DT-Web

DB06372 - Rilonacept


Identification
Name Rilonacept
Accession Number DB06372
Type biotech
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.
Structure
MOL SDF PDB SMILES InChI
Categories (*)
Molecular Weight 251 kDa
Groups approved
Monoisotopic Weight Not Available
Pharmacology
Indication Rilonacept 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.
Mechanism of action CAPS 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-1?). Mutations in NLRP-3 result in an overactive inflammasome resulting in excessive release of activated IL-1? that drives inflammation. Rilonacept blocks IL-1? signaling by acting as a soluble decoy receptor that binds IL-1? and prevents its interaction with cell surface receptors. Rilonacept also binds IL-1? 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.
Absorption Not Available
Protein binding Not Available
Biotransformation Not Available
Route of elimination Not Available
Toxicity Not Available
Affected organisms
  • Humans and other mammals
Interactions
Drug Interactions
Drug Mechanism of interaction
Adalimumab results in increased immunosuppressive effects; increases the risk of infection.
Alefacept results in increased immunosuppressive effects; increases the risk of infection.
Anakinra results in increased immunosuppressive effects; increases the risk of infection.
Antithymocyte globulin results in increased immunosuppressive effects; increases the risk of infection.
APC8015 decreases effectiveness of APC8015 by pharmacodynamic antagonism.
Azathioprine results in increased immunosuppressive effects; increases the risk of infection.
Basiliximab results in increased immunosuppressive effects; increases the risk of infection.
Belatacept Belatacept 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.
Belatacept Belatacept 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.
Belatacept Belatacept 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.
Canakinumab results in increased immunosuppressive effects; increases the risk of infection.
Cyclosporine results in increased immunosuppressive effects; increases the risk of infection.
Daclizumab results in increased immunosuppressive effects; increases the risk of infection.
Denileukin diftitox decreases effects of toxoids by pharmacodynamic antagonism.
Denosumab Use caution with patients on concomitant immunosuppressants or those with compromised immune systems; increased risk of serious infection.
Efalizumab results in increased immunosuppressive effects; increases the risk of infection.
Etanercept results in increased immunosuppressive effects; increases the risk of infection.
Everolimus results in increased immunosuppressive effects; increases the risk of infection.
Glatiramer Acetate results in increased immunosuppressive effects; increases the risk of infection.
golimumab results in increased immunosuppressive effects; increases the risk of infection.
golimumab Avoid combination due to the enhancement of rilonacept associated side effects.
Hydroxychloroquine results in increased immunosuppressive effects; increases the risk of infection.
Infliximab results in increased immunosuppressive effects; increases the risk of infection.
Leflunomide results in increased immunosuppressive effects; increases the risk of infection.
Methotrexate Rilonacept and methotrexate both increase immunosuppressive effects; combination may increase risk of myelosuppression.
Muromonab results in increased immunosuppressive effects; increases the risk of infection.
Mycophenolate mofetil results in increased immunosuppressive effects; increases the risk of infection.
Sirolimus results in increased immunosuppressive effects; increases the risk of infection.
Tacrolimus results in increased immunosuppressive effects; increases the risk of infection.
Temsirolimus results in increased immunosuppressive effects; increases the risk of infection.
Thalidomide Thalidomide may increase the adverse effects of Rilonacept. Increased risk of serious infection. Concomitant therapy should be avoided.
Tocilizumab results in increased immunosuppressive effects; increases the risk of infection.
Trastuzumab Trastuzumab may increase the risk of neutropenia and anemia. Monitor closely for signs and symptoms of adverse events.
Food Interactions Not Available

Targets


Interleukin-1 beta
Name Interleukin-1 beta
Gene Name IL1B
Pharmacological action unknown
Actions binder
References
  • 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
  • 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
DTHybrid score 1.0727
Interleukin-1 alpha
Name Interleukin-1 alpha
Gene Name Not Available
Pharmacological action unknown
Actions binder
References
  • 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
  • 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
DTHybrid score Not Available
Interleukin-1 receptor antagonist protein
Name Interleukin-1 receptor antagonist protein
Gene Name Not Available
Pharmacological action unknown
Actions binder
References
  • 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
  • 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
DTHybrid score Not Available

Predictions


Id Partner name Gene Name Score
5142 Protein-tyrosine-phosphatase PPI 0.084
6315 V-type proton ATPase subunit B, brain isoform ATP6V1B2 0.0737
4218 Ribonucleoside-diphosphate reductase M2 subunit RRM2 0.0692
566 Serotransferrin TF 0.062
798 Osteocalcin BGLAP 0.061
494 Caspase-1 CASP1 0.0296
1507 Cytochrome c CYCS 0.0269
22 30S ribosomal protein S4 rpsD 0.0266
6714 30S ribosomal protein S4 rpsD 0.0266
183 Vascular endothelial growth factor A VEGFA 0.0251
140 30S ribosomal protein S9 rpsI 0.0251
6719 30S ribosomal protein S9 rpsI 0.0251
6725 30S ribosomal protein S9 rpsI 0.0251
2077 Caspase-3 CASP3 0.0248
65 Matrix metalloproteinase-9 Not Available 0.0242
275 Arachidonate 5-lipoxygenase ALOX5 0.0213
1024 Solute carrier family 22 member 11 SLC22A11 0.0174
6143 Solute carrier family 22 member 7 SLC22A7 0.0172
6142 Solute carrier family 22 member 8 SLC22A8 0.0151
1729 Solute carrier family 22 member 6 SLC22A6 0.0138
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