Ritlecitinib

China [CN]

I. Basic Information

Item | Details

English Name | Ritlecitinib (PF-06651600), Tosylate: Ritlecitinib Tosylate

Chinese Name | 利特昔替尼 (Lìtèxītìní)

CAS Number | 2023795-59-0 (free base); 2241186-20-1 (p-toluenesulfonate)

Chemical Name | 1-{(2S,5R)-2-methyl-5-[(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]piperidin-1-yl}prop-2-en-1-one 4-methylbenzenesulfonate (1:1)

Molecular Formula | Free base C₁₆H₂₁N₅O; p-toluenesulfonate C₂₂H₂₇N₅O₄S

Molecular Weight | Free base 300.37; p-toluenesulfonate 457.55

Target | JAK3 (IC₅₀=0.16nM, irreversible inhibition); TEC family kinases (e.g., BTK, ITK, IC₅₀=0.5-2nM)

Developer | Pfizer

Market Launch | June 2023 (US FDA); September 2023 (EU); Application for market approval in China in 2024

Dosage Form and Strength | Capsules: 50mg/capsule (equivalent to 80.13mg Ritlecitinib tosylate)

II. Physicochemical Properties (Tosylate)

Parameter | Data

Appearance | White to off-white to light pink crystalline powder

Solubility | Freely soluble in water (>100mg/mL, 25℃), freely soluble in DMSO, soluble in methanol/ethanol

Dissociation Constant (pKa) | 7.8 (piperidine nitrogen), 9.1 (pyrrolo[2,3-d]pyrimidine nitrogen) (predicted value)

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

Chiral Characteristics: Contains 2 chiral centers (2S,5R configuration), optical purity >99.5%

Partition Coefficient (logP): 3.1 (free base); 1.8 (tosylate, predicted value)

Melting Point: 185-190℃ (decomposition, tosylate)

III. Mechanism of Action (Core Advantages)

Dual-channel irreversible inhibition: Covalently binds to the ATP binding sites of JAK3 and TEC family kinases, blocking JAK3-dependent cytokines such as IL-2, IL-7, and IL-15, and TEC-mediated immune receptor signaling, reducing CD8⁺T cell infiltration around hair follicles and relieving the immune attack on hair follicles.

Rapid hair regeneration: After 24 weeks of treatment, the response rate for SALT≤20 (hair loss ≤20%) reaches 55%-60%, and patients with alopecia totalis/universalis also show significant improvement.

High selectivity: Weak inhibitory activity against JAK1/2/TYK2 (IC₅₀>100nM), with lower off-target risks such as infection and anemia compared to pan-JAK inhibitors.

Convenient oral administration: Once daily, unaffected by food intake, with a bioavailability of approximately 75%, resulting in high patient compliance.