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Dose Frequency Optimization of the Dual Amylin and Calcitonin Receptor Agonist KBP-088: Long-Lasting Improvement in Food Preference and Body Weight Loss.

May 1, 2020

J Pharmacol Exp Ther

Abstract Dual amylin and calcitonin receptor agonists (DACRAs) are novel candidates for treatment of type 2 diabetes and obesity because of their beneficial effects on body weight, blood glucose, insulin sensitivity, and food preference, at least short-term. DACRAs activate the receptors for a prolonged time period, resulting in metabolic effects superior to those of amylin. […]

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The Dual Amylin and Calcitonin Receptor Agonist, KBP-066, Induces an Equally Potent Weight Loss Across a Broad Dose Range While Higher Doses May Further Improve Insulin Action.

April 1, 2020

J Pharmacol Exp Ther

Abstract Pharmacological treatment with dual amylin and calcitonin receptor agonists (DACRAs) cause significant weight loss and improvement of glucose homeostasis. In this study, the maximally efficacious dose of the novel DACRA, KeyBiosciencePeptide (KBP)-066, was investigated. Two different rat models were used: high-fat diet (HFD)-fed male Sprague-Dawley rats and male Zucker diabetic fatty (ZDF, /) rats […]

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Extracellular Matrix Fragments of the Basement Membrane and the Interstitial Matrix Are Serological Markers of Intestinal Tissue Remodeling and Disease Activity in Dextran Sulfate Sodium Colitis.

November 1, 2019

Dig Dis Sci

Abstract BACKGROUND Chronic intestinal inflammation results in tissue damage partly caused by an increase in matrix metalloproteinases (MMP) activity causing degradation of extracellular matrix (ECM) proteins. We studied intestinal tissue remodeling by quantifying ECM protein fragments in serum in dextran sulfate sodium (DSS)-induced colitis, to investigate ECM protein fragments as serological biomarkers of intestinal tissue […]

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A dual amylin and calcitonin receptor agonist inhibits pain behavior and reduces cartilage pathology in an osteoarthritis rat model.

September 1, 2019

Osteoarthritis Cartilage

Abstract OBJECTIVES Pain and disability are the main clinical manifestations of osteoarthritis, for which only symptomatic therapies are available. Hence, there is a need for therapies that can simultaneously alter disease progression and provide pain relief. KBP is a dual amylin- and calcitonin-receptor agonist with antiresorptive and chondroprotective properties. In this study we investigated the […]

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A non-invasive biomarker of type III collagen degradation reflects ischaemia reperfusion injury in rats.

August 1, 2019

Nephrol Dial Transplant

Abstract BACKGROUND Maintenance of kidney function in kidney allografts remains a challenge, as the allograft often progressively develops fibrosis after kidney transplantation. Fibrosis is caused by the accumulation of extracellular matrix proteins like type I and III collagen (COL I and III) that replace the functional tissue. We assessed the concentrations of a neo-epitope fragment […]

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The Dual Amylin and Calcitonin Receptor Agonist KBP-088 Induces Weight Loss and Improves Insulin Sensitivity Superior to Chronic Amylin Therapy.

July 1, 2019

J Pharmacol Exp Ther

Abstract KBP-088 (KeyBiosciencePeptide 088) is a potent dual amylin and calcitonin receptor agonist (DACRA). DACRAs are known to elicit potent activity in terms of typical amylin-induced responses, such as reducing food intake and body weight. However, to what extent amylin infusion can mimic the effects of the dual agonist KBP-088 is unknown. We studied the […]

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Biochemical and histological characterisation of an experimental rodent model of non-alcoholic steatohepatitis – Effects of a peroxisome proliferator-activated receptor gamma (PPAR-γ) agonist and a glucagon-like peptide-1 analogue.

March 1, 2019

Biomed Pharmacother

Abstract BACKGROUND Non-alcoholic steatohepatitis (NASH) is a prevalent disease that is highly associated with the metabolic syndrome and type II diabetes. The development of in vivo models that reflect all nuances of the human NASH pathology is essential for drug discovery and development. We aimed to further characterise a dietary induced model of NASH both […]

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GPDPLQ(1237)-A Type II Collagen Neo-Epitope Biomarker of Osteoclast- and Inflammation-Derived Cartilage Degradation in vitro.

February 28, 2019

Sci Rep

Abstract C-telopeptide of type II collagen (CTX-II) has been shown to be a highly relevant biomarker of cartilage degradation in human rheumatic diseases, if measured in synovial fluid or urine. However, serum or plasma CTX-II have not been demonstrated to have any clinical utility to date. Here, we describe the GPDPLQ ELISA which targets the […]

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Optimization of tolerability and efficacy of the novel dual amylin and calcitonin receptor agonist KBP-089 through dose escalation and combination with a GLP-1 analog.

November 1, 2017

Am J Physiol Endocrinol Metab

Abstract Amylin and GLP-1 agonism induce a well-known anorexic effect at dose initiation, which is managed by dose escalation. In this study we investigated how to optimize tolerability while maintaining efficacy of a novel, highly potent dual amylin and calcitonin receptor agonist (DACRA), KBP-089. Furthermore, we tested the GLP-1 add-on potential of KBP-089 in high-fat […]

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The Dual Amylin- and Calcitonin-Receptor Agonist KBP-042 Works as Adjunct to Metformin on Fasting Hyperglycemia and HbA1c in a Rat Model of Type 2 Diabetes.

July 1, 2017

J Pharmacol Exp Ther

Abstract KBP-042 is a dual amylin and calcitonin receptor agonist that increases glucose tolerance and insulin action and reduces body weight in rat models of obesity and prediabetes. The objective of the present study was to 1) evaluate KBP-042 as a treatment of late-stage type 2 diabetes in a rat model and 2) assess the […]

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