VBY-376 / Virobay - LARVOL DELTA

Septin oligomerization regulates persistent expression of ErbB2/HER2 in gastric cancer cells. (PubMed) - Biochem J - "The FCF-induced degradation pathway is distinct from and additive with the degradation induced by inhibiting ErbB2 chaperone HSP90. These results identify septins as novel regulators of ErbB2 expression that contribute to the remarkable stabilization of the receptor at the plasma membrane of cancer cells and may provide a basis for the development of new ErbB2-targeting anti-cancer therapies."

Journal • Biosimilar • Gastric Cancer • Gastrointestinal Cancer • Oncology

Megalin/cubulin-lysosome-mediated albumin reabsorption is involved in the tubular cell activation of NLRP3 inflammasome and tubulointerstitial inflammation. (PubMed) - "Taken together, our findings suggest that megalin/cubilin and lysosome rupture are involved in albumin-triggered tubular injury and TI. This study provides novel insights into albuminuria-induced TI and implicates the active control of albuminuria as a critical strategy to halt the progression of CKD."

Journal • Biosimilar • Chronic Kidney Disease • Fibrosis • Immunology • Inflammation • Renal Disease • Systemic Sclerosis

iRGD-targeted delivery of a pro-apoptotic peptide activated by cathepsin B inhibits tumor growth and metastasis in mice. (PubMed) - Tumour Biol - "The m(KLA)-iRGD peptide inhibited tumor growth to a certain degree, resulting in a significant reduction in tumor volume (P < 0.05) and the total inhibition of metastasis at the end of the treatment. These results suggest that m(KLA)-iRGD has the potential for development as a new antitumor drug."

Journal • Biosimilar • Oncology

Evidence for a Mitochondrial Angiotensin-(1-7) System in the Kidney. (PubMed) - Am J Physiol Renal Physiol - "Lastly, immunoblot studies utilizing the Ang-(1-7)/Mas receptor antibody revealed the protein in isolated Mito from sheep renal cortex. Collectively, the current data demonstrate that Mito actively metabolize the RAS precursor protein Aogen, indicating that RAS peptides Ang II and Ang-(1-7) may be generated within Mito to establish an intra-mitochondrial RAS tone and contribute to renal mitochondrial function."

Journal • Biosimilar

IFITMs from Mycobacteria Confer Resistance to Influenza Virus When Expressed in Human Cells. (PubMed) - "As such, these bacterial proteins, when expressed alone, had diminished colocalization with cathepsin B-positive endolysosomal compartments that are the primary site of IFITM3-dependent influenza virus restriction. Though the precise evolutionary origin of vertebrate IFITMs is not known, our results support a model whereby transfer of a bacterial IFITM gene to eukaryotic cells may have provided a selective advantage against viral infection that was refined through the course of vertebrate evolution to include more robust signals for S-palmitoylation and localization to sites of endocytic virus trafficking."

Journal • Biosimilar • Immunology

Cathepsin-B-mediated cleavage of Disabled-2 regulates TGF-β-induced autophagy. (PubMed) - Nat Cell Biol - "Thus, CTSB-mediated degradation of Dab2 allows Beclin-1-Vps34 induction of autophagy, whereas sustained Dab2 expression prevents autophagy and promotes apoptosis by stabilizing the pro-apoptotic Bim protein. In vivo studies suggest that Dab2-mediated regulation of autophagy modulates chemotherapeutic resistance and tumour metastasis."

Journal • Biosimilar

A combined cheminformatic and bioinformatic approach to address the proteolytic stability challenge in peptide-based drug discovery. (PubMed) - "The key advantage of this approach is that it allows one to perform meaningful calculations with nonstandard amino acids for which little or no data exists. Finally, using both docking and molecular dynamics simulations, we examine the potential for and limitations of protease crystal structures to impact the design of proteolytically stable peptides."

Journal • Biosimilar

Angiostrongylus cantonensis cathepsin B-like protease (Ac-cathB-1) is involved in host gut penetration. (PubMed) - Parasite - "The inhibition of Ac-cathB-1 enzymatic activity with antiserum partly suppressed larval penetration ability in the isolated intestine. Thus, an effective system for heterologous expression of parasite proteases is presented for studying gene function in A. cantonensis; and Ac-cathB-1 was related to larval penetration ability in the host small intestine."

Journal • Biosimilar

Data collection strategies for time-resolved X-ray free-electron laser diffraction, and 2-color methods. (PubMed) - Struct Dyn - "Expressions are given for errors in structure factor measurement for the four approaches, and detailed simulations provided for cathepsin B and IC3 crystals. While the error is independent of the number of shots for the dose-limited goniometer method, it falls off inversely as the square root of the number of shots for the two-color and Monte Carlo methods, with a much smaller pre-factor for the two-color mode, when the first shot is below the damage threshold."

Journal • Biosimilar