Abrocitinib

China [CN]

I. Basic Information

Item | Details

English Name | Abrocitinib (PF-04965842)

Chinese Name | Abrocitinib (Abrotinib)

CAS Number | 1622902-68-4 NCBI

Chemical Name | N-{(1S,3S)-3-[methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]cyclobutyl}propane-1-sulfonamide

Molecular Formula | C₁₄H₂₁N₅O₂S

Molecular Weight | 323.42

Target | JAK1 (IC₅₀=29nM); High selectivity for JAK2 (803nM), JAK3 (>10μM), TYK2 (1250nM)

Developer | Pfizer

Market Launch | September 2021 (UK/Japan); January 2022 (US FDA); April 2022 (China NMPA)

Dosage Form and Specifications | Film-coated tablets: 50mg, 100mg, 200mg/tablet

II. Physicochemical Properties

Parameter | Data

Appearance | White to off-white crystalline powder

Solubility | Slightly soluble in water (approximately 0.1mg/mL, 25℃), readily soluble in DMSO, soluble in methanol/ethanol

Dissociation Constant (pKa) | 9.2 (amino group), 7.8 (sulfonamide group) (predicted value)

Stability | Stable for 36 months at 25℃/60% RH, store in a sealed, cool, and dry place; avoid strong light and high temperature

Chiral Characteristics | Contains 2 chiral centers (1S,3S configuration), optical purity >99.5%

Partition Coefficient (logP) | 2.8 (predicted value)

III. Mechanism of Action (Core Advantage)

Highly selective JAK1 inhibition: Reversibly binds to the ATP binding site of JAK1, blocking the JAK1-STAT signaling pathway of key inflammatory factors such as IL-4, IL-13, and IL-31 in AD. Signal transduction modulation, reducing inflammatory cell infiltration and release of pruritus mediators (Pfizer Medical).

Rapid anti-inflammatory and anti-itch effects: Significant relief of itching on the first day of treatment, improvement of skin lesions within 2 weeks, and an EASI-75 response rate of 60%-70% within 4 weeks, superior to traditional immunosuppressants.

Low off-target side effects: Low inhibitory activity against JAK2 (hematopoiesis-related) and JAK3 (immune cell development), resulting in lower risk of anemia and infection compared to non-selective JAK inhibitors.

Convenient oral administration: Once-daily dosing, approximately 60% bioavailability, unaffected by food intake, leading to high patient compliance.