Deucravacitinib

Mechanism of Action

Tyrosine kinase 2 (TYK2) is a member of the Janus kinase (JAK) family of kinases, which are intracellular tyrosine kinases that activate the JAK–signal transducer and activator of the transcription pathway. Unlike other members of the JAK family that promote broader immune and extra-immune pathways, such as lipid metabolism, the TYK2 signalling pathway is responsible for selected immune pathways.1 TYK2 mediates the signalling of inflammatory cytokines of both adaptive (e.g., interleukin (IL) 12 and IL-23) and innate (e.g., type I interferons) immune responses.3 IL-23 has been implicated in the pathogenesis of immune-mediated disorders such as psoriasis and psoriatic arthritis.1 It activates and promotes the proliferation of Th17 cells: subsequently, Th17 cells secrete inflammatory mediators, such as IL-17 and tumour necrosis factor-alpha, that stimulate epidermal cells to produce cytokines and chemokines that attract and activate innate immune system cells.1,2 Enhanced activity of Th17 cells leads to sustained inflammatory responses in the skin and joints as manifested in psoriatic arthritis.1

Deucravacitinib inhibits TYK2 via an allosteric mechanism: it binds to the enzyme's regulatory domain - also known as the pseudokinase (JH2) domain - instead of the catalytic domain. This binding activity allows high selectivity towards TYK2 over other tyrosine kinase enzymes. In in vitro cellular assays, deucravacitinib showed a 100-fold to 2000-fold selectivity for TYK2 over JAK 1/2/3 and demonstrated minimal or no activity against JAK 1/2/3. Upon binding to TYK2, deucravacitinib induces a conformational change and locks the regulatory domain of TYK2 into an inhibitory confirmation with the catalytic domain, trapping TYK2 in an inactive state.1,2 Inhibiting TYK2 leads to the downregulation of the IL-23/TH17 pathway, IL-12 signalling, type 1 interferon pathway, and keratinocyte activation

Indication

Deucravacitinib is a tyrosine kinase 2 (TYK2) inhibitor indicated for the treatment of adults with moderate-to-severe plaque psoriasis who are candidates for systemic therapy or phototherapy. It is not recommended for use in combination with other potent immunosuppressants

Dr. Reddy's Expertise

Headquartered in Hyderabad, India, Dr. Reddy's Laboratories is one of the leading Active Pharmaceutical Ingredients (API) manufacturers and suppliers globally for Deucravacitinib API. Dr. Reddy's API business is a preferred partner to pharma companies across the US, Europe, Brazil, Latin America, Japan, China, Korea, Middle East and other emerging markets.

Dr. Reddy's API business thrives on the deep technical strengths established over the last 30+ years in the development and manufacture of complex APIs such as steroids, peptides, complex long chain molecules and highly potent APIs (HPAPIs / oncology drugs). This expertise is complemented by our prowess in intellectual property and regulatory affairs which helps us consistently meet and exceed regulatory standards. Dr. Reddy's Deucravacitinib API is the outcome of the extensive expertise in R&D, IP, and Regulatory.

A key component in helping our customers be first to market is a responsive supply chain. We achieve this by making sure that all our facilities are operating efficiently and to the latest standards of quality, safety, and productivity. A strong interconnect between business and factories allows for a quick reaction to dynamic market changes, so that we can avert shortages and meet sudden surges in demand.