Interleukins are cell-signaling cytokines that are produced by a variety of cells, primarily T cells. Knowledge about their actions has improved the understanding of the pathogenesis of human diseases and provided potential drug targets for targeted therapy.
To date, these research achievements have been translated into clinical use. For example, Mepolizumab (brand name: Nucala) is approved by the U.S. Food and Drug Administration (FDA) in 2015 which is a humanized monoclonal antibody targeted interleukin 5 (IL-5). It's used for the treatment of severe eosinophilic asthma.
Since interleukins are important for targeted therapy, here we list most of its related drug target, drug name, clinical stage, drug type and manufacturing company.
|Drug target||Drug name||Clinical stage||Drug type||Company|
|IL1A, IL1B||Rilonacept||Approved||Human fusion protein||Regeneron Pharmaceutical|
|IL1B||Canakinumab||Approved||Human whole antibody||Novartis|
|IL1R1||Anakinra||Approved||IL-1 receptor antagonist||Amgen, SOBI|
|IL2RA||Daclizumab||Approved||Humanized whole antibody||Roche, Biogen, Abbvie|
|IL4R||Dupilumab||Approved||Human whole antibody||Sanofi, Regeneron Pharmaceutical|
|IL5||Mepolizumab||Approved||Humanized whole antibody||GlaxoSmithKline|
|IL5RA||Benralizumab||Phase III||Humanized whole antibody||Biowa, MedImmune|
|IL6||Siltuximab||Approved||Chimeric whole antibody||Janssen|
|IL6R||Tocilizumab||Approved||Humanized whole antibody||Chugai, Genentech|
|IL9||Enokizumab||Phase II Discontinued||Humanized whole antibody||Genaera, Ludwig Institute for
Cancer Research, MedImmune,
|IL12B||Ustekinumab||Approved||Human whole antibody||Janssen|
|IL13||Tralokinumab||Phase III||Human whole antibody||MedImmune, AstraZeneca|
|IL17A||Secukinumab||Approved||Human whole antibody||Novartis, Maruho Pharmaceutical|
|IL17RA||Brodalumab||Approved||Human whole antibody||Amegen, AstraZeneca,
Kyowa Hakko Kirin,
Valeant, Leo Pharma
|IL22||Fezakinumab||Phase II Discontinued||Whole antibody||Pfizer|
|IL23A||Tildrakizumab||BLA Filing||Humanized whole antibody||Merck Sharp & Dohme,
|IL31RA||Nemolizumab||Phase II||Humanized whole antibody||Chugai|
Interleukin 1 alpha (IL1A), also known as hematopoietin 1, is a cytokine of the interleukin 1 family which involves in various immune responses, inflammatory processes, and hematopoiesis. Rilonacept, an anti-IL1 targeted therapy, is used for familial chylomicronemia syndrome (FCS), cryopyrin-associated periodic syndromes (CAPS) and muckle-wells syndrome (MWS).
Interleukin 1 beta (IL1B), is a member of the interleukin 1 cytokine family which involves in a variety of cellular activities, including cell proliferation, differentiation, and apoptosis. Canakinumab, an anti-IL1B tageted therapy, is used for systemic juvenile idiopathic arthritis, cryopyrin-associated periodic syndromes (CAPS), tumor necrosis factor receptor associated periodic syndrome (TRAPS), hyperimmunoglobulin D syndrome and familial mediterranean fever.
Interleukin 1 receptor type 1 (IL1R1), belongs to the interleukin-1 receptor family which involves in many cytokine-induced immune and inflammatory responses.. It's a receptor for interleukin-1 alpha, interleukin-1 beta, and interleukin-1 receptor antagonist. Anakinra, an anti-IL1R1 targeted therapy, is used for rheumatoid arthritis (RA) and cryopyrin-associated periodic syndromes (CAPS).
Interleukin 2 receptor alpha chain (IL2RA), is a member of the common gamma-chain receptor family. Daclizumab, an anti-IL2RA targeted therapy, is used for rejection of organ transplantation and multiple sclerosis (MS).
Interleukin 4 receptor (IL4R), binds interleukin 4 and interleukin 13 to regulate IgE antibody production. It also binds interleukin 4 to promote differentiation of Th2 cells. Dupilumab, an anti-IL4R targeted therapy, is used for atopic dermatitis.
Interleukin 5 (IL5), is a member of the common beta-chain receptor family which involoves in the regulation of eosinophil formation, maturation, recruitment and survival. Mepolizumab, an anti-IL5 targeted therapy, is used for asthma.
Interleukin 5 receptor alpha chain (IL5RA), also known as CD125, is a member of the common beta-chain receptor family. Benralizumab, an anti-IL5RA targeted therapy, is still under clinical phase III trial which is used for chronic obstructive pulmonary disease (COPD), asthma and hypereosinophilic syndrome (HES).
Interleukin 6 (IL6), acts as both a pro-inflammatory cytokine and an anti-inflammatory cytokine. Siltuximab, an anti-IL6 targeted therapy, is used for multicentric castleman's disease (MCD).
Interleukin 6 receptor (IL6R), also known as CD126, is a subunit of the interleukin 6 (IL6) receptor complex. Tocilizumab, an anti-IL6R targeted therapy, is used for rheumatoid arthritis (RA), juvenile rheumatoid arthritis (JRA) and multicentric castleman's disease (MCD).
Interleukin 9 (IL9), is a cytokine secreted by CD4+ helper cells that acts as a regulator of a variety of hematopoietic cells. Enokizumab, an anti-IL9 targeted therapy, was designed to treat asthma but failed in clinical phase II trials.
Interleukin 12 beta subunit (IL12B), also known as IL12 p40 subunit, is a common subunit of interleukin 12 and interleukin 23. Ustekinumab, an anti-IL12B targeted therapy, is used for plaque psoriasis, active psoriatic arthritis and Crohn's disease.
Interleukin 13 (IL13), is involved in several stages of B-cell maturation and differentiation. Tralokinumab, an anti-IL13 targeted therapy, is still under clinical phase III trial which is used for asthma, idiopathic pulmonary fibrosis (IPF) and atopic dermatitis.
Interleukin 17A (IL17A), is a proinflammatory cytokine produced by activated T cells which can stimulate the expression of IL6 and cyclooxygenase-2 (PTGS2/COX-2), as well as enhance the production of nitric oxide (NO). Secukinumab, an anti-IL17A targeted therapy, is used for psoriasis, psoriatic arthritis and ankylosing spondylitis (AS).
Interleukin 17 receptor A (IL17RA), also known as CDw217, is a member of interleukin 17 (IL-17) family. Brodalumab, an anti-IL17RA targeted therapy, is used for psoriasis vulgaris, psoriatic arthritis, psoriatic erythroderma, pustular psoriasis and plaque psoriasis.
Interleukin 22 (IL22), is a member of interleukin 10 (IL10) family which binds to a heterodimeric cell surface receptor composed of IL-10R2 and IL-22R1 subunits. Fezakinumab, an anti-IL22 targeted therapy, was designed to treat rheumatoid arthritis (RA)but failed in clinical phase II trials.
Interleukin 23 alpha subunit (IL23A), associates with IL12B to form the IL-23 interleukin, a heterodimeric cytokine which functions in innate and adaptive immunity. Tildrakizumab, an anti-IL23A targeted therapy, is under Biologics License Application (BLA) filling. This drug is uesd for treament of plaque psoriasis.
Interleukin-31 receptor A (IL31RA), functions either as a monomer, or as part of a receptor complex with oncostatin M receptor (OSMR). Nemolizumab, an anti-IL23A targeted therapy, is still under clinical phase III trial which is used for atopic dermatitis and pruritus.
the information above was updated by 2017.7