Delving into the Latest Updates on PROvendis GmbH with Synapse

概览

排名前五的药物类型	数量

合成多肽	1

排名前五的靶点	数量

HTRA1 x HTRA2	1

关联

2

项与 PROvendis GmbH 相关的药物

Ahp-10

靶点

HTRA1 x HTRA2

作用机制

HTRA1抑制剂 [+1]

在研机构

University of Duisburg-Essen [+1]

原研机构

University of Duisburg-Essen

在研适应症

黄斑变性 [+1]

非在研适应症-

最高研发阶段药物发现

首次获批国家/地区-

首次获批日期-

Apta-thrombin (University of Bonn)

靶点-

作用机制-

在研机构-

原研机构

PROvendis GmbH

在研适应症-

非在研适应症-

最高研发阶段无进展

首次获批国家/地区-

首次获批日期-

100 项与 PROvendis GmbH 相关的临床结果

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0 项与 PROvendis GmbH 相关的专利（医药）

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4

项与 PROvendis GmbH 相关的文献（医药）

2023-11-01·Journal of Biological Chemistry

Bispecific soluble cytokine receptor-nanobody fusions inhibit Interleukin (IL-)6 trans-signaling and IL-12/23 or tumor necrosis factor (TNF) signaling

Article

作者: Floss, Doreen M ; Werner, Julia ; Padrini, Giacomo ; Ettich, Julia ; Moll, Jens M ; Scheller, Jürgen ; Lang, Philipp A ; Wittich, Christoph ; Behnke, Kristina ; Pieper, Stephan ; Gesiorowski, Annika

At least 0.5% of people in the Western world develop inflammatory bowel disease (IBD). While antibodies that block tumor necrosis factor (TNF) α and Interleukin (IL-)23 have been approved for the treatment of IBD, IL-6 antibodies failed in the phase II clinical trial due to non-tolerable side effects. However, two clinical phase II studies suggest that inhibiting IL-6/soluble IL-6R (sIL-6R)-induced trans-signaling via the cytokine receptor gp130 benefit IBD patients with fewer adverse events. Here we develop inhibitors targeting a combination of IL-6/sIL-6R and TNF or IL-12/IL-23 signaling, named cs130-TNF^VHHFc and cs130-IL-12/23^VHHFc. Surface plasmon resonance experiments showed that recombinant cs130-TNF^VHHFc and cs130-IL-12/23^VHHFc bind with high affinity to IL-6/sIL-6R complexes and human TNFα (hTNFα) or IL-12/IL-23, respectively. Immunoprecipitation experiments have verified the higher ordered complex formation of the inhibitors with IL-6/sIL-6R and IL-12. We demonstrated that cs130-TNF^VHHFc and cs130-IL-12/23^VHHFc block IL-6/sIL-6R trans-signaling-induced proliferation and STAT3 phosphorylation of Ba/F3-gp130 cells, as well as hTNFα- or IL-23-induced signaling, respectively. In conclusion, cs130-TNF^VHHFc and cs130-IL-12/23^VHHFc represent a class of dimeric and bispecific chimeric cytokine inhibitors that consist of a soluble cytokine receptor fused to anti-cytokine nanobodies.

2023-11-01·Journal of Biological Chemistry

Respiratory syncytial virus–approved mAb Palivizumab as ligand for anti-idiotype nanobody-based synthetic cytokine receptors

Article

作者: Kolmar, Harald ; Behnke, Kristina ; Floss, Doreen M ; Wittich, Christoph ; Lang, Philipp A ; Reiners, Jens ; Moll, Jens M ; Ettich, Julia ; Scheller, Jürgen ; Christmann, Andreas ; Smits, Sander H J

Synthetic cytokine receptors can modulate cellular functions based on an artificial ligand to avoid off-target and/or unspecific effects. However, ligands that can modulate receptor activity so far have not been used clinically because of unknown toxicity and immunity against the ligands. Here, we developed a fully synthetic cytokine/cytokine receptor pair based on the antigen-binding domain of the respiratory syncytial virus-approved mAb Palivizumab as a synthetic cytokine and a set of anti-idiotype nanobodies (AIP^VHH) as synthetic receptors. Importantly, Palivizumab is neither cross-reactive with human proteins nor immunogenic. For the synthetic receptors, AIP^VHH were fused to the activating interleukin-6 cytokine receptor gp130 and the apoptosis-inducing receptor Fas. We found that the synthetic cytokine receptor AIP^VHHgp130 was efficiently activated by dimeric Palivizumab single-chain variable fragments. In summary, we created an in vitro nonimmunogenic full-synthetic cytokine/cytokine receptor pair as a proof of concept for future in vivo therapeutic strategies utilizing nonphysiological targets during immunotherapy.

2023-08-01·The Journal of biological chemistry

Synthetic receptor platform to identify loss-of-function single nucleotide variants and designed mutants in the death receptor Fas/CD95.

Article

作者: Bazgir, Farhad ; Floss, Doreen M ; Mossner, Sofie ; Scheller, Jürgen ; Rafii, Puyan ; Minafra, Anna Rita ; Moll, Jens M

Synthetic biology has emerged as a useful technology for studying cytokine signal transduction. Recently, we described fully synthetic cytokine receptors to phenocopy trimeric receptors such as the death receptor Fas/CD95. Using a nanobody as an extracellular-binding domain for mCherry fused to the natural receptor's transmembrane and intracellular domain, trimeric mCherry ligands were able to induce cell death. Among the 17,889 single nucleotide variants in the SNP database for Fas, 337 represent missense mutations that functionally remained largely uncharacterized. Here, we developed a workflow for the Fas synthetic cytokine receptor system to functionally characterize missense SNPs within the transmembrane and intracellular domain of Fas. To validate our system, we selected five functionally assigned loss-of-function (LOF) polymorphisms and included 15 additional unassigned SNPs. Moreover, based on structural data, 15 gain-of-function or LOF candidate mutations were additionally selected. All 35 nucleotide variants were functionally investigated through cellular proliferation, apoptosis and caspases 3 and 7 cleavage assays. Collectively, our results showed that 30 variants resulted in partial or complete LOF, while five lead to a gain-of-function. In conclusion, we demonstrated that synthetic cytokine receptors are a suitable tool for functional SNPs/mutations characterization in a structured workflow.

100 项与 PROvendis GmbH 相关的药物交易

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100 项与 PROvendis GmbH 相关的转化医学

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