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概览

疾病领域	数量

肿瘤	3

排名前五的药物类型	数量

小分子化药	3
未知	2
酶	1

排名前五的靶点	数量

MTAP	1
SLITRK6(神经突触相关蛋白SLITRK6)	1
SDH2(线粒体复合体II；琥珀酸脱氢酶)	1
GLUT1 x PC	1

关联

7

项与 Metabomed Ltd. 相关的药物

ACSS2 (MetaboMed)

靶点-

作用机制-

在研机构

Metabomed Ltd.初创企业

原研机构

Metabomed Ltd.初创企业

在研适应症

肿瘤

非在研适应症-

最高研发阶段早期临床1期

首次获批国家/地区-

首次获批日期-

MTB-22252

靶点

MTAP

作用机制

MTAP inhibitors

在研机构

Metabomed Ltd.初创企业

原研机构

Metabomed Ltd.初创企业

在研适应症

肿瘤

非在研适应症-

最高研发阶段临床前

首次获批国家/地区-

首次获批日期-

PC/GluT(Metabomed)

靶点

GLUT1 x PC

作用机制

GLUT1调节剂 [+1]

在研机构

Metabomed Ltd.初创企业

原研机构

Metabomed Ltd.初创企业

在研适应症-

非在研适应症-

最高研发阶段临床前

首次获批国家/地区-

首次获批日期-

100 项与 Metabomed Ltd. 相关的临床结果

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0 项与 Metabomed Ltd. 相关的专利（医药）

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3

项与 Metabomed Ltd. 相关的文献（医药）

2021-07-01·Cancer Research

Abstract 2337: Recapitulating and targeting hypoxia-induced tumor metabolism using zebrafish tumor-derived xenografts-models

作者: Fahlgren, Anna ; Rodriguez, Gabriela Vazquez ; Ali, Zaheer ; Goutopoulos, Andreas ; Erkstam, Anna ; Vildevall, Malin ; Jensen, Lasse D.

AbstractHypoxia-induced metabolic pathways are excellent anti-tumor targets as these are specifically but broadly activated even under normoxia in cancer. However, these pathological metabolic profiles are often poorly recapitulated in vitro, and developing new drugs that target these tumor-specific metabolic enzymes therefore require in vivo models, even from an early stage. Screening of drug candidates or cell/PDX model libraries using zebrafish tumor xenograft (ZTX) models has become an attractive alternative to mice for fast assessment of drug efficacy in a variety of indications in vivo, but traditionally such models have not allowed for testing drugs that target hypoxia-induced metabolic pathways. Controlling the extent and duration of intratumor hypoxia in vivo has been done by mixing nitrogen gas directly into the water surrounding the larvae, and these systems have therefore not been amenable for high-throughput screening purposes. In order to advance the use of ZTX technologies and allow screening of drugs targeting hypoxia-induced metabolic pathways, a new, high-throughput platform for controlling hypoxia in zebrafish larvae is needed.Here we demonstrate the development of a ZTX platform in which hypoxia-induced pathophysiological changes in the tumor microenvironment are evaluated, and up-regulation of relevant drug targets are coupled to cell- and drug-screening capabilities. The system that we have developed here allows for screening of hundreds of tumor-bearing larvae in many different experimental groups at the same time, using normoxia and hypoxia in parallel. Using this innovative platform, we show that hypoxia exposure induces metastatic dissemination in a panel of 12 tumor cell lines, spanning multiple indications and that a specific drug, currently under clinical development, targeting hypoxia-induced tumor metabolism, is effective in killing tumor cells and reducing metastatic dissemination only under hypoxic conditions, thereby validating the proposed mechanism of action.In conclusion, we have developed a hypoxia-ZTX screening system that allows identification of alternate indications for approved drugs or drugs in phase II or III, expanding the possibility for on-labeled use of anti-cancer therapeutics. Specifically, we demonstrated that a novel drug candidate targeting a specific hypoxia-induced signaling pathway show high anti-tumor efficacy, reduces primary tumor burden, and inhibits metastatic dissemination. This drug would thereby be promising for expanded clinical development and on-label use.Citation Format: Gabriela Vazquez Rodriguez, Zaheer Ali, Malin Vildevall, Anna Erkstam, Andreas Goutopoulos, Anna Fahlgren, Lasse D. Jensen. Recapitulating and targeting hypoxia-induced tumor metabolism using zebrafish tumor-derived xenografts-models [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2337.

2020-08-15·Cancer Research

Abstract LB-295: Discovery of potent selective oral ACSS2 inhibitors for the treatment of acetate avid tumors

作者: Paz, Dikla ; Erez, Omri ; Oppenheimer, Hannah ; Gottlieb, Eyal ; Nakache, Philippe ; Kovalerchik, Dimitri ; Mor, Inbal ; Botti, Simone ; Pastukh, Nina ; Goutopoulos, Andreas ; Hay-Koren, Avital ; Alchanati, Iris

AbstractUnder the low oxygen and lipid-depleted conditions, often encountered in the tumor microenvironment, acetate is used as nutrient by cancer cells for the biosynthesis of fatty acids. ACSS2, the enzyme responsible for acetate capture within the cell and its conversion into Acetyl-CoA, is upregulated under metabolically stressed conditions and its silencing is shown to inhibit tumor growth in xenografts. Two independent HTS campaigns identified the same small molecule ACSS2 inhibitor series that exhibited uncompetitive binding behavior in respect to ATP. A co-crystal structure of human ACSS2 in complex with a congener of the series revealed that it binds in the acetate pocket and forms favorable interactions with ATP, which is bound adjacently. These compounds were over 1000-fold times selective for ACSS2 over the mitochondrial ACSS1 and other Acyl-CoA synthetases. Medicinal chemistry optimization of this series resulted in advanced compounds with sub-nanomolar biochemical potency and single digit nanomolar cellular EC50s in inhibiting de novo fatty acid synthesis from labeled acetate and excellent pharmacokinetic properties. In vivo, in mice, these compounds inhibited labeling of fatty acids in various tissues after administration of labelled acetate or ethanol. They exhibited in vivo anti-tumor efficacy after oral administration in xenograft models that are acetate avid, whereas had no effect in tumors that show low acetate uptake. MTB-9655, one of the compounds from this series with optimally balanced properties, is currently entering IND-enabling studies to allow its testing in cancer patients.Citation Format: Andreas Goutopoulos, Omri Erez, Philippe Nakache, Iris Alchanati, Avital Hay-Koren, Dikla Paz, Dimitri Kovalerchik, Hannah Oppenheimer, Eyal Gottlieb, Simone Botti, Inbal Mor, Nina Pastukh. Discovery of potent selective oral ACSS2 inhibitors for the treatment of acetate avid tumors [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr LB-295.

Metabolites3区 · 生物学

Secondary Metabolites of Aeromonas veronii Strain A134 Isolated from a Microcystis aeruginosa Bloom

3区 · 生物学

ArticleOA

作者: Weiss, Gad ; Kovalerchick, Dimitry ; Murik, Omer ; Carmeli, Shmuel ; Sukenik, Assaf ; Kaplan, Aaron

Aeromonas veronii strain A134 was isolated from Microcystis aeruginosa colonies collected from Lake Kinneret (Sea of Galilee), Israel. The Aeromonas culture media inhibited the growth of M. aeruginosa (strain MGK). The crude extract of a large-scale culture of A. veronii A134 was separated in a few chromatographic steps to yield three new secondary metabolites, 9-chlorolumichrome (1), veronimide (2) and veronipyrazine (3), along with a known lumichrome and several known diketopiperazines. The structures of the new compounds were established by analyses of the data from 1D and 2D NMR experiments and HRMS data of the compounds, as well as a single-crystal X-ray analysis of synthetic 1. The structure elucidation and proposed biogenesis of the new compounds are described below.

100 项与 Metabomed Ltd. 相关的药物交易

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100 项与 Metabomed Ltd. 相关的转化医学

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2024年11月05日管线快照

管线布局中药物为当前组织机构及其子机构作为药物机构进行统计，早期临床1期并入临床1期，临床1/2期并入临床2期，临床2/3期并入临床3期

药物发现

2

3

临床前

临床1期

1

其他

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当前项目

药物(靶点)	适应症	全球最高研发状态

ACSS2 (MetaboMed)	肿瘤更多	临床1期
PC/GluT(Metabomed) ( GLUT1 x PC )	-	临床前
MTB-22252 ( MTAP )	肿瘤更多	临床前
MTB-8265 ( SDH2 )	肿瘤更多	临床前
HO-1(Metabomed)	-	药物发现