miridesap   Click here for help

GtoPdb Ligand ID: 8256

Synonyms: compound 52 [PMID 14998318] [8] | CPHPC | GSK2315698 | Ro 63-8695 [8]
PDB Ligand
Compound class: Synthetic organic
Comment: Miridesap (CPHPC) is reported as a chemical which depletes the glycoprotein serum amyloid P component (SAP) in mice [1] and humans [2]. 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 [8]. 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 [3]. SAP is a drug target for the treament of neurodegenerative diseases (amyloidoses) [7].
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2D Structure
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Physico-chemical Properties
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Hydrogen bond acceptors 8
Hydrogen bond donors 2
Rotatable bonds 9
Topological polar surface area 115.22
Molecular weight 340.16
XLogP -0.15
No. Lipinski's rules broken 0
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InChI InChI=1S/C16H24N2O6/c19-13(17-9-3-5-11(17)15(21)22)7-1-2-8-14(20)18-10-4-6-12(18)16(23)24/h11-12H,1-10H2,(H,21,22)(H,23,24)/t11-,12-/m1/s1
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Summary of Clinical Use Click here for help
Miridesap is used to pre-treat patients prior to treatment with the investigational anti-SAP monoclonal antibody dezamizumab [5]. Development of miridesap/dezamizumab for amyloidosis has been discontinued.
Mechanism Of Action and Pharmacodynamic Effects Click here for help
CPHPC effectively reduces circulating and visceral SAP in a mouse model of systemic AA amyloidosis (transgenics expressing human SAP) [1] and in humans [2] 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 [1]. CPHPC combined with immunotherapy using mAb dezamizumab (GSK2398852) is predicted to clear the persistent SAP in amyloid fibrils.
Clinical Trials
Clinical Trial ID Title Type Source Comment References
NCT01777243 A Study to Evaluate the Safety of GSK2398852 When Co-administered With GSK2315698 in Patients With Systemic Amyloidosis Phase 1 Interventional GlaxoSmithKline 5-6