You are using an unsupported browser. Please upgrade your browser to a newer version to get the best experience on DrugBank.
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 354e4808da70a5bd16896d40d8e7c4c304b2c46d0efa4be7aa608033bb036952
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
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Arcalystinjection, powder, lyophilized, for solution160 mg/2mLsubcutaneousRegeneron Pharmaceuticals, Inc.2008-02-27Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Generic Prescription ProductsNot Available
Over the Counter ProductsNot Available
International BrandsNot Available
Brand mixturesNot Available
SaltsNot Available
Categories
CAS number501081-76-1
Taxonomy
DescriptionNot Available
KingdomOrganic Compounds
Super ClassOrganic Acids
ClassCarboxylic Acids and Derivatives
Sub ClassAmino Acids, Peptides, and Analogues
Direct ParentPeptides
Alternative ParentsNot Available
SubstituentsNot Available
Molecular FrameworkNot Available
External DescriptorsNot 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
MetabolismNot Available
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 solutionsubcutaneous160 mg/2mL
PricesNot Available
Patents
CountryPatent NumberApprovedExpires (estimated)
United States58440992008-02-272020-01-01
United States80802482008-02-272020-01-01
United States81143942008-02-272020-01-01
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
ATC CodesL04AC04
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelDownload (148 KB)
MSDSDownload (568 KB)
Interactions
Drug Interactions
Drug
AdalimumabAnti-TNF Agents may enhance the adverse/toxic effect of Rilonacept.
CanakinumabInterleukin-1 Inhibitors may enhance the adverse/toxic effect of Canakinumab. Whether such a combination will also alter the therapeutic response to one or both agents is unclear.
Certolizumab pegolAnti-TNF Agents may enhance the adverse/toxic effect of Rilonacept.
DenosumabMay enhance the adverse/toxic effect of Immunosuppressants. Specifically, the risk for serious infections may be increased.
EtanerceptAnti-TNF Agents may enhance the adverse/toxic effect of Rilonacept.
golimumabAnti-TNF Agents may enhance the adverse/toxic effect of Rilonacept.
InfliximabAnti-TNF Agents may enhance the adverse/toxic effect of Rilonacept.
LeflunomideImmunosuppressants may enhance the adverse/toxic effect of Leflunomide. Specifically, the risk for hematologic toxicity such as pancytopenia, agranulocytosis, and/or thrombocytopenia may be increased.
LenalidomideAnti-TNF Agents may enhance the adverse/toxic effect of Rilonacept.
NatalizumabImmunosuppressants may enhance the adverse/toxic effect of Natalizumab. Specifically, the risk of concurrent infection may be increased.
PimecrolimusMay enhance the adverse/toxic effect of Immunosuppressants.
PomalidomideAnti-TNF Agents may enhance the adverse/toxic effect of Rilonacept.
RoflumilastMay enhance the immunosuppressive effect of Immunosuppressants.
Sipuleucel-TImmunosuppressants may diminish the therapeutic effect of Sipuleucel-T.
ThalidomideAnti-TNF Agents may enhance the adverse/toxic effect of Rilonacept.
TofacitinibImmunosuppressants may enhance the immunosuppressive effect of Tofacitinib.
TrastuzumabMay enhance the neutropenic effect of Immunosuppressants.
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

Comments
comments powered by Disqus
Drug created on March 19, 2008 10:27 / Updated on August 06, 2013 15:43