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
References
1. Beecher G, Putko BN, Wagner AN, Siddiqi ZA. (2019)
Therapies Directed Against B-Cells and Downstream Effectors in Generalized Autoimmune Myasthenia Gravis: Current Status.
Drugs, 79 (4): 353-364. [PMID:30762205]
2. Howard Jr JF, Bresch S, Genge A, Hewamadduma C, Hinton J, Hussain Y, Juntas-Morales R, Kaminski HJ, Maniaol A, Mantegazza R et al.. (2023)
Safety and efficacy of zilucoplan in patients with generalised myasthenia gravis (RAISE): a randomised, double-blind, placebo-controlled, phase 3 study.
Lancet Neurol, 22 (5): 395-406. [PMID:37059508]
3. Ra Pharmaceuticals. 
Ra Pharmaceuticals Announces Positive Top-line Data from Phase 2 Trial of Zilucoplan in Patients with Generalized Myasthenia Gravis.
Accessed on 11/06/2019. Modified on 11/06/2019. Ra Pharmaceuticals, https://rapharma.gcs-web.com/news-releases/news-release-details/ra-pharmaceuticals-announces-positive-top-line-data-phase-2
4. Shirley M. (2024)
Zilucoplan: First Approval.
Drugs, 84 (1): 99-104. [PMID:38093160]
5. UK Department of Health and Social Care. 
COVID-19 treatments could be fast-tracked through new national clinical trial initiative.
Accessed on 01/06/2020. Modified on 01/06/2020. gov.uk, https://www.gov.uk/government/news/covid-19-treatments-could-be-fast-tracked-through-new-national-clinical-trial-initiative
6. Wilkinson T, Dixon R, Page C, Carroll M, Griffiths G, Ho LP, De Soyza A, Felton T, Lewis KE, Phekoo K et al.. (2020)
ACCORD: A Multicentre, Seamless, Phase 2 Adaptive Randomisation Platform Study to Assess the Efficacy and Safety of Multiple Candidate Agents for the Treatment of COVID-19 in Hospitalised Patients: A structured summary of a study protocol for a randomised controlled trial.
Trials, 21 (1): 691. [PMID:32736596]