Target Information
| Target General Information | Top | |||||
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| Target ID |
T37742
(Former ID: TTDR00446)
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| Target Name |
Serum amyloid P-component (APCS)
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| Synonyms |
SAP; APCS; 9.5S alpha-1-glycoprotein
Click to Show/Hide
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| Gene Name |
APCS
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| Target Type |
Clinical trial target
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[1] | ||||
| Disease | [+] 1 Target-related Diseases | + | ||||
| 1 | Idiopathic interstitial pneumonitis [ICD-11: CB03] | |||||
| Function |
Can interact with DNA and histones and may scavenge nuclear material released from damaged circulating cells. May also function as a calcium-dependent lectin.
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| BioChemical Class |
Pentraxin family
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| UniProt ID | ||||||
| Sequence |
MNKPLLWISVLTSLLEAFAHTDLSGKVFVFPRESVTDHVNLITPLEKPLQNFTLCFRAYS
DLSRAYSLFSYNTQGRDNELLVYKERVGEYSLYIGRHKVTSKVIEKFPAPVHICVSWESS SGIAEFWINGTPLVKKGLRQGYFVEAQPKIVLGQEQDSYGGKFDRSQSFVGEIGDLYMWD SVLPPENILSAYQGTPLPANILDWQALNYEIRGYVIIKPLVWV Click to Show/Hide
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| 3D Structure | Click to Show 3D Structure of This Target | PDB | ||||
| Drugs and Modes of Action | Top | |||||
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| Clinical Trial Drug(s) | [+] 4 Clinical Trial Drugs | + | ||||
| 1 | Zinpentraxin alfa | Drug Info | Phase 3 | Idiopathic pulmonary fibrosis | [2] | |
| 2 | CPHPC | Drug Info | Phase 1/2 | Parkinson disease | [3], [4] | |
| 3 | GSK-2315698 | Drug Info | Phase 1 | Amyloidosis | [5] | |
| 4 | GSK2398852 | Drug Info | Phase 1 | Amyloidosis | [5], [6] | |
| Mode of Action | [+] 2 Modes of Action | + | ||||
| Replacement | [+] 1 Replacement drugs | + | ||||
| 1 | Zinpentraxin alfa | Drug Info | [7] | |||
| Modulator | [+] 1 Modulator drugs | + | ||||
| 1 | CPHPC | Drug Info | [1] | |||
| Cell-based Target Expression Variations | Top | |||||
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| Cell-based Target Expression Variations | ||||||
| Drug Binding Sites of Target | Top | |||||
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| Ligand Name: CPHPC | Ligand Info | |||||
| Structure Description | Structure of CPHPC bound to Serum Amyloid P Component | PDB:4AVV | ||||
| Method | X-ray diffraction | Resolution | 1.60 Å | Mutation | No | [1] |
| PDB Sequence |
HTDLSGKVFV
10 FPRESVTDHV20 NLITPLEKPL30 QNFTLCFRAY40 SDLSRAYSLF50 SYNTQGRDNE 60 LLVYKERVGE70 YSLYIGRHKV80 TSKVIEKFPA90 PVHICVSWES100 SSGIAEFWIN 110 GTPLVKKGLR120 QGYFVEAQPK130 IVLGQEQDSY140 GGKFDRSQSF150 VGEIGDLYMW 160 DSVLPPENIL170 SAYQGTPLPA180 NILDWQALNY190 EIRGYVIIKP200 LVWV |
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| Ligand Name: O-Phosphoethanolamine | Ligand Info | |||||
| Structure Description | The structure of serum amyloid p component bound to phosphoethanolamine | PDB:3KQR | ||||
| Method | X-ray diffraction | Resolution | 1.50 Å | Mutation | No | [10] |
| PDB Sequence |
HTDLSGKVFV
10 FPRESVTDHV20 NLITPLEKPL30 QNFTLCFRAY40 SDLSRAYSLF50 SYNTQGRDNE 60 LLVYKERVGE70 YSLYIGRHKV80 TSKVIEKFPA90 PVHICVSWES100 SSGIAEFWIN 110 GTPLVKKGLR120 QGYFVEAQPK130 IVLGQEQDSY140 GGKFDRSQSF150 VGEIGDLYMW 160 DSVLPPENIL170 SAYQGTPLPA180 NILDWQALNY190 EIRGYVIIKP200 LVWV |
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| Click to View More Binding Site Information of This Target with Different Ligands | ||||||
| Different Human System Profiles of Target | Top |
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Human Similarity Proteins
of target is determined by comparing the sequence similarity of all human proteins with the target based on BLAST. The similarity proteins for a target are defined as the proteins with E-value < 0.005 and outside the protein families of the target.
A target that has fewer human similarity proteins outside its family is commonly regarded to possess a greater capacity to avoid undesired interactions and thus increase the possibility of finding successful drugs
(Brief Bioinform, 21: 649-662, 2020).
Human Tissue Distribution
of target is determined from a proteomics study that quantified more than 12,000 genes across 32 normal human tissues. Tissue Specificity (TS) score was used to define the enrichment of target across tissues.
The distribution of targets among different tissues or organs need to be taken into consideration when assessing the target druggability, as it is generally accepted that the wider the target distribution, the greater the concern over potential adverse effects
(Nat Rev Drug Discov, 20: 64-81, 2021).
Human Similarity Proteins
Human Tissue Distribution
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There is no similarity protein (E value < 0.005) for this target
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Note:
If a protein has TS (tissue specficity) scores at least in one tissue >= 2.5, this protein is called tissue-enriched (including tissue-enriched-but-not-specific and tissue-specific). In the plots, the vertical lines are at thresholds 2.5 and 4.
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| Target Profiles in Patients | Top | |||||
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| Target Expression Profile (TEP) | ||||||
| Target Affiliated Biological Pathways | Top | |||||
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| Reactome | [+] 1 Reactome Pathways | + | ||||
| 1 | Amyloid formation | |||||
| WikiPathways | [+] 2 WikiPathways | + | ||||
| 1 | Human Complement System | |||||
| 2 | Amyloids | |||||
| References | Top | |||||
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| REF 1 | Interaction of serum amyloid P component with hexanoyl bis(D-proline) (CPHPC).Acta Crystallogr D Biol Crystallogr.2014 Aug;70(Pt 8):2232-40. | |||||
| REF 2 | ClinicalTrials.gov (NCT04552899) A Phase III Randomized, Double-blind, Placebo Controlled Trial to Evaluate the Efficacy and Safety of PRM-151 in Patients With Idiopathic Pulmonary Fibrosis. U.S.National Institutes of Health. | |||||
| REF 3 | URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 8256). | |||||
| REF 4 | ClinicalTrials.gov (NCT02425241) Depletion of Serum Amyloid P Component to Enhance the Immune Response to DNA Vaccination. U.S. National Institutes of Health. | |||||
| REF 5 | ClinicalTrials.gov (NCT01777243) A Study to Evaluate the Safety of GSK2398852 When Co-administered With GSK2315698 in Patients With Systemic Amyloidosis. U.S. National Institutes of Health. | |||||
| REF 6 | URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 8255). | |||||
| REF 7 | Safety and efficacy of zinpentraxin alfa as monotherapy or in combination with ruxolitinib in myelofibrosis: stage I of a phase II trial. Haematologica. 2023 Oct 1;108(10):2730-2742. | |||||
| REF 8 | Target Mediated Drug Disposition Model of CPHPC in Patients with Systemic Amyloidosis. CPT Pharmacometrics Syst Pharmacol. 2015 February; 4(2): e15. | |||||
| REF 9 | PRM-151 (recombinant human serum amyloid P/pentraxin 2) for the treatment of fibrosis. Drug News Perspect. 2010 Jun;23(5):305-15. | |||||
| REF 10 | Structural basis of ligand specificity in the human pentraxins, C-reactive protein and serum amyloid P component. J Mol Recognit. 2011 Mar-Apr;24(2):371-7. | |||||
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