Delving into the Latest Updates on Vichem Chemie Research Ltd with Synapse

概览

疾病领域	数量

肿瘤	4
感染	2
免疫系统疾病	2
血液及淋巴系统疾病	2

排名前五的药物类型	数量

小分子化药	4
化学药	1

排名前五的靶点	数量

M.tb bc1	1
CDK9(细胞周期蛋白依赖性激酶9)	1
CDK1 x CDK2 x CDK5 x CDK9 x Mcl-1	1
FLT3(酪氨酸蛋白激酶受体FLT3)	1

关联

5

项与 Vichem Chemie Research Ltd 相关的药物

VS2-370

靶点

CDK9

作用机制

CDK9抑制剂

在研机构

Vichem Chemie Research Ltd [+1]

原研机构

Vichem Chemie Research Ltd [+1]

在研适应症

HIV感染 [+1]

非在研适应症-

最高研发阶段临床1期

首次获批国家/地区-

首次获批日期-

FLT3 inhibitor (Vichem)

靶点

FLT3

作用机制

FLT3抑制剂

在研机构

Vichem Chemie Research Ltd

原研机构

Vichem Chemie Research Ltd

在研适应症

FLT3阳性急性髓性白血病

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-

AXL(Vichem)

靶点-

作用机制-

在研机构

Vichem Chemie Research Ltd

原研机构

Vichem Chemie Research Ltd

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-

100 项与 Vichem Chemie Research Ltd 相关的临床结果

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0 项与 Vichem Chemie Research Ltd 相关的专利（医药）

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38

项与 Vichem Chemie Research Ltd 相关的文献（医药）

2024-11-01·International Immunopharmacology

The role of PI3K-Akt-mTOR axis in Warburg effect and its modification by specific protein kinase inhibitors in human and rat inflammatory macrophages

Article

作者: Őrfi, László ; Hrabák, András ; Tretter, László ; Bögel, Gábor ; Murányi, József ; Sváb, Gergely ; Szokol, Bálint ; Kardon, Tamás ; Kukor, Zoltán

The Warburg effect occurs both in cancer cells and in inflammatory macrophages. The aim of our work was to demonstrate the role of PI3K-Akt-mTOR axis in the Warburg effect in HL-60 derived, rat peritoneal and human blood macrophages and to investigate the potential of selected inhibitors of this pathway to antagonize it. M1 polarization in HL-60-derived and human blood monocyte-derived macrophages was supported by the increased expression of NOS2 and inflammatory cytokines. All M1 polarized and inflammatory macrophages investigated expressed higher levels of HIF-1α and NOS2, which were reduced by selected kinase inhibitors, supporting the role of PI3K-Akt-mTOR axis. Using Seahorse XF plates, we found that in HL-60-derived and human blood-derived macrophages, glucose loading reduced oxygen consumption (OCR) and increased glycolysis (ECAR) in M1 polarization, which was antagonized by selected kinase inhibitors and by dichloroacetate. In rat peritoneal macrophages, the changes in oxidative and glycolytic metabolism were less marked and the NOS2 inhibitor decreased OCR and increased ECAR. Non-mitochondrial oxygen consumption and ROS production were likely due to NADPH oxidase, expressed in each macrophage type, independently of PI3K-Akt-mTOR axis. Our results suggest that inflammation changed the metabolism in each macrophage model, but a clear relationship between polarization and Warburg effect was confirmed only after glucose loading in HL-60 and human blood derived macrophages. The effect of kinase inhibitors on Warburg effect was variable in different cell types, whereas dichloroacetate caused a shift toward oxidative metabolism. Our findings suggest that these originally anti-cancer inhibitors may also be candidates for anti-inflammatory therapy.

2023-01-01·Molecular Immunology

Decreasing effects of protein kinase inhibitors on the expression of NOS2 and inflammatory cytokines and on phagocytosis in rat peritoneal macrophages is partly related to repolarization

Article

作者: Murányi, József ; Hrabák, András ; Kukor, Zoltán ; Szokol, Bálint ; Németh, Krisztina ; Kardon, Tamás ; Tamási, Viola ; Őrfi, László ; Bögel, Gábor

The JAK/STAT (Janus Kinase/Signal Transducer and Activator of Transcription) pathway plays a pivotal role in macrophage polarization, but other signaling routes may also be involved. The aim of this study was to reveal the relationship of activation between rat peritoneal macrophages and their polarization, to detect the signaling routes involved, and find selective protein kinase inhibitors decreasing the production of inflammatory proteins in activated peritoneal macrophages. Rat macrophages were elicited with i.p. casein injection. CD80 and CD206 markers, NOS2 (Nitric oxide synthase 2), arginase, cytokines and phagocytosis were investigated by ELISA (Enzyme Linked Immunosorbent Assay), Western Blot, fluorescent microscopic and flow cytometry. Statistical methods were ANOVA (Analysis Of Variance) and Student t-tests. Resident and elicited cells expressed both CD80 and CD206 polarization markers. The involvement of MAPK (mitogen-activated protein kinases) and JAK/STAT pathways in the polarization was evidenced by a phosphorylation array, supported by Western blotting, by cytokine markers and by the inhibitory effects of kinase inhibitors. The expression of NOS2 and inflammatory cytokines was higher in elicited cells suggesting their M1 polarization. This effect was reduced by the inhibitors of MAPK and JAK/STAT pathways. Phagocytosis was also higher in elicited macrophages and decreased by these inhibitors. Nevertheless, they cannot change macrophage polarization unambiguously, as levels of CD80 and CD206 markers were not changed. For comparison, human blood macrophages were also studied. Similar effects and several differences were observed between the two types of macrophages, suggesting the role of the previous differentiation in defining their characteristics. Selected anti-cancer protein kinase inhibitors of p38, MAPK and JAK/STAT pathways are possible candidates for the therapy of inflammatory diseases.

2021-07-01·Heliyon

Inclusion complexation of the anticancer drug pomalidomide with cyclodextrins: fast dissolution and improved solubility

Article

作者: Őrfi, László ; Dobó, Máté ; Orbán, György ; Tóth, Gergő ; Kiss, Eszter ; Horváth, Péter ; Csicsák, Dóra ; Pálla, Tamás ; Fiser, Béla ; Budai, Lívia ; Borbás, Enikő ; Kádár, Szabina ; Dobos, Judit ; Völgyi, Gergely ; Szabó, Zoltán-István

Pomalidomide (POM), a potent anticancer thalidomide analogue was characterized in terms of cyclodextrin complexation to improve its aqueous solubility and maintain its anti-angiogenic activity. The most promising cyclodextrin derivatives were selected by phase-solubility studies. From the investigated nine cyclodextrins - differing in cavity size, nature of substituents, degree of substitution and charge - the highest solubility increase was observed with sulfobutylether-β-cyclodextrin (SBE-β-CD). The inclusion complexation between POM and SBE-β-CD was further characterized with a wide variety of state-of-the-art analytical techniques, such as nuclear magnetic resonance spectroscopy (NMR), infrared spectroscopy (IR), circular dichroism spectroscopy, fluorescence spectroscopy as well as X-ray powder diffraction method (XRD). Job plot titration by NMR and the A_L-type phase-solubility diagram indicated 1:1 stoichiometry in a liquid state. Complementary analytical methods were employed for the determination of the stability constant of the complex; the advantages and disadvantages of the different approaches are also discussed. Inclusion complex formation was also assessed by molecular modelling study. Solid state complexation in a 1:1 M ratio was carried out by lyophilization and investigated by IR and XRD. The complex exhibited fast-dissolution with immediate release of POM, when compared to the pure drug at acidic and neutral pH. Kinetic analysis of POM release from lyophilized complex shows that Korsmeyer-Peppas and Weibull model described the best the dissolution kinetics. The cytotoxicity of the complex was tested against the LP-1 human myeloma cell line which revealed that supramolecular interactions did not significantly affect the anti-cancer activity of the drug. Overall, our results suggest that the inclusion complexation of POM with SBE-β-CD could be a promising approach for developing more effective POM formulations with increased solubility.

100 项与 Vichem Chemie Research Ltd 相关的药物交易

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100 项与 Vichem Chemie Research Ltd 相关的转化医学

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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

临床前

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临床1期

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当前项目

药物(靶点)	适应症	全球最高研发状态

VS2-370 ( CDK9 )	肿瘤更多	临床1期
AXL(Vichem)	肿瘤更多	临床前
Otviciclib ( CDK1 x CDK2 x CDK5 x CDK9 x Mcl-1 )	多发性骨髓瘤更多	临床前
FLT3 inhibitor (Vichem) ( FLT3 )	FLT3阳性急性髓性白血病更多	临床前
Mycobacterium Tuberculosis (Vichem) ( M.tb bc1 )	结核更多	临床前