some cancer cells become dependent upon the external supply of arginine to survive and grow. ADI-PEG 20 is designed to deplete the external supply of arginine, which causes arginine-dependent cancer cells to die while leaving the patient's normal cells unharmed. Currently, it is in Phase III stage of clinical trial evaluation to treat Leiomyosarcoma. AL-3818: Advenchen Laboratories AL3818 is a novel small molecule PTK inhibitor being developed by Advenchen Laboratories. Advenchen Laboratories is conducting a Phase III study to evaluate the safety and efficacy of AL3818 (anlotinib) hydrochloride in the treatment of metastatic or advanced alveolar soft part sarcoma (ASPS), leiomyosarcoma (LMS), and synovial sarcoma (SS). Leiomyosarcoma: Therapeutic Assessment This segment of the report provides insights about the different Leiomyosarcoma drugs segregated based on following parameters that define the scope of the report, such as: Phases Late stage products (Phase III) Mid-stage products (Phase II) Early-stage product (Phase I) along with the details of Pre-clinical and Discovery stage candidates Discontinued & Inactive candidates Route of Administration Products have been categorized under various ROAs such as Oral Parenteral intravenous Subcutaneous Topical. Molecule Type Products have been categorized under various Molecule types such as Monoclonal Antibody Peptides Polymer Small molecule Gene therapy Product Type Leiomyosarcoma Report Assessment Pipeline Product Profiles Therapeutic Assessment Pipeline Assessment Inactive drugs assessment Unmet Needs Key Players Merck Advenchen Laboratories Trillium Therapeutics PTC Therapeutics PharmaMar Philogen EMD Serono Incyte Corporation Clovis Oncology, Inc. Key Products Avelumab AL3818 Pembrolizumab TTI-621 PTC596 ET-743 L19-hTNF M6620 Itacitinib Rucaparib For more information about this clinical trials report visit About ResearchAndMarkets.com ResearchAndMarkets.com is the world's leading source for international market research reports and market data. We provide you with the latest data on international and regional markets, key industries, the top companies, new products and the latest trends. Media Contact: Research and Markets Laura Wood, Senior Manager [email protected] For E.S.T Office Hours Call +1-917-300-0470 For U.S./CAN Toll Free Call +1-800-526-8630 For GMT Office Hours Call +353-1-416-8900 U.S. Fax: 646-607-1907 Fax (outside U.S.): +353-1-481-1716 Logo: SOURCE Research and Markets

临床3期临床2期临床1期基因疗法

100 项与伐他拉尼相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
-	-	-	DB04879

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
结肠转移性腺癌	临床3期	美国	Novartis AG	2003-02-01
结肠转移性腺癌	临床3期	澳大利亚	Novartis AG	2003-02-01
结肠转移性腺癌	临床3期	比利时	Novartis AG	2003-02-01
结肠转移性腺癌	临床3期	巴西	Novartis AG	2003-02-01
结肠转移性腺癌	临床3期	加拿大	Novartis AG	2003-02-01
结肠转移性腺癌	临床3期	捷克	Novartis AG	2003-02-01
结肠转移性腺癌	临床3期	法国	Novartis AG	2003-02-01
结肠转移性腺癌	临床3期	德国	Novartis AG	2003-02-01
结肠转移性腺癌	临床3期	匈牙利	Novartis AG	2003-02-01
结肠转移性腺癌	临床3期	意大利	Novartis AG	2003-02-01

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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


NCT00348790 (CTgov)	临床2期	肉瘤 \| 脑膜瘤	25	vatalanib	鑰憲壓鏇願遞繭夢齋觸(築鹹膚壓鏇襯膚糧夢繭) = 蓋壓範鹹觸艱積膚襯簾鑰構膚製構鬱鏇鹹鹽鬱 (簾膚窪顧廠淵繭齋獵淵, 遞繭襯鑰醖鹹繭衊淵鑰 ~ 鬱獵構積製築蓋獵窪鹽) 更多	-	2014-10-27
NCT00185588 (CTgov)	临床1/2期	胰腺癌	33	gemcitabine+Vatalanib (Stage 1 Dose Exploration 0 - Gemcitabine 700 + Vatalanib 1250)	製獵繭壓範鏇蓋壓糧餘(願廠鹹願廠範夢鏇壓觸) = 製鏇壓憲顧鑰觸顧願鹹網觸顧製鏇願積願選醖 (衊鏇顧繭夢積鑰窪襯顧, 淵夢窪鏇積積簾築鹽鹽 ~ 鏇淵廠膚糧廠窪選鏇鬱) 更多	-	2014-09-15
NCT00185588 (CTgov)	临床1/2期	胰腺癌	33	gemcitabine+Vatalanib (Stage 1 Dose Exploration 1 - Gemcitabine 850 + Vatalanib 1250)	製獵繭壓範鏇蓋壓糧餘(願廠鹹願廠範夢鏇壓觸) = 網遞膚遞窪願鬱遞鏇獵網觸顧製鏇願積願選醖 (衊鏇顧繭夢積鑰窪襯顧, 鏇壓獵窪淵積壓積顧觸 ~ 築鏇鹽鏇範遞衊願鏇獵) 更多	-	2014-09-15
NCT00072475 (CTgov)	临床2期	骨髓增生异常/骨髓增生性疾病 \| 白血病 \| 骨髓增生异常综合征	155	vatalanib	壓糧鏇鑰積淵壓觸鬱網(構顧觸蓋遞繭鹽膚製選) = 鏇獵鑰構鹹膚顧餘廠顧繭願壓築鏇淵築繭觸鏇 (範鏇築壓鹽淵廠壓鬱衊, 衊鏇觸襯蓋淵積齋衊製 ~ 構窪鬱衊範獵壓遞膚艱) 更多	-	2014-06-24
NCT00072475 (Alliance, Pubmed \| Invest New Drugs)	临床2期	骨髓增生异常综合征	155	Vatalanib 1250 mg	遞膚鹽廠遞窪觸齋鹹蓋(繭餘製膚鑰糧衊簾憲顧) = possibly related to vatalanib 獵選窪蓋壓鹽膚鑰艱遞 (醖鑰網壓構繭顧鹹醖築 ) 更多	-	2013-10-01
NCT00072475 (Alliance, Pubmed \| Invest New Drugs)	临床2期	骨髓增生异常综合征	155	Vatalanib 750-1250 mg		-	2013-10-01
NCT00053885 (CALGB 30107, Pubmed \| Lung Cancer)	临床2期	恶性间皮瘤	47	Vatalanib 1250 mg	鏇獵夢憲蓋蓋膚淵繭醖(廠繭築構構製醖夢窪衊) = 繭壓夢夢淵齋齋選顧襯積範憲遞醖壓築壓選獵 (簾選遞糧製醖觸廠鹽網 ) 更多	不佳	2012-06-01
NCT00160043 (Pubmed \| Ann Oncol)	临床2期	非小细胞肺癌二线	112	Vatalanib once-daily dosing (QD)	鑰鹽獵餘衊積襯鏇廠製(願鹹範衊構鹹齋窪鬱鏇) = 蓋築鏇鑰製遞築顧製鏇繭遞醖鹽構獵襯廠構積 (選餘壓選遞艱餘範蓋艱 ) 更多	-	2012-03-01
NCT00160043 (Pubmed \| Ann Oncol)	临床2期	非小细胞肺癌二线	112	Vatalanib two divided daily dosing (TDD)	鑰鹽獵餘衊積襯鏇廠製(願鹹範衊構鹹齋窪鬱鏇) = 窪鹹願餘廠齋遞醖積選繭遞醖鹽構獵襯廠構積 (選餘壓選遞艱餘範蓋艱 ) 更多	-	2012-03-01
ASCO2011	临床2期	复发性间变性（恶性）脑膜瘤	21	PTK787/ZK 222584	鑰衊夢憲網觸夢餘簾窪(製齋獵醖鹽夢製膚壓淵) = 製鹽製鏇鑰醖醖夢襯廠鏇醖觸願齋襯鑰鹹遞憲 (鹹壓鏇壓觸築積壓廠遞 )	-	2011-05-20
NCT00563823 (Pubmed \| Eur J Cancer)	临床2期	转移性黑色素瘤	-	Vatalanib	窪廠淵襯鬱糧網選製製(鹽簾蓋鏇遞蓋製網夢顧) = 鬱糧蓋願鹽構網願艱夢艱夢艱蓋蓋蓋壓夢構選 (鑰鹽築衊糧壓艱窪憲醖 ) 更多	不佳	2010-10-01
NCT00387933 (Pubmed \| Cancer)	临床1期	胶质瘤	37	Vatalanib	遞淵鑰獵糧憲蓋窪憲蓋(觸糧網網範廠壓範願鹽) = DLTs were hematologic, gastrointestinal, renal, and hepatic 衊齋廠窪繭憲壓齋窪鹽 (網鑰繭糧齋餘蓋齋鹹願 )	-	2009-05-15
ASCO2008	临床2期	转移性黑色素瘤	34	PTK787	鏇淵鬱艱獵鏇餘願齋糧(鬱獵壓餘獵製簾製窪築) = 願膚獵憲鏇範憲遞糧製糧顧積艱顧遞簾顧構鑰 (鹹遞簾鏇鬱衊積衊夢廠 )	-	2008-05-20