The DARPin drug platform was established with a imaginative and prescient to develop the medical use of biologics past what was doable with monoclonal antibodies. It’s based mostly on naturally occurring ankyrin repeat domains which might be usually constructing blocks of multifunctional human proteins.
The platform permits for the era of various, well-behaved, multifunctional drug candidates. Current scientific knowledge illustrate the favorable security profile of the primary DARPin® molecules examined in sufferers. With the optimistic part III outcomes of essentially the most superior DARPin® drug candidate, abicipar, the DARPin® drug platform is doubtlessly about to realize its first advertising and marketing approval.
This assessment highlights a few of the key milestones and selections encountered when reworking the DARPin® platform from an educational idea to a biotech drug pipeline engine.
Coexisting TIF1γ-positive Main Pulmonary Lymphoepithelioma-like Carcinoma and Anti-TIF1γ Antibody-positive Dermatomyositis: A Case Report
Anti-transcriptional middleman issue 1γ (anti-TIF1γ) antibody-positive dermatomyositis (DM) is strongly related to most cancers, though the mechanism of motion continues to be unclear. We herein describe the primary recognized case of an 80-year-old lady recognized with TIF1γ-positive main pulmonary lymphoepithelioma-like carcinoma (LELC) coexisting with anti-TIF1γ antibody-positive DM.
Description: Advanced glycation endproducts (AGE) are adducts formed by the nzymatic glycation or oxidation of macromolecules. AGE forms during aging and its formation is accelerated under pathophysiologic states such as diabetes, Alzheimer’s disease, renal failure and immune/inflammatory disorders. Receptor for Advanced Glycation Endoproducts (RAGE), named for its ability to bind AGE, is a multiligand receptor belonging the immunoglobulin (Ig) superfamily. Besides AGE, RAGE binds amyloid βpeptide, S100/calgranulin family proteins, high mobility group B1 (HMGB1, also know as amphoterin) and leukocyte integrins. The human RAGE gene encodes a 404 amino acid residues (aa) type I transmembrane glycoprotein with a 22 aa signal peptide, a 320 aa extracellular domain containing an Ig-like V-type domain and two Ig like Ce-type domains, a 21 aa transmembrane domain and a 41 aa cytoplasmic domain. The V type domain and the cytoplasmic domain are important for ligand binding and for intracellular signaling, respectively. Two alternative splice variants, lacking the Vtype domain or the cytoplasmic tail, are known. RAGE is highly expressed in the embryonic central nervous system. In adult tissues, RAGE is expressed at low levels in multiple tissues including endothelial and smooth muscle cells, mononuclear phagocytes, pericytes, microglia, neurons, cardiac myocytes and hepatocytes. The expression of RAGE is upregulated upon ligand interaction. Depending on the cellular context and interacting ligand, RAGE activation can trigger differential signaling pathways that affect divergent pathways of gene expression. RAGE activation modulates varied essential cellular responses (including inflammation, immunity, proliferation, cellular adhesion and migration) that contribute to cellular dysfunction associated with chronic diseases such as diabetes, cancer, amyloidoses and immune or inflammatory disorders.
Description: A polyclonal antibody for RAGE from Human. The antibody is produced in rabbit after immunization with Human A synthesized peptide derived from human RAGE. The Antibody is tested and validated for WB, IHC, ICC/IF assays with the following recommended dilutions: WB (1:1000), IHC (1:200). This RAGE antibody is conjugated to ATTO 565.
Description: A polyclonal antibody for RAGE from Human. The antibody is produced in rabbit after immunization with Human A synthesized peptide derived from human RAGE. The Antibody is tested and validated for WB, IHC, ICC/IF assays with the following recommended dilutions: WB (1:1000), IHC (1:200). This RAGE antibody is conjugated to ATTO 633.
Description: A polyclonal antibody for RAGE from Human. The antibody is produced in rabbit after immunization with Human A synthesized peptide derived from human RAGE. The Antibody is tested and validated for WB, IHC, ICC/IF assays with the following recommended dilutions: WB (1:1000), IHC (1:200). This RAGE antibody is conjugated to ATTO 655.
Description: A polyclonal antibody for RAGE from Human. The antibody is produced in rabbit after immunization with Human A synthesized peptide derived from human RAGE. The Antibody is tested and validated for WB, IHC, ICC/IF assays with the following recommended dilutions: WB (1:1000), IHC (1:200). This RAGE antibody is conjugated to ATTO 680.
Description: A polyclonal antibody for RAGE from Human. The antibody is produced in rabbit after immunization with Human A synthesized peptide derived from human RAGE. The Antibody is tested and validated for WB, IHC, ICC/IF assays with the following recommended dilutions: WB (1:1000), IHC (1:200). This RAGE antibody is conjugated to ATTO 700.
Description: A polyclonal antibody for RAGE from Human. The antibody is produced in rabbit after immunization with Human A synthesized peptide derived from human RAGE. The Antibody is tested and validated for WB, IHC, ICC/IF assays with the following recommended dilutions: WB (1:1000), IHC (1:200). This RAGE antibody is conjugated to Alkaline Phosphatase.
Description: A polyclonal antibody for RAGE from Human. The antibody is produced in rabbit after immunization with Human A synthesized peptide derived from human RAGE. The Antibody is tested and validated for WB, IHC, ICC/IF assays with the following recommended dilutions: WB (1:1000), IHC (1:200). This RAGE antibody is conjugated to APC .
Description: A polyclonal antibody for RAGE from Human. The antibody is produced in rabbit after immunization with Human A synthesized peptide derived from human RAGE. The Antibody is tested and validated for WB, IHC, ICC/IF assays with the following recommended dilutions: WB (1:1000), IHC (1:200). This RAGE antibody is conjugated to APC/Cy7.
Description: A polyclonal antibody for RAGE from Human. The antibody is produced in rabbit after immunization with Human A synthesized peptide derived from human RAGE. The Antibody is tested and validated for WB, IHC, ICC/IF assays with the following recommended dilutions: WB (1:1000), IHC (1:200). This RAGE antibody is conjugated to Dylight 350.
Description: A polyclonal antibody for RAGE from Human. The antibody is produced in rabbit after immunization with Human A synthesized peptide derived from human RAGE. The Antibody is tested and validated for WB, IHC, ICC/IF assays with the following recommended dilutions: WB (1:1000), IHC (1:200). This RAGE antibody is conjugated to Dylight 405.
Description: A polyclonal antibody for RAGE from Human. The antibody is produced in rabbit after immunization with Human A synthesized peptide derived from human RAGE. The Antibody is tested and validated for WB, IHC, ICC/IF assays with the following recommended dilutions: WB (1:1000), IHC (1:200). This RAGE antibody is conjugated to Dylight 488.
Description: A polyclonal antibody for RAGE from Human. The antibody is produced in rabbit after immunization with Human A synthesized peptide derived from human RAGE. The Antibody is tested and validated for WB, IHC, ICC/IF assays with the following recommended dilutions: WB (1:1000), IHC (1:200). This RAGE antibody is conjugated to Dylight 594.
Description: A polyclonal antibody for RAGE from Human. The antibody is produced in rabbit after immunization with Human A synthesized peptide derived from human RAGE. The Antibody is tested and validated for WB, IHC, ICC/IF assays with the following recommended dilutions: WB (1:1000), IHC (1:200). This RAGE antibody is conjugated to Dylight 633.
Description: A polyclonal antibody for RAGE from Human. The antibody is produced in rabbit after immunization with Human A synthesized peptide derived from human RAGE. The Antibody is tested and validated for WB, IHC, ICC/IF assays with the following recommended dilutions: WB (1:1000), IHC (1:200). This RAGE antibody is conjugated to HRP.
Description: A polyclonal antibody for RAGE from Human. The antibody is produced in rabbit after immunization with Human A synthesized peptide derived from human RAGE. The Antibody is tested and validated for WB, IHC, ICC/IF assays with the following recommended dilutions: WB (1:1000), IHC (1:200). This RAGE antibody is conjugated to PE/ATTO 594.
Description: A polyclonal antibody for RAGE from Human. The antibody is produced in rabbit after immunization with Human A synthesized peptide derived from human RAGE. The Antibody is tested and validated for WB, IHC, ICC/IF assays with the following recommended dilutions: WB (1:1000), IHC (1:200). This RAGE antibody is conjugated to PerCP.
Description: A polyclonal antibody for RAGE from Human. The antibody is produced in rabbit after immunization with Human A synthesized peptide derived from human RAGE. The Antibody is tested and validated for WB, IHC, ICC/IF assays with the following recommended dilutions: WB (1:1000), IHC (1:200). This RAGE antibody is conjugated to RPE .
Description: A polyclonal antibody for RAGE from Human. The antibody is produced in rabbit after immunization with Human A synthesized peptide derived from human RAGE. The Antibody is tested and validated for WB, IHC, ICC/IF assays with the following recommended dilutions: WB (1:1000), IHC (1:200). This RAGE antibody is conjugated to Streptavidin.
Anti Human RAGE Monoclonal Antibody (Clone No. 1C5)
Description: A polyclonal antibody for RAGE from Human. The antibody is produced in rabbit after immunization with Human A synthesized peptide derived from human RAGE. The Antibody is tested and validated for WB, IHC, ICC/IF assays with the following recommended dilutions: WB (1:1000), IHC (1:200). This RAGE antibody is unconjugated.
Description: A polyclonal antibody for RAGE from Human. The antibody is produced in rabbit after immunization with Human A synthesized peptide derived from human RAGE. The Antibody is tested and validated for WB, IHC, ICC/IF assays with the following recommended dilutions: WB (1:1000), IHC (1:200). This RAGE antibody is conjugated to ATTO 390.
Description: A polyclonal antibody for RAGE from Human. The antibody is produced in rabbit after immunization with Human A synthesized peptide derived from human RAGE. The Antibody is tested and validated for WB, IHC, ICC/IF assays with the following recommended dilutions: WB (1:1000), IHC (1:200). This RAGE antibody is conjugated to ATTO 488.
Description: A polyclonal antibody for RAGE from Human. The antibody is produced in rabbit after immunization with Human A synthesized peptide derived from human RAGE. The Antibody is tested and validated for WB, IHC, ICC/IF assays with the following recommended dilutions: WB (1:1000), IHC (1:200). This RAGE antibody is conjugated to ATTO 594.
Description: A polyclonal antibody for RAGE from Human. The antibody is produced in rabbit after immunization with Human A synthesized peptide derived from human RAGE. The Antibody is tested and validated for WB, IHC, ICC/IF assays with the following recommended dilutions: WB (1:1000), IHC (1:200). This RAGE antibody is conjugated to Biotin.
Description: A polyclonal antibody for RAGE from Human. The antibody is produced in rabbit after immunization with Human A synthesized peptide derived from human RAGE. The Antibody is tested and validated for WB, IHC, ICC/IF assays with the following recommended dilutions: WB (1:1000), IHC (1:200). This RAGE antibody is conjugated to FITC.
Description: Advanced glycation endproducts (AGE) are adducts formed by the nzymatic glycation or oxidation of macromolecules. AGE forms during aging and its formation is accelerated under pathophysiologic states such as diabetes, Alzheimer’s disease, renal failure and immune/inflammatory disorders. Receptor for Advanced Glycation Endoproducts (RAGE), named for its ability to bind AGE, is a multiligand receptor belonging the immunoglobulin (Ig) superfamily. Besides AGE, RAGE binds amyloid βpeptide, S100/calgranulin family proteins, high mobility group B1 (HMGB1, also know as amphoterin) and leukocyte integrins. The mouse RAGE gene encodes a 403 amino acid (aa) residue type I transmembrane glycoprotein with a 22 aa signal peptide, a 319 aa extracellular domain containing a Ig-like V-type domain and two Ig-like Ce-type domains, a 21 aa transmembrane domain and a 41 aa cytoplasmic domain. The V type domain and the cytoplasmic domain are important for ligand binding and for intracellular signaling, respectively. Two alternative splice variants, lacking the Vtype domain or the cytoplasmic tail, are known. RAGE is highly expressed in the embryonic central nervous system. In adult tissues, RAGE is expressed at low levels in multiple tissues including endothelial and smooth muscle cells, mononuclear phagocytes, pericytes, microglia, neurons, cardiac myocytes, and hepatocytes. The expression of RAGE is upregulated upon ligand interaction. Depending on the cellular context and interacting ligand, RAGE activation can trigger differential signaling pathways that affect divergent pathways of gene expression. RAGE activation modulates varied essential cellular responses (including inflammation, immunity, proliferation, cellular adhesion, and migration) that contribute to cellular dysfunction associated with chronic diseases such as diabetes, cancer, amyloidoses, and immune or inflammatory disorders.
Description: The test principle applied in this kit is Sandwich enzyme immunoassay. The microtiter plate provided in this kit has been pre-coated with an antibody specific to Human RAGE. Standards or samples are added to the appropriate microtiter plate wells then with a biotin-conjugated antibody specific to Human RAGE. Next, Avidin conjugated to Horseradish Peroxidase (HRP) is added to each microplate well and incubated. After TMB substrate solution is added, only those wells that contain Human RAGE, biotin-conjugated antibody and enzyme-conjugated Avidin will exhibit a change in color. The enzyme-substrate reaction is terminated by the addition of sulphuric acid solution and the color change is measured spectrophotometrically at a wavelength of 450nm ± 10nm. The concentration of Human RAGE in the samples is then determined by comparing the OD of the samples to the standard curve.
Description: The test principle applied in this kit is Sandwich enzyme immunoassay. The microtiter plate provided in this kit has been pre-coated with an antibody specific to Human RAGE. Standards or samples are added to the appropriate microtiter plate wells then with a biotin-conjugated antibody specific to Human RAGE. Next, Avidin conjugated to Horseradish Peroxidase (HRP) is added to each microplate well and incubated. After TMB substrate solution is added, only those wells that contain Human RAGE, biotin-conjugated antibody and enzyme-conjugated Avidin will exhibit a change in color. The enzyme-substrate reaction is terminated by the addition of sulphuric acid solution and the color change is measured spectrophotometrically at a wavelength of 450nm ± 10nm. The concentration of Human RAGE in the samples is then determined by comparing the OD of the samples to the standard curve.
The prognosis of LELC can solely be made by a surgical lung biopsy, and never by a computed tomography-guided biopsy, due to heavy lymphocytic infiltration. This instructive case reaffirmed the significance of energetic screening for malignancy in sufferers with anti-TIF1γ antibody-positive DM.
Curiously, the outcomes additionally advised that the robust relationship which exists between anti-TIF1γ antibody-positive DM and most cancers is doubtlessly attributable to tumor-derived TIF1γ.
Worth of Space Postrema Syndrome in Differentiating Adults With AQP4 vs. MOG Antibodies
Targets: To match the frequency of space postrema syndrome (APS) in adults with anti-aquaporin-4 (AQP4) and anti-myelin oligodendrocyte glycoprotein (MOG) antibodies.
Strategies: APS is outlined as acute or subacute, single or mixed, episodic or fixed nausea, vomiting, or hiccups, persisting for not less than 48 h, which can’t be attributed to some other etiology. The presence of APS was investigated in 274 adults with AQP4 antibodies and 107 adults with MOG antibodiesfrom 10 hospitals. ‘
Outcomes: The research inhabitants comprised Korean adults (≥18 years). On the time of illness onset, 14.9% (41/274) adults with AQP4 antibodies had APS, whereas not one of the individuals with MOG antibodies developed APS (p < 0.001). Throughout the course of the illness, 17.2% (47/274) adults with AQP4 antibodies had APS in distinction to 1.9% (2/107) adults with MOG antibodies with APS (p < 0.001).
Description: Recombinant Resistin is a disulfide-linked homodimeric protein consisting of two 93 amino acid residues, and migrates as an approximately 20 kDa protein under non-reducing conditions and as a 10 kDa protein under reducing conditions in SDS-PAGE. Optimized DNA sequence encoding Human Resistin mature chain was expressed in E. coli.
Description: Recombinant Resistin is a disulfide-linked homodimeric protein consisting of two 93 amino acid residues, and migrates as an approximately 20 kDa protein under non-reducing conditions and as a 10 kDa protein under reducing conditions in SDS-PAGE. Optimized DNA sequence encoding Human Resistin mature chain was expressed in E. coli.
Conclusions: APS, one of many core scientific traits of people with AQP4 antibodies, is an especially uncommon manifestation in Korean adults with MOG antibodies.