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Details

Stereochemistry ABSOLUTE
Molecular Formula C15H19N5O
Molecular Weight 285.3443
Optical Activity UNSPECIFIED
Defined Stereocenters 2 / 2
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of RITLECITINIB

SMILES

C[C@H]1CC[C@H](CN1C(=O)C=C)NC2=NC=NC3=C2C=CN3

InChI

InChIKey=CBRJPFGIXUFMTM-WDEREUQCSA-N
InChI=1S/C15H19N5O/c1-3-13(21)20-8-11(5-4-10(20)2)19-15-12-6-7-16-14(12)17-9-18-15/h3,6-7,9-11H,1,4-5,8H2,2H3,(H2,16,17,18,19)/t10-,11+/m0/s1

HIDE SMILES / InChI

Molecular Formula C15H19N5O
Molecular Weight 285.3443
Charge 0
Count
MOL RATIO 1 MOL RATIO (average)
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 2 / 2
E/Z Centers 0
Optical Activity UNSPECIFIED

Description

Ritlecitinib is an orally administered, covalent small-molecule selective dual inhibitor of JAK3 and the TEC kinase family. In vitro studies showed ritlecitinib covalently binds to JAK3 and is more than 10 000 times more potent against JAK3 than against JAK1, JAK2, and tyrosine kinase. Ritlecitinib also inhibits the five members of the TEC kinase family. Ritlecitinib irreversibly inhibits Janus kinase 3 (JAK3) and TEC kinase family by blocking the adenosine triphosphate (ATP) binding site. In cellular settings, ritlecitinib inhibits cytokine induced STAT phosphorylation mediated by JAK3-dependent receptors. Additionally, ritlecitinib inhibits signaling of immune receptors dependent on TEC kinase family members.The FDA has approved ritlecitinib (LITFULO; Pfizer Inc), a once daily oral treatment, for individuals aged 12 years and older with severe alopecia areata. This makes ritlecitinib, in the 50 mg dosage, the first and only treatment approved by the FDA for adolescents with severe alopecia areata. The approval was based on the results of the ALLEGRO phase 2b/3 trial (NCT03732807), which included 718 individuals who had 50% or more scalp hair loss measured by the Severity of Alopecia Tool. Investigators of the study evaluated the safety and efficacy of ritlecitinib at 118 different sites in 18 different countries. Regulatory applications for LITFULO in alopecia areata have been submitted to countries around the world for review, including China, the European Union, Japan, and the United Kingdom. The European Medicines Agency (EMA) has accepted the Marketing Authorization Application (MAA) for ritlecitinib with a decision anticipated in the third quarter of 2023. LITFULO is also being evaluated for vitiligo, Crohn’s disease, and ulcerative colitis.

Approval Year

Targets

Primary TargetPharmacologyConditionPotency
33.1 nM [IC50]

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
LITFULO

Cmax

ValueDoseCo-administeredAnalytePopulation
186.9 ng/mL
30 mg 1 times / day steady-state, oral
RITLECITINIB plasma
Homo sapiens
194.3 ng/mL
30 mg 1 times / day steady-state, oral
RITLECITINIB plasma
Homo sapiens
445.6 ng/mL
50 mg 1 times / day steady-state, oral
RITLECITINIB plasma
Homo sapiens

AUC

ValueDoseCo-administeredAnalytePopulation
383.6 ng × h/mL
30 mg 1 times / day steady-state, oral
RITLECITINIB plasma
Homo sapiens
454.5 ng × h/mL
30 mg 1 times / day steady-state, oral
RITLECITINIB plasma
Homo sapiens
986.3 ng × h/mL
50 mg 1 times / day steady-state, oral
RITLECITINIB plasma
Homo sapiens

T1/2

ValueDoseCo-administeredAnalytePopulation
2 h
30 mg 1 times / day steady-state, oral
RITLECITINIB plasma
Homo sapiens
2.3 h
100 mg 1 times / day steady-state, oral
RITLECITINIB plasma
Homo sapiens

Funbound

ValueDoseCo-administeredAnalytePopulation
86%
100 mg 1 times / day steady-state, oral
RITLECITINIB plasma
Homo sapiens

Drug as perpetrator​

Drug as victim

Tox targets

PubMed

Sample Use Guides

In Vivo Use Guide
Recommended dosage is 50 mg orally once daily.
Route of Administration: Oral
In Vitro Use Guide
In total lymphocytes in human whole blood, Ritlecitinib inhibits the phosphorylation of STAT5 elicited by IL-2, IL-4, IL-7, and IL-15 with IC50 values of 244, 340, 407, and 266 nM, respectively, and it inhibits the phosphorylation of STAT3 elicited by IL-21 with an IC50 of 355 nM.
Substance Class Chemical
Record UNII
2OYE00PC25
Record Status Validated (UNII)
Record Version