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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
Related Articles
Protein chemical formulaC9030H13932N2400O2670S74
Protein average weight251000.0 Da
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
Arcalyst
interleukin-1 (IL-1) trap
External Identifiers Not Available
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Arcalystinjection, powder, lyophilized, for solution160 mg/2mLsubcutaneousRegeneron Pharmaceuticals, Inc.2008-02-27Not applicableUs
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International BrandsNot Available
Brand mixturesNot Available
SaltsNot Available
CategoriesNot Available
UNII8K80YB5GMG
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.
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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
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US5844099 No2008-02-272020-01-01Us
US8080248 No2008-02-272020-01-01Us
US8114394 No2008-02-272020-01-01Us
Properties
StateSolid
Experimental PropertiesNot Available
References
Synthesis Reference

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

General References
  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:23031624 ]
  2. Tran TH, Pham JT, Shafeeq H, Manigault KR, Arya V: Role of interleukin-1 inhibitors in the management of gout. Pharmacotherapy. 2013 Jul;33(7):744-53. doi: 10.1002/phar.1265. Epub 2013 Apr 3. [PubMed:23553601 ]
  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:12815153 ]
  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:23319019 ]
External Links
ATC CodesL04AC04
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelDownload (148 KB)
MSDSDownload (568 KB)
Interactions
Drug Interactions
Drug
AdalimumabThe risk or severity of adverse effects can be increased when Adalimumab is combined with Rilonacept.
CanakinumabThe risk or severity of adverse effects can be increased when Rilonacept is combined with Canakinumab.
Certolizumab pegolThe risk or severity of adverse effects can be increased when Certolizumab pegol is combined with Rilonacept.
DenosumabThe risk or severity of adverse effects can be increased when Denosumab is combined with Rilonacept.
EtanerceptThe risk or severity of adverse effects can be increased when Etanercept is combined with Rilonacept.
golimumabThe risk or severity of adverse effects can be increased when golimumab is combined with Rilonacept.
InfliximabThe risk or severity of adverse effects can be increased when Infliximab is combined with Rilonacept.
LeflunomideThe risk or severity of adverse effects can be increased when Rilonacept is combined with Leflunomide.
LenalidomideThe risk or severity of adverse effects can be increased when Lenalidomide is combined with Rilonacept.
NatalizumabThe risk or severity of adverse effects can be increased when Rilonacept is combined with Natalizumab.
PimecrolimusThe risk or severity of adverse effects can be increased when Pimecrolimus is combined with Rilonacept.
PomalidomideThe risk or severity of adverse effects can be increased when Pomalidomide is combined with Rilonacept.
RoflumilastRoflumilast may increase the immunosuppressive activities of Rilonacept.
Sipuleucel-TThe therapeutic efficacy of Sipuleucel-T can be decreased when used in combination with Rilonacept.
TacrolimusThe risk or severity of adverse effects can be increased when Tacrolimus is combined with Rilonacept.
ThalidomideThe risk or severity of adverse effects can be increased when Thalidomide is combined with Rilonacept.
TofacitinibRilonacept may increase the immunosuppressive activities of Tofacitinib.
TrastuzumabTrastuzumab may increase the neutropenic activities of Rilonacept.
Food InteractionsNot Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
binder
General Function:
Protein domain specific binding
Specific Function:
Potent proinflammatory cytokine. Initially discovered as the major endogenous pyrogen, induces prostaglandin synthesis, neutrophil influx and activation, T-cell activation and cytokine production, B-cell activation and antibody production, and fibroblast proliferation and collagen production. Promotes Th17 differentiation of T-cells.
Gene Name:
IL1B
Uniprot ID:
P01584
Molecular Weight:
30747.7 Da
References
  1. Tran TH, Pham JT, Shafeeq H, Manigault KR, Arya V: Role of interleukin-1 inhibitors in the management of gout. Pharmacotherapy. 2013 Jul;33(7):744-53. doi: 10.1002/phar.1265. Epub 2013 Apr 3. [PubMed:23553601 ]
  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:23319019 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
binder
General Function:
Cytokine activity
Specific Function:
Produced by activated macrophages, IL-1 stimulates thymocyte proliferation by inducing IL-2 release, B-cell maturation and proliferation, and fibroblast growth factor activity. IL-1 proteins are involved in the inflammatory response, being identified as endogenous pyrogens, and are reported to stimulate the release of prostaglandin and collagenase from synovial cells.
Gene Name:
IL1A
Uniprot ID:
P01583
Molecular Weight:
30606.29 Da
References
  1. Tran TH, Pham JT, Shafeeq H, Manigault KR, Arya V: Role of interleukin-1 inhibitors in the management of gout. Pharmacotherapy. 2013 Jul;33(7):744-53. doi: 10.1002/phar.1265. Epub 2013 Apr 3. [PubMed:23553601 ]
  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:23319019 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
binder
General Function:
Interleukin-1, type ii receptor binding
Specific Function:
Inhibits the activity of interleukin-1 by binding to receptor IL1R1 and preventing its association with the coreceptor IL1RAP for signaling. Has no interleukin-1 like activity. Binds functional interleukin-1 receptor IL1R1 with greater affinity than decoy receptor IL1R2; however, the physiological relevance of the latter association is unsure.
Gene Name:
IL1RN
Uniprot ID:
P18510
Molecular Weight:
20054.82 Da
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:12815153 ]
  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:23319019 ]
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Drug created on March 19, 2008 10:27 / Updated on August 17, 2016 12:24