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Compound class: Synthetic organic
Comment: Miridesap (CPHPC) is reported as a chemical which depletes the glycoprotein serum amyloid P component (SAP) in mice  and humans . Intellectual property for the use of CPHPC has been licensed to GlaxoSmithKline who have coded the compound GSK2315698. Structurally, CPHPC is a simplified form of a captopril dimer . Mechanistically miridesap cross-links pairs of SAP molecules in serum forming complexes that are rapidly cleared from the body and disrupts SAP binding to amyloid fibrils and neurofibrillary tangles . SAP is a drug target for the treament of neurodegenerative diseases (amyloidoses) .
Ligand Activity Visualisation Charts
These are box plot that provide a unique visualisation, summarising all the activity data for a ligand taken from ChEMBL and GtoPdb across multiple targets and species. Click on a plot to see the median, interquartile range, low and high data points. A value of zero indicates that no data are available. A separate chart is created for each target, and where possible the algorithm tries to merge ChEMBL and GtoPdb targets by matching them on name and UniProt accession, for each available species. However, please note that inconsistency in naming of targets may lead to data for the same target being reported across multiple charts.✖
|No information available.
|Summary of Clinical Use
|Miridesap is used to pre-treat patients prior to treatment with the investigational anti-SAP monoclonal antibody dezamizumab . Development of miridesap/dezamizumab for amyloidosis has been discontinued.
|Mechanism Of Action and Pharmacodynamic Effects
|CPHPC effectively reduces circulating and visceral SAP in a mouse model of systemic AA amyloidosis (transgenics expressing human SAP)  and in humans  by acting as a competitive inhibitor of SAP binding to amyloid fibrils. CPHPC-bound SAP is rapidly cleared by the liver [3-4]. Unfortunately, residual SAP bound to visceral amyloid plaques persists even with prolonged CPHPC exposure . CPHPC combined with immunotherapy using mAb dezamizumab (GSK2398852) is predicted to clear the persistent SAP in amyloid fibrils.
|Clinical Trial ID
|A Study to Evaluate the Safety of GSK2398852 When Co-administered With GSK2315698 in Patients With Systemic Amyloidosis
|Phase 1 Interventional