Zilucoplan

Last updated

Zilucoplan
Zilucoplan structure.svg
Clinical data
Trade names Zilbrysq
Other namesRA101495
License data
Routes of
administration 		Subcutaneous
Drug class Complement inhibitor
ATC code
Legal status
Legal status
Identifiers
  • (2S)-2-[[(2S)-2-[[(2S)-1-[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S,5S,8S,11S,14S,22S)-22-acetamido-11-benzyl-8-(3-carbamimidamidopropyl)-5-(2-carboxyethyl)-3,6,9,12,16,23-hexaoxo-2-propan-2-yl-1,4,7,10,13,17-hexazacyclotricosane-14-carbonyl]-methylamino]-3-carboxypropanoyl]amino]-3,3-dimethylbutanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)propanoyl]amino]-4-carboxybutanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]pyrrolidine-2-carbonyl]amino]-2-cyclohexylacetyl]amino]-6-[3-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[[(4S)-4-carboxy-4-(hexadecanoylamino)butanoyl]amino]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]propanoylamino]hexanoic acid
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEBI
Chemical and physical data
Formula C172H278N24O55
Molar mass 3562.229 g·mol−1
3D model (JSmol)
  • CCCCCCCCCCCCCCCC(=O)N[C@@H](CCC(=O)NCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCC(=O)NCCCC[C@H](NC(=O)[C@@H](NC(=O)[C@@H]1CCCN1C(=O)[C@H](CC1=CC=C(O)C=C1)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC1=CNC2=NC=CC=C12)NC(=O)[C@H](CC1=CC=C(O)C=C1)NC(=O)[C@@H](NC(=O)[C@H](CC(O)=O)N(C)C(=O)[C@@H]1CC(=O)NCCCC[C@H](NC(C)=O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC2=CC=CC=C2)C(=O)N1)C(C)(C)C)C1CCCCC1)C(O)=O)C(O)=O
  • 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
  • Key:JDXCOXKBIGBZSK-PSNKNOTQSA-N

Zilucoplan, sold under the brand name Zilbrysq, is a medication used for the treatment of generalized myasthenia gravis. [1] [4] [5] It is a complement inhibitor that is injected subcutaneously (under the skin). [1]

Contents

Zilucoplan is a cyclic peptide that binds to the protein complement component 5 (C5) and inhibits its cleavage into C5a and C5b. [6]

Zilucoplan was approved for medical use in the United States in October 2023, [1] [7] and in the European Union in December 2023. [2]

Medical uses

Zilucoplan is indicated for the treatment of generalized myasthenia gravis in adults who are anti-acetylcholine receptor antibody positive. [1]

Society and culture

In September 2023, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) adopted a positive opinion, recommending the granting of a marketing authorization for the medicinal product Zilbrysq, intended for the treatment of myasthenia gravis. [8] The applicant for this medicinal product is UCB Pharma S.A. [8] Zilucoplan was approved for medical use in the Europea Union in December 2023. [2]

Zilucoplan was granted orphan drug designation by the US Food and Drug Administration (FDA) in August 2019, [9] and by the EMA in July 2022. [10]

Brand names

Zilucoplan is the international nonproprietary name. [11]

Zilucoplan is sold under the brand name Zilbrysq. [2]

Related Research Articles

<span class="mw-page-title-main">Myasthenia gravis</span> Autoimmune disease resulting in skeletal muscle weakness

Myasthenia gravis (MG) is a long-term neuromuscular junction disease that leads to varying degrees of skeletal muscle weakness. The most commonly affected muscles are those of the eyes, face, and swallowing. It can result in double vision, drooping eyelids, and difficulties in talking and walking. Onset can be sudden. Those affected often have a large thymus or develop a thymoma.

Eculizumab, sold under the brand name Soliris among others, is a recombinant humanized monoclonal antibody used to treat paroxysmal nocturnal hemoglobinuria (PNH), atypical hemolytic uremic syndrome (aHUS), generalized myasthenia gravis, and neuromyelitis optica. In people with PNH, it reduces both the destruction of red blood cells and need for blood transfusion, but does not appear to affect the risk of death. Eculizumab was the first drug approved for each of its uses, and its approval was granted based on small trials. It is given by intravenous infusion.

Enfortumab vedotin, sold under the brand name Padcev, is an antibody-drug conjugate used for the treatment of urothelial cancer. It is a nectin-4-directed antibody and microtubule inhibitor conjugate. Enfortumab refers to the monoclonal antibody part, and vedotin refers to the payload drug (MMAE) and the linker.

<span class="mw-page-title-main">Acalabrutinib</span> Chemical compound

Acalabrutinib, sold under the brand name Calquence, is a medication used to treat various types of non-Hodgkin lymphoma, including mantle cell lymphoma (MCL) and chronic lymphocytic leukemia/small lymphocytic Lymphoma (CLL/SLL). It may be used both in relapsed as well as in treatment-naive settings.

<span class="mw-page-title-main">Glasdegib</span> Treatment for acute myeloid leukemia

Glasdegib, sold under the brand name Daurismo, is a medication for the treatment of newly-diagnosed acute myeloid leukemia (AML) in adults older than 75 years or those who have comorbidities that preclude use of intensive induction chemotherapy. It is taken by mouth and is used in combination with low-dose cytarabine.

<span class="mw-page-title-main">Ivosidenib</span> Anti-cancer medication

Ivosidenib, sold under the brand name Tibsovo, is an anti-cancer medication for the treatment of acute myeloid leukemia (AML) and cholangiocarcinoma. It is a small molecule inhibitor of isocitrate dehydrogenase-1 (IDH1), which is mutated in several forms of cancer. Ivosidenib is an isocitrate dehydrogenase-1 inhibitor that works by decreasing abnormal production of the oncometabolite 2-hydroxyglutarate (2-HG), leading to differentiation of malignant cells.

Ravulizumab, sold under the brand name Ultomiris, is a humanized monoclonal antibody complement inhibitor medication designed for the treatment of paroxysmal nocturnal hemoglobinuria (PNH) and atypical hemolytic uremic syndrome. It is designed to bind to and prevent the activation of Complement component 5 (C5).

Sutimlimab, sold under the brand name Enjaymo, is a monoclonal antibody that is used to treat adults with cold agglutinin disease (CAD). It is given by intravenous infusion. Sutimlimab prevents complement-enhanced activation of autoimmune human B cells in vitro.

<span class="mw-page-title-main">Pemigatinib</span> Pharmaceutical drug

Pemigatinib, sold under the brand name Pemazyre, is an anti-cancer medication used for the treatment of bile duct cancer (cholangiocarcinoma). Pemigatinib works by blocking FGFR2 in tumor cells to prevent them from growing and spreading.

<span class="mw-page-title-main">Ripretinib</span> Chemical compound

Ripretinib, sold under the brand name Qinlock, is a medication for the treatment of adults with advanced gastrointestinal stromal tumor (GIST), a type of tumor that originates in the gastrointestinal tract. It is taken by mouth. Ripretinib inhibits the activity of the kinases KIT and PDGFRA, which helps keep cancer cells from growing.

Pegcetacoplan, sold under the brand name Empaveli, among others, is a medication used to treat paroxysmal nocturnal hemoglobinuria and geographic atrophy of the retina. Pegcetacoplan is a complement inhibitor.

<span class="mw-page-title-main">Maralixibat chloride</span> Chemical compound

Maralixibat chloride, sold under the brand name Livmarli, is a medication used to treat cholestatic pruritus in people with Alagille syndrome. Maralixibat chloride is an ileal bile acid transporter (IBAT) inhibitor.

<span class="mw-page-title-main">Avacopan</span> Chemical compound

Avacopan, sold under the brand name Tavneos, is a medication used to treat anti-neutrophil cytoplasmic autoantibody-associated vasculitis. Avacopan is a complement 5a receptor antagonist and a cytochrome P450 3A4 inhibitor.

<span class="mw-page-title-main">Asciminib</span> Chemical compound

Asciminib, sold under the brand name Scemblix, is a medication used to treat Philadelphia chromosome-positive chronic myeloid leukemia. Asciminib is a protein kinase inhibitor.

Efgartigimod alfa, sold under the brand name Vyvgart, is a medication used to treat myasthenia gravis. Efgartigimod alfa is a neonatal Fc receptor blocker and is a new class of medication. It is an antibody fragment that binds to the neonatal Fc receptor (FcRn), preventing FcRn from recycling immunoglobulin G (IgG) back into the blood. The medication causes a reduction in overall levels of IgG, including the abnormal acetylcholine receptor (AChR) antibodies that are present in myasthenia gravis. It is also available coformulated with hyaluronidase.

Epcoritamab, sold under the brand name Epkinly, is a monoclonal antibody anticancer medication used for the treatment of diffuse large B-cell lymphoma. Epcoritamab is a bispecific CD20-directed CD3 T-cell engager. Epcoritamab was co-developed by AbbVie and Genmab.

Efgartigimod alfa/hyaluronidase, sold under the brand name Vyvgart Hytrulo, is a coformulation medication used for the treatment of generalized myasthenia gravis. It contains efgartigimod alfa, a neonatal Fc receptor blocker, and hyaluronidase, an endoglycosidase.

Rozanolixizumab, sold under the brand name Rystiggo, is a monoclonal antibody used for the treatment of myasthenia gravis. Rozanolixizumab is a humanized and chimeric monoclonal antibody; and is a neonatal Fc receptor blocker.

Elranatamab, sold under the brand name Elrexfio, is a medication used for the treatment of multiple myeloma. Elranatamab is a bispecific B-cell maturation antigen (BCMA)-directed CD3 T-cell engager. Elranatamab is administered subcutaneously.

Palopegteriparatide, sold under the brand name Yorvipath, is a hormone replacement therapy used for the treatment of chronic hypoparathyroidism. It is a transiently pegylated parathyroid hormone.

References

  1. 1 2 3 4 5 "Zilbrysq (zilucoplan) injection, for subcutaneous use" (PDF). Archived (PDF) from the original on 19 October 2023. Retrieved 19 October 2023.
  2. 1 2 3 4 "Zilbrysq EPAR". European Medicines Agency. 1 December 2023. Retrieved 11 December 2023.
  3. ↑ "Zilbrysq Product information". Union Register of medicinal products. 4 December 2023. Archived from the original on 11 December 2023. Retrieved 11 December 2023.
  4. ↑ Howard JF, Kaminski HJ, Nowak RJ, Wolfe GI, Benatar MG, Ricardo A, et al. (April 2018). "RA101495, a subcutaneously administered peptide inhibitor of complement component 5 (C5) for the treatment of generalized myasthenia gravis (gMG): Phase 1 results and phase 2 design (S31. 006)". Neurology. 90 (15 Supplement). doi:10.1212/WNL.90.15_supplement.S31.006. S2CID   56969245. Archived from the original on 22 February 2022. Retrieved 24 June 2021.
  5. ↑ Howard JF, Vissing J, Gilhus NE, Leite MI, Utsugisawa K, Duda PW, et al. (May 2021). "Zilucoplan: An Investigational Complement C5 Inhibitor for the Treatment of Acetylcholine Receptor Autoantibody-Positive Generalized Myasthenia Gravis". Expert Opinion on Investigational Drugs. 30 (5): 483–493. doi: 10.1080/13543784.2021.1897567 . hdl: 11250/2770699 . PMID   33792453. S2CID   232482753.
  6. ↑ Ricardo A, Arata M, DeMarco S, Dhamnaskar K, Hammer R, Fridkis-Hareli M, et al. (2015). "Preclinical Evaluation of RA101495, a Potent Cyclic Peptide Inhibitor of C5 for the Treatment of Paroxysmal Nocturnal Hemoglobinuria". Blood. 126 (23): 939. doi:10.1182/blood.V126.23.939.939.
  7. ↑ "Novel Drug Approvals for 2023". U.S. Food and Drug Administration (FDA). 22 December 2023. Retrieved 27 December 2023.
  8. 1 2 "Zilbrysq: Pending EC decision". European Medicines Agency. 15 September 2023. Archived from the original on 26 September 2023. Retrieved 24 September 2023. Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
  9. ↑ "Zilucoplan Orphan Drug Designations and Approvals". U.S. Food and Drug Administration (FDA). Archived from the original on 17 October 2023. Retrieved 19 October 2023.
  10. ↑ "EU/3/22/2650: Orphan designation for the treatment of myasthenia gravis". European Medicines Agency. 15 September 2023. Archived from the original on 29 January 2023. Retrieved 24 September 2023.
  11. ↑ World Health Organization (2018). "International nonproprietary names for pharmaceutical substances (INN): recommended INN: list 80". WHO Drug Information. 32 (3). hdl: 10665/330907 .
This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.