CCX832 / GSK, Amgen - LARVOL DELTA

Vascular Chemerin from PVAT contributes to Norepinephrine and Serotonin-Induced Vasoconstriction and Vascular Stiffness in a Sex-Dependent Manner. (PubMed, Am J Physiol Heart Circ Physiol) - "Chemerin1 antagonism via selective inhibitor CCX832 reduced maximal contraction to norepinephrine (NE) and serotonin (5-HT), but not angiotensin II, in isolated thoracic aorta (PVAT intact) from male Dahl SS rat...Aortic PVAT from females expressed less chemerin protein than males, suggesting PVAT as the primary source of active chemerin. We show that chemerin made by the PVAT amplifies NE and 5-HT-induced contraction and potentially induces aortic stiffening in a sex-dependent manner, highlighting the potential for chemerin to be a key factor in blood pressure control and aortic stiffening."

Journal • Cardiovascular • Hypertension • Obesity • RARRES2

Chemerin is resident to vascular tunicas and contributes to vascular tone. (PubMed, Am J Physiol Heart Circ Physiol) - "Inhibition of the receptor Chemerin1 by the receptor antagonist CCX832 resulted in loss of vascular tone that supports potential contributions of chemerin by both PVAT and the media. These data suggest that vessel-derived chemerin may support vascular tone locally through constitutive activation of Chemerin1. This posits chemerin as a potential therapeutic target in blood pressure regulation."

Journal • PLIN2 • RARRES2

Promotion of chemerin in rat diabetic kidney disease through enhancement of TGF-β1/Smads/CTGF pathway. (PubMed, Am J Transl Res) - "Chemerin may play a role in DKD by enhancing the signaling pathways of TGF-β1/Smads/CTGF transduction either in vitro or in vivo. Moreover, high glucose accelerates kidney injury by activating fibrotic pathways."

Journal • Preclinical • Diabetes • Diabetic Nephropathy • Fibrosis • Nephrology • Oncology • Renal Disease • CTGF • SMAD2 • SMAD4 • TGFB1 • TNFA

Endogenous Chemerin from PVAT Amplifies Electrical Field-Stimulated Arterial Contraction: Use of the Chemerin Knockout Rat. (PubMed, Int J Mol Sci) - "The Chemerin1 antagonist CCX832 alone inhibited EFS-induced contraction in tissues with but not without perivascular adipose tissue (PVAT)...Consistent with this finding, the magnitude of EFS-induced contraction was lower in the tissues from the KO vs. WT rats, yet the maximum response to the adrenergic stimulus PE was not different among all tissues. These studies support that endogenous chemerin modifies sympathetic nerve-mediated contraction through Chemerin1, an important finding relative in understanding chemerin's role in control of blood pressure."

Journal • Preclinical

Adipokine Chemerin Bridges Metabolic Dyslipidemia and Alveolar Bone Loss in Mice. (PubMed) - J Bone Miner Res - "The increased bone resorption activity induced by chemerin was effectively inhibited by CMKLR1 antagonist (CCX832). Antagonism of chemerin receptor also inhibited the expression of cathepsin K in the gingival tissue. Our results show that chemerin not only increases osteoclasts activity in vitro, but also that increased level of chemerin in dyslipidemic mice plays a critical role in bone homeostasis."

Journal • Biosimilar • Diabetes • Dyslipidemia • Obesity

Chemerin receptor blockade improves vascular function in diabetic obese mice via redox-sensitive- and Akt-dependent pathways. (PubMed, Am J Physiol Heart Circ Physiol) - "...Chemerin decreased insulin-induced vasodilatation in C57BL/6J mice, an effect prevented by CCX832 (ChemR23 antagonist) treatment...CCX832 also partially restored vascular insulin responses in db/db and high fat diet (HFD)-fed mice. Our novel in vivo findings highlight chemerin/ChemR23 as a promising therapeutic target to limit insulin resistance and vascular complications associated with obesity-related diabetes."

Journal • Preclinical

Resolvin E1, resolvin D1 and resolvin D2 inhibit constriction of rat thoracic aorta and human pulmonary artery induced by the thromboxane mimetic U46619. (PubMed, Br J Pharmacol) - "These data suggest that resolvins or their mimetics may prove useful novel therapeutics in diseases such as pulmonary arterial hypertension, which are characterised by increased thromboxane contractile activity."

Journal • Preclinical

Chemerin acts via CMKLR1 and GPR1 to stimulate migration and invasion of gastric cancer cells: putative role of decreased TIMP-1 and TIMP-2. (PubMed, Oncotarget) - "...These responses were inhibited by two putative receptor antagonists CCX832 and α-NETA...The data suggest a role for chemerin in promoting the invasion of gastric cancer cells via CMKLR1 and GPR1at least partly by reducing TIMP1 and TIMP2 expression. Chemerin receptor antagonists have potential in inhibiting gastric cancer progression."

Journal