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Identification
NameRilonacept
Accession NumberDB06372
Typebiotech
Groupsapproved
Description

Rilonacept is a dimeric fusion protein consisting of portions of IL-1R and the IL-1R accessory
protein linked to the Fc portion of immunoglobulin G1. Rilonacept functions as an interleukin 1 inhibitor and is used in the treatment of CAPS, also known as cryopyrin-associated periodic syndromes, including familial cold auto-inflammatory syndrome (FCAS) and Muckle-Wells Syndrome (MWS), in adults and children greater than 12 years old.

Protein structureNo structure small
Protein chemical formulaC9030H13932N2400O2670S74
Protein average weight 251 kDa
Sequences
>8750_M|rilonacept|Homo sapiens||FUSION-IL1RAP-IL1R1-GAMMA-1 (IL1RAP+(Pr21-359)(1-339)+IL1R1+(Pr22-333)(340-651)+HINGE-REGION(652-663)+CH2(664-773)+CH3(774-880))|||||||880||||MW 100630.6|MW 100630.6|
SERCDDWGLDTMRQIQVFEDEPARIKCPLFEHFLKFNYSTAHSAGLTLIWYWTRQDRDLE
EPINFRLPENRISKEKDVLWFRPTLLNDTGNYTCMLRNTTYCSKVAFPLEVVQKDSCFNS
PMKLPVHKLYIEYGIQRITCPNVDGYFPSSVKPTITWYMGCYKIQNFNNVIPEGMNLSFL
IALISNNGNYTCVVTYPENGRTFHLTRTLTVKVVGSPKNAVPPVIHSPNDHVVYEKEPGE
ELLIPCTVYFSFLMDSRNEVWWTIDGKKPDDITIDVTINESISHSRTEDETRTQILSIKK
VTSEDLKRSYVCHARSAKGEVAKAAKVKQKVPAPRYTVEKCKEREEKIILVSSANEIDVR
PCPLNPNEHKGTITWYKDDSKTPVSTEQASRIHQHKEKLWFVPAKVEDSGHYYCVVRNSS
YCLRIKISAKFVENEPNLCYNAQAIFKQKLPVAGDGGLVCPYMEFFKNENNELPKLQWYK
DCKPLLLDNIHFSGVKDRLIVMNVAEKHRGNYTCHASYTYLGKQYPITRVIEFITLEENK
PTRPVIVSPANETMEVDLGSQIQLICNVTGQLSDIAYWKWNGSVIDEDDPVLGEDYYSVE
NPANKRRSTLITVLNISEIESRFYKHPFTCFAKNTHGIDAAYIQLIYPVTNSGDKTHTCP
PCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNA
KTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQ
VYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLY
SKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK
Download FASTA Format
Synonyms
SynonymLanguageCode
ArcalystNot AvailableNot Available
interleukin-1 (IL-1) trapNot AvailableNot Available
SaltsNot Available
Brand names
NameCompany
ArcalystRegeneron
Brand mixturesNot Available
Categories
CAS number501081-76-1
Taxonomy
KingdomOrganic Compounds
SuperclassOrganic Acids
ClassCarboxylic Acids and Derivatives
SubclassAmino Acids, Peptides, and Analogues
Direct parentPeptides
Alternative parentsNot Available
SubstituentsNot Available
Classification descriptionNot Available
Pharmacology
IndicationRilonacept is currently used in the treatment of cryopyrin-associated periodic syndrome. In May 2012, an advisory panel for the FDA voted 11-0 against the use of Rilonacept for the treatment of gout.
PharmacodynamicsTreatment with Rilonacept resulted in decreased levels of mean C-Reactive Protein (CRP) and Serum Amyloid A (SAA). Higher levels of CRP and SAA are associated with inflammatory disease activity found in patients with Cryopyrin-Associated Periodic Syndromes.
Mechanism of actionCAPS refer to rare genetic syndromes generally caused by mutations in the NLRP-3 [Nucleotide-binding domain, leucine rich family (NLR), pyrin domain containing 3] gene (also known as Cold-Induced Auto-inflammatory Syndtrome-1 [CIAS1]). CAPS disorders are inherited in an autosomal dominant pattern with male and female offspring equally affected. Fever, urticaria-like rash, arthralgia, myalgia, fatigue, and conjunctivitis are features common to all disorders. In most cases, inflammation in CAPS is associated with mutations in the NLRP-3 gene which encodes the protein cryopyrin, an important component of the inflammasome. Cryopyrin regulates the protease caspase-1 and controls the activation of interleukin-1 beta (IL-1β). Mutations in NLRP-3 result in an overactive inflammasome resulting in excessive release of activated IL-1β that drives inflammation. Rilonacept blocks IL-1β signaling by acting as a soluble decoy receptor that binds IL-1β and prevents its interaction with cell surface receptors. Rilonacept also binds IL-1α and IL-1 receptor antagonist (IL-1ra) with reduced affinity. By binding IL-1, rilonacept prevents the activation of IL-1 receptors, thus reducing inflammatory responses and other effects related to an excess of IL-1.
AbsorptionNot Available
Volume of distributionNot Available
Protein bindingNot Available
Metabolism
Route of eliminationNot Available
Half life8.6 days
ClearanceNot Available
ToxicityNot Available
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage forms
FormRouteStrength
Injection, powder, lyophilized, for solutionSubcutaneous220mg
PricesNot Available
Patents
CountryPatent NumberApprovedExpires (estimated)
United States58440992008-02-272020-01-01
United States81143942008-02-272020-01-01
United States80802482008-02-272020-01-01
Properties
Statesolid
Experimental PropertiesNot Available
References
Synthesis Reference

Rilonacept is expressed in recombinant Chinese hamster ovary (CHO) cells.

General Reference
  1. Hoffman HM, Throne ML, Amar NJ, Cartwright RC, Kivitz AJ, Soo Y, Weinstein SP: Long-term efficacy and safety profile of rilonacept in the treatment of cryopryin-associated periodic syndromes: results of a 72-week open-label extension study. Clin Ther. 2012 Oct;34(10):2091-103. doi: 10.1016/j.clinthera.2012.09.009. Epub 2012 Sep 29. Pubmed
  2. Tran TH, Pham JT, Shafeeq H, Manigault KR, Arya V: Role of Interleukin-1 Inhibitors in the Management of Gout. Pharmacotherapy. 2013 Apr 3. doi: 10.1002/phar.1265. Pubmed
  3. Hawkins PN, Lachmann HJ, McDermott MF: Interleukin-1-receptor antagonist in the Muckle-Wells syndrome. N Engl J Med. 2003 Jun 19;348(25):2583-4. Pubmed
  4. Cronstein BN, Sunkureddi P: Mechanistic aspects of inflammation and clinical management of inflammation in acute gouty arthritis. J Clin Rheumatol. 2013 Jan;19(1):19-29. doi: 10.1097/RHU.0b013e31827d8790. Pubmed
External Links
ResourceLink
RxListhttp://www.rxlist.com/arcalyst-drug.htm
Drugs.comhttp://www.drugs.com/ppa/rilonacept.html
WikipediaRilonacept
ATC CodesNot Available
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelshow(148 KB)
MSDSshow(568 KB)
Interactions
Drug Interactions
Drug
Adalimumabresults in increased immunosuppressive effects; increases the risk of infection.
Alefaceptresults in increased immunosuppressive effects; increases the risk of infection.
Anakinraresults in increased immunosuppressive effects; increases the risk of infection.
Antithymocyte globulinresults in increased immunosuppressive effects; increases the risk of infection.
Azathioprineresults in increased immunosuppressive effects; increases the risk of infection.
Basiliximabresults in increased immunosuppressive effects; increases the risk of infection.
BelataceptBelatacept decreases immunosuppressive effects while rilonacept increases immunosuppressive effects. Potential risk of infection although the effect of interaction is not known; use caution and monitor closely if using both.
BelataceptBelatacept decreases immunosuppressive effects while rilonacept increases immunosuppressive effects. Potential risk of infection although the effect of interaction is not known; use caution and monitor closely if using both.
BelataceptBelatacept decreases immunosuppressive effects while rilonacept increases immunosuppressive effects. Potential risk of infection although the effect of interaction is not known; use caution and monitor closely if using both.
Canakinumabresults in increased immunosuppressive effects; increases the risk of infection.
Cyclosporineresults in increased immunosuppressive effects; increases the risk of infection.
Daclizumabresults in increased immunosuppressive effects; increases the risk of infection.
Denileukin diftitoxdecreases effects of toxoids by pharmacodynamic antagonism.
DenosumabUse caution with patients on concomitant immunosuppressants or those with compromised immune systems; increased risk of serious infection.
Efalizumabresults in increased immunosuppressive effects; increases the risk of infection.
Etanerceptresults in increased immunosuppressive effects; increases the risk of infection.
Everolimusresults in increased immunosuppressive effects; increases the risk of infection.
Glatiramer Acetateresults in increased immunosuppressive effects; increases the risk of infection.
golimumabresults in increased immunosuppressive effects; increases the risk of infection.
golimumabAvoid combination due to the enhancement of rilonacept associated side effects.
Hydroxychloroquineresults in increased immunosuppressive effects; increases the risk of infection.
Infliximabresults in increased immunosuppressive effects; increases the risk of infection.
Leflunomideresults in increased immunosuppressive effects; increases the risk of infection.
MethotrexateRilonacept and methotrexate both increase immunosuppressive effects; combination may increase risk of myelosuppression.
Muromonabresults in increased immunosuppressive effects; increases the risk of infection.
Mycophenolate mofetilresults in increased immunosuppressive effects; increases the risk of infection.
Sipuleucel-Tdecreases effectiveness of APC8015 by pharmacodynamic antagonism.
Sirolimusresults in increased immunosuppressive effects; increases the risk of infection.
Tacrolimusresults in increased immunosuppressive effects; increases the risk of infection.
Temsirolimusresults in increased immunosuppressive effects; increases the risk of infection.
ThalidomideThalidomide may increase the adverse effects of Rilonacept. Increased risk of serious infection. Concomitant therapy should be avoided.
Tocilizumabresults in increased immunosuppressive effects; increases the risk of infection.
TrastuzumabTrastuzumab may increase the risk of neutropenia and anemia. Monitor closely for signs and symptoms of adverse events.
Food InteractionsNot Available

Targets

1. Interleukin-1 beta

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: binder

Components

Name UniProt ID Details
Interleukin-1 beta P01584 Details

References:

  1. Tran TH, Pham JT, Shafeeq H, Manigault KR, Arya V: Role of Interleukin-1 Inhibitors in the Management of Gout. Pharmacotherapy. 2013 Apr 3. doi: 10.1002/phar.1265. Pubmed
  2. Cronstein BN, Sunkureddi P: Mechanistic aspects of inflammation and clinical management of inflammation in acute gouty arthritis. J Clin Rheumatol. 2013 Jan;19(1):19-29. doi: 10.1097/RHU.0b013e31827d8790. Pubmed

2. Interleukin-1 alpha

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: binder

Components

Name UniProt ID Details
Interleukin-1 alpha P01583 Details

References:

  1. Tran TH, Pham JT, Shafeeq H, Manigault KR, Arya V: Role of Interleukin-1 Inhibitors in the Management of Gout. Pharmacotherapy. 2013 Apr 3. doi: 10.1002/phar.1265. Pubmed
  2. Cronstein BN, Sunkureddi P: Mechanistic aspects of inflammation and clinical management of inflammation in acute gouty arthritis. J Clin Rheumatol. 2013 Jan;19(1):19-29. doi: 10.1097/RHU.0b013e31827d8790. Pubmed

3. Interleukin-1 receptor antagonist protein

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: binder

Components

Name UniProt ID Details
Interleukin-1 receptor antagonist protein P18510 Details

References:

  1. Hawkins PN, Lachmann HJ, McDermott MF: Interleukin-1-receptor antagonist in the Muckle-Wells syndrome. N Engl J Med. 2003 Jun 19;348(25):2583-4. Pubmed
  2. Cronstein BN, Sunkureddi P: Mechanistic aspects of inflammation and clinical management of inflammation in acute gouty arthritis. J Clin Rheumatol. 2013 Jan;19(1):19-29. doi: 10.1097/RHU.0b013e31827d8790. Pubmed

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Drug created on March 19, 2008 10:27 / Updated on August 06, 2013 15:43