Oclacitinib
[CAS# 1208319-26-9]

Identification

• Classification: API >> Other chemicals
• Name: Oclacitinib
• Synonyms: JAKi; PF 03394197; trans-N-Methyl-4-(methyl-7H-pyrrolo[2,3-d]pyrimidin-4-ylamino)-cyclohexanemethanesulfonamide
• Molecular Formula: C₁₅H₂₃N₅O₂S
• Molecular Weight: 337.44
• CAS Registry Number: 1208319-26-9
• EC Number: 950-980-7
• SMILES: CNS(=O)(=O)CC1CCC(CC1)N(C)C2=NC=NC3=C2C=CN3

Properties

• Solubility: Practically insoluble (0.034 g/L) (25 ºC), Calc.^*
• Density: 1.316±0.06 g/cm³ (20 ºC 760 Torr), Calc.^*
• Index of Refraction: 1.618, Calc.^*

^* Calculated using Advanced Chemistry Development (ACD/Labs) Software.

Safety Data

• Hazard Symbols: GHS07 Warning
• Hazard Statements: H302-H317
• Precautionary Statements: P280

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Acute toxicity	Acute Tox.	4	H302
Chronic hazardous to the aquatic environment	Aquatic Chronic	2	H411

Discovory and Applicatios

Oclacitinib is a synthetic compound developed as a selective Janus kinase (JAK) inhibitor for veterinary medicine, specifically targeting canine pruritus and atopic dermatitis. The discovery of oclacitinib stemmed from the need for a more targeted and rapid-acting treatment for allergic skin conditions in dogs. Traditionally, corticosteroids were the primary treatment option, but they often caused significant side effects with long-term use. Oclacitinib was designed to inhibit the JAK-STAT signaling pathway, which plays a critical role in the inflammatory response associated with allergic conditions.

The mechanism of oclacitinib involves the selective inhibition of JAK1, a key enzyme that mediates the signaling of pro-inflammatory cytokines such as interleukin-31 (IL-31). IL-31 is a significant driver of pruritus (itching) in dogs with atopic dermatitis. By blocking JAK1, oclacitinib effectively reduces the itch response and inflammation without broadly suppressing the immune system. This specificity allows for more precise control of symptoms while minimizing side effects compared to traditional immunosuppressants.

Oclacitinib was approved by the U.S. Food and Drug Administration (FDA) in 2013 under the brand name Apoquel for the treatment of canine pruritus and atopic dermatitis. Clinical trials demonstrated that oclacitinib provided rapid relief of itching, often within 24 hours of administration. Unlike corticosteroids, which can cause polyuria, polydipsia, and weight gain, oclacitinib’s targeted action resulted in fewer systemic side effects. Its oral administration and fast onset made it a preferred choice for managing chronic and acute flare-ups of allergic skin conditions in dogs.

The success of oclacitinib in veterinary dermatology is attributed to its ability to provide consistent and sustained relief of itching and inflammation. Studies have shown that dogs receiving oclacitinib experience significant improvement in skin lesions and overall quality of life. The drug's efficacy extends to various allergic conditions, including flea allergy dermatitis, food allergies, and contact dermatitis. This versatility has made it an essential tool in veterinary practice for managing diverse pruritic disorders.

Oclacitinib has also sparked interest in further research into JAK inhibitors for other inflammatory and immune-mediated diseases in animals. Its success has led to investigations into similar compounds for treating conditions like feline dermatitis and immune-mediated diseases in other species. Additionally, research into the long-term safety and efficacy of oclacitinib continues to expand, providing valuable data for optimizing its use in clinical practice.

While oclacitinib represents a significant advancement in veterinary dermatology, it is not without limitations. It is contraindicated in dogs less than 12 months old and in dogs with severe immunosuppression or neoplastic conditions. Careful monitoring during treatment is recommended to ensure safety, especially in long-term use.

The development of oclacitinib marks a milestone in veterinary medicine by offering a targeted, effective, and safer alternative to traditional therapies for allergic skin diseases. Its discovery has paved the way for more research into JAK inhibitors, promising new avenues for treating inflammatory and immune-mediated conditions in companion animals.