Evidence map›Paper›PMID 37622108›Full record

ArticleFrontiers in immunology2023

Zilucoplan, a macrocyclic peptide inhibitor of human complement component 5, uses a dual mode of action to prevent terminal complement pathway activation.

Guo-Qing Tang, Yalan Tang, Ketki Dhamnaskar, Michelle D Hoarty, Rohit Vyasamneni, Douangsone D Vadysirisack, Zhong Ma, Nanqun Zhu, Jian-Guo Wang, Charlie Bu and 5 more

Erratum issuedOpen access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Frontiers in immunology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 26 papers.

0numbers the graph read from it
0cells of the map it votes in
26citing papers in PubMed
6.7field-weighted citation impact, top 3% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

26 citing papers in PubMed, 41 citations in OpenAlex.

  1. Trial
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  5. Phage Display as a Promising Platform for Peptide Drug Discovery.Pharmaceuticals (Basel, Switzerland) · 2026
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  7. Italian recommendations for the diagnosis and treatment of myasthenia gravis.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2026
    Article
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  19. Review
  20. Myasthenia gravis: the future is here.The Journal of clinical investigation · 2024
    Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

15 authors at 1 institution in 1 country.

Guo-Qing TangUCB Pharma, Cambridge, MA, United States.
Yalan TangUCB Pharma, Cambridge, MA, United States.
Ketki DhamnaskarRa Pharmaceuticals, Cambridge, MA, United States.
Michelle D HoartyUCB Pharma/Ra Pharmaceuticals, Cambridge, MA, United States.
Rohit VyasamneniRa Pharmaceuticals, Cambridge, MA, United States.
Douangsone D VadysirisackUCB Pharma/Ra Pharmaceuticals, Cambridge, MA, United States.
Zhong MaUCB Pharma/Ra Pharmaceuticals, Cambridge, MA, United States.
Nanqun ZhuUCB Pharma/Ra Pharmaceuticals, Cambridge, MA, United States.
Jian-Guo WangUCB Pharma, Cambridge, MA, United States.
Charlie BuUCB Pharma, Cambridge, MA, United States.
Bestine CongUCB Pharma, Cambridge, MA, United States.
Elizabeth PalmerUCB Pharma, Cambridge, MA, United States.
Petra W DudaUCB Pharma, Cambridge, MA, United States.
Camil SayeghUCB Pharma/Ra Pharmaceuticals, Cambridge, MA, United States.
Alonso RicardoRa Pharmaceuticals, Cambridge, MA, United States.
UCB Pharma (United States) · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Introduction: The complement system is a key component of the innate immune system, and its aberrant activation underlies the pathophysiology of various diseases. Zilucoplan is a macrocyclic peptide that binds and inhibits the cleavage/activation of human complement component 5 (C5). We present Methods: The interaction of zilucoplan with C5, including for clinical C5 R885 variants, was investigated using surface plasmon resonance (SPR), hemolysis assays, and ELISA. The interference of C5b6 formation by zilucoplan was investigated by native gel analysis and hemolysis assay. The permeability of zilucoplan in a reconstituted basement membrane was assessed by the partition of zilucoplan on Matrigel-coated transwell chambers. Results: Zilucoplan specifically bound human complement C5 with high affinity, competitively inhibited the binding of C5 to C3b, and blocked C5 cleavage by C5 convertases and the assembly of the cytolytic membrane attack complex (MAC, or C5b9). Zilucoplan fully prevented the Conclusion: Our findings demonstrate that zilucoplan uses a dual mode of action to potently inhibit the activation of C5 and terminal complement pathway including wild-type and clinical R885 variants that do not respond to eculizumab treatment. These data may be relevant to the clinically demonstrated benefits of zilucoplan.

Indexed as

Complement ActivationComplement C5HemolysisAntibodies, MonoclonalHumansPeptides, CyclicAntibodies, MonoclonalComplement C5Peptides, CycliczilucoplanC5b6C5 cleavageC5 R885 variantscomplement activationMAC formationmacrocyclic peptide inhibitorpermeabilityRBC hemolysis

Identifiers

PMID37622108
PMCPMC10446491
OpenAlexW4385698347

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.