zilucoplan   Click here for help

GtoPdb Ligand ID: 10404

Synonyms: RA-101495 | RA101495 | Zilbrysq®
Approved drug Immunopharmacology Ligand
zilucoplan is an approved drug (FDA & EMA (2023))
Compound class: Peptide or derivative
Comment: Zilucoplan (RA101495) is a synthetic, macrocyclic peptide that blocks the cleavage of complement C5 into C5a and C5b which occurs as a consequence of activation of the classical, alternative, or lectin pathways. This mechanism of action inhibits formation of the membrane attack complex (MAC). It was developed by RaPharma for the treatment of tissue-based complement-mediated disorders.
2D Structure
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2D Structure

An image of the ligand's 2D structure. For small molecules with SMILES these are drawn using the NCI/CADD Chemical Identifier Resolver. Click on the image to access the chemical structure search tool with the ligand pre-loaded in the structure editor. For other types of ligands, e.g. longer nucleotides and peptides, a manually drawn representation of the molecule may be provided.

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SMILES / InChI / InChIKey
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SMILES / InChI / InChIKey

SMILES (Simplified Molecular Input Line Entry Specification) A specification for unambiguously describing the structure of chemical molecules using short ASCII strings. Canonical SMILES specify a unique representation of the 2D structure without chiral or isotopic specifications. Isomeric SMILES include chiral specification and isotopes.

Standard InChI (IUPAC International Chemical Identifier) and InChIKey InChI is a non-proprietary, standard, textual identifier for chemical substances designed to facilitate linking of information and database searching. An InChIKey is a simplified version of a full InChI, designed for easier web searching.

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Canonical SMILES CCCCCCCCCCCCCCCC(=O)NC(C(=O)O)CCC(=O)NCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCC(=O)NCCCCC(C(=O)O)NC(=O)C(C1CCCCC1)NC(=O)C1CCCN1C(=O)C(NC(=O)C(NC(=O)C(Cc1c[nH]c2c1cccn2)NC(=O)C(NC(=O)C(C(C)(C)C)NC(=O)C(N(C(=O)C1CC(=O)NCCCCC(NC(=O)C)C(=O)NC(C(=O)NC(C(=O)NC(C(=O)NC(C(=O)N1)Cc1ccccc1)CCCNC(=N)N)CCC(=O)O)C(C)C)C)CC(=O)O)Cc1ccc(cc1)O)CCC(=O)O)Cc1ccc(cc1)O
Isomeric SMILES CCCCCCCCCCCCCCCC(=O)N[C@H](C(=O)O)CCC(=O)NCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCC(=O)NCCCC[C@@H](C(=O)O)NC(=O)[C@H](C1CCCCC1)NC(=O)[C@@H]1CCCN1C(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@H](Cc1c[nH]c2c1cccn2)NC(=O)[C@@H](NC(=O)[C@H](C(C)(C)C)NC(=O)[C@@H](N(C(=O)[C@@H]1CC(=O)NCCCC[C@H](NC(=O)C)C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@H](C(=O)N1)Cc1ccccc1)CCCNC(=N)N)CCC(=O)O)C(C)C)C)CC(=O)O)Cc1ccc(cc1)O)CCC(=O)O)Cc1ccc(cc1)O
InChI InChI=1S/C172H278N24O55/c1-9-10-11-12-13-14-15-16-17-18-19-20-27-44-146(202)182-136(170(226)227)53-56-144(200)177-64-67-229-69-71-231-73-75-233-77-79-235-81-83-237-85-87-239-89-91-241-93-95-243-97-99-245-101-103-247-105-107-249-109-111-251-113-112-250-110-108-248-106-104-246-102-100-244-98-96-242-94-92-240-90-88-238-86-84-236-82-80-234-78-76-232-74-72-230-70-68-228-66-59-145(201)175-60-31-29-41-135(169(224)225)186-165(220)152(126-37-25-22-26-38-126)193-162(217)142-43-34-65-196(142)168(223)140(116-125-47-51-129(199)52-48-125)190-157(212)133(54-57-148(204)205)184-161(216)139(117-127-120-180-154-130(127)39-32-62-178-154)188-159(214)138(115-124-45-49-128(198)50-46-124)189-166(221)153(172(5,6)7)194-163(218)143(119-150(208)209)195(8)167(222)141-118-147(203)176-61-30-28-40-131(181-122(4)197)158(213)192-151(121(2)3)164(219)185-134(55-58-149(206)207)156(211)183-132(42-33-63-179-171(173)174)155(210)187-137(160(215)191-141)114-123-35-23-21-24-36-123/h21,23-24,32,35-36,39,45-52,62,120-121,126,131-143,151-153,198-199H,9-20,22,25-31,33-34,37-38,40-44,53-61,63-119H2,1-8H3,(H,175,201)(H,176,203)(H,177,200)(H,178,180)(H,181,197)(H,182,202)(H,183,211)(H,184,216)(H,185,219)(H,186,220)(H,187,210)(H,188,214)(H,189,221)(H,190,212)(H,191,215)(H,192,213)(H,193,217)(H,194,218)(H,204,205)(H,206,207)(H,208,209)(H,224,225)(H,226,227)(H4,173,174,179)/t131-,132-,133-,134-,135-,136-,137-,138-,139-,140-,141-,142-,143-,151-,152-,153+/m0/s1
InChI Key JDXCOXKBIGBZSK-PSNKNOTQSA-N
No information available.
Summary of Clinical Use Click here for help
Zilucoplan was progressed to clinical evaluation in paroxysmal nocturnal hemoglobinuria (PNH) and generalized myasthenia gravis (gMG) [1]. Click here to link to ClinicalTrials.gov's full list of zilucoplan trials. The earliest approval for gMG was issued in Japan in September 2023 [4], with FDA approval following in October, and EMA authorisation in December.

In response to the SARS-CoV-2 pandemic plans were made to evaluate zilucoplan in COVID-19 patients, as part of the UK's Accelerating COVID-19 Research and Development (ACCORD) initiative (June 2020). ACCORD aims to fast-track potential treatments for COVID-19 through early-stage clinical trials [5-6]. The first candidate agents included in the ACCORD study were 10478, MEDI3506 (tozorakimab, and anti-IL33 mAb), acalabrutinib, zilucoplan and nebulised heparin. Through this study researchers would aim to determine if the anti-inflammatory action mediated by zilucoplan has efficacy to reduce mortality in patients with severe COVID-19.

In October 2023 the FDA approved zilucoplan to treat gMG in patients with acetylcholine receptor autoantibodies.
Clinical Trials
Clinical Trial ID Title Type Source Comment References
NCT04225871 Open-Label Extension of Zilucoplan in Subjects With Generalized Myasthenia Gravis Phase 3 Interventional UCB Pharma
NCT04115293 Safety, Tolerability, and Efficacy of Zilucoplan in Subjects With Generalized Myasthenia Gravis Phase 3 Interventional UCB Pharma 2
External links Click here for help
For extended ADME data see the following:

European Medicines Agency (EMA)