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
1. Bodin K, Ellmerich S, Kahan MC, Tennent GA, Loesch A, Gilbertson JA, Hutchinson WL, Mangione PP, Gallimore JR, Millar DJ et al.. (2010)
Antibodies to human serum amyloid P component eliminate visceral amyloid deposits.
Nature, 468 (7320): 93-7. [PMID:20962779]
2. Gillmore JD, Tennent GA, Hutchinson WL, Gallimore JR, Lachmann HJ, Goodman HJ, Offer M, Millar DJ, Petrie A, Hawkins PN et al.. (2010)
Sustained pharmacological depletion of serum amyloid P component in patients with systemic amyloidosis.
Br J Haematol, 148 (5): 760-7. [PMID:20064157]
3. Kolstoe SE, Ridha BH, Bellotti V, Wang N, Robinson CV, Crutch SJ, Keir G, Kukkastenvehmas R, Gallimore JR, Hutchinson WL et al.. (2009)
Molecular dissection of Alzheimer's disease neuropathology by depletion of serum amyloid P component.
Proc Natl Acad Sci USA, 106 (18): 7619-23. [PMID:19372378]
4. Pepys MB, Herbert J, Hutchinson WL, Tennent GA, Lachmann HJ, Gallimore JR, Lovat LB, Bartfai T, Alanine A, Hertel C et al.. (2002)
Targeted pharmacological depletion of serum amyloid P component for treatment of human amyloidosis.
Nature, 417 (6886): 254-9. [PMID:12015594]
5. Richards D, Millns H, Cookson L, Lukas MA. (2022)
An observational, non-interventional study for the follow-up of patients with amyloidosis who received miridesap followed by dezamizumab in a phase 1 study.
Orphanet J Rare Dis, 17 (1): 259. [PMID:35810311]
6. Richards DB, Cookson LM, Barton SV, Liefaard L, Lane T, Hutt DF, Ritter JM, Fontana M, Moon JC, Gillmore JD et al.. (2018)
Repeat doses of antibody to serum amyloid P component clear amyloid deposits in patients with systemic amyloidosis.
Sci Transl Med, 10 (422). [PMID:29298867]
7. Schmidt AF, Finan C, Chopade S, Ellmerich S, Rossor MN, Hingorani AD, Pepys MB. (2023)
Genetic evidence for serum amyloid P component as a drug target for treatment of neurodegenerative disorders.
medRxiv, Preprint. DOI: 10.1101/2023.08.15.23293564 [PMID:37645746]
8. Wermuth CG. (2004)
Selective optimization of side activities: another way for drug discovery.
J Med Chem, 47 (6): 1303-14. [PMID:14998318]