Repositioning Candidate Details
| Candidate ID: | R1437 |
| Source ID: | DB12169 |
| Source Type: | approved; investigational |
| Compound Type: | biotech |
| Compound Name: | Tralokinumab |
| Synonyms: | Tralokinumab |
| Molecular Formula: | -- |
| SMILES: | -- |
| DrugBank Description: | Atopic dermatitis (AD) is an inflammatory skin disorder that causes skin inflammation, skin barrier dysfunction, and chronic pruritus. It is estimated to affect up to 20% of adults and children worldwide, and is frequently associated with other atopic conditions such as asthma or allergic rhinitis. While AD is a heterogenous condition with a variety of apparent genetic and environmental causes, it is primarily driven by the pro-inflammatory cytokine interleukin-13 (IL-13). Tralokinumab is a fully human IgG4 monoclonal antibody targeted against IL-13. It neutralizes IL-13 activity by inhibiting its ability to bind with receptors, thus helping to alleviate AD symptoms. Tralokinumab was first approved for the treatment of atopic dermatitis by the EMA in June 2021, under the brand name Adtralza (Leo Pharma), and was subsequently approved in Canada in October 2021. |
| CAS Number: | 1044515-88-9 |
| Molecular Weight: | |
| DrugBank Indication: | Tralokinumab is indicated in Canada and the EU for the treatment of adult patients with moderate-to-severe atopic dermatitis who are candidates for systemic therapy and are inadequately controlled with topical interventions. |
| DrugBank Pharmacology: | Tralokinumab exerts its therapeutic effects by inhibiting the inflammatory cytokine (IL-13) primarily responsible for the pathogenesis of atopic dermatitis. It is administered subcutaneously with a loading dose of 600mg followed by a maintenance dose of 300mg every two weeks. In clinical studies, tralokinumab treatment decreased the concentrations of a number of Th2 and Th22 immunity biomarkers in the blood, including periostin, IL-22, serum IgE. It also reduced epidermal thickness and decreased the expression of Keratin 16 and Ki-67 in skin affected by atopic dermatitis. Hypersensitivity reactions, including anaphylaxis, have been reported following the use of tralokinumab. Patients experiencing a systemic hypersensitivity reaction should discontinue treatment and initiate immediate therapy as clinically indicated. Tralokinumab should not be used in patients with pre-existing helminth infections, as the influence of tralokinumab on the immune response against helminth infections is unclear. Patients with helminth infections should be treated prior to therapy with tralokinumab. Patients becoming infected during the course of therapy may be treated with anti-helminth medications, but should discontinue tralokinumab if the infection fails to resolve. |
| DrugBank MoA: | Interleukin-13 (IL-13) is a pro-inflammatory cytokine that has been implicated as the primary driver of atopic dermatitis (AD). IL-13 binds with high affinity to both a heterodimeric form of IL-13Rα1 - complexed with IL-4Rα - and to IL-13Rα2, both of which are expressed on keratinocytes and fibroblasts. While IL-13Rα2 does not appear to act as a signal mediator, the binding of IL-13 to heterodimeric IL-4Rα and IL-13Rα1 activates downstream Janus kinase 2 (JAK2) and tyrosine kinase 2 (TYK2) pathways which proceed to activate various signal transducer and activator of transcription (STAT) pathways. STAT signalling induces the expression of periostin, an extracellular matrix protein which serves a number of physiological functions in addition to its pathogenic role in skin fibrosis and chronic allergic inflammation. IL-13 also appears to contribute to skin barrier dysfunction via an indirect downregulation of filaggrin (FLG), a structural protein essential for correct skin barrier functioning. Tralokinumab is a monoclonal antibody targeted against IL-13. It neutralizes the activity of IL-13 by blocking its interaction with both the IL-13Rα1/IL-4Rα receptor complex and IL-13Rα2 receptors. |
| Targets: | Interleukin-13 antibody |
| Inclusion Criteria: | Therapeutic strategy associated |
| Strategy ID | Strategy | Synonyms | Related Targets | Related Drugs | |
|---|---|---|---|---|---|
| S03 | Anti-fibrosis | fibrosis | Angiotensin Receptor Blocker (ARB); CCR2/CCR5 antagonist; Thyroid receptor β agonist; PEGylated human FGF21 analogue; Monoclonal antibody to lysyl oxidase-like 2 (LOXL2); Galectin-3 inhibitor; FGF19 variant | Losartan; Cenicriviroc; VK-2809; MGL-3196; Pegbelfermin; Simtuzumab; GR-MD-02; NGM282 | Details |
| S05 | Anti-inflammatory | inflammatory | Bile acid; TNF-a inhibitor; Dual PPAR-α and -δ agonists; Toll-Like Receptor; (TLR)-4 antagonist; Caspase inhibitor; ASK-1 inhibitor | Ursodeoxycholic Acid; Pentoxifylline; Elafibranor; JKB-121; Emricasan; Selonsertib; | Details |
| Diseases ID | DO ID | Disease Name | Definition | Class |
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