Details
Stereochemistry | ABSOLUTE |
Molecular Formula | C15H19N5O.C3H4O4 |
Molecular Weight | 389.4057 |
Optical Activity | UNSPECIFIED |
Defined Stereocenters | 2 / 2 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
OC(=O)CC(O)=O.C[C@H]1CC[C@H](CN1C(=O)C=C)NC2=NC=NC3=C2C=CN3
InChI
InChIKey=QMPMPSGDPRHZCG-VZXYPILPSA-N
InChI=1S/C15H19N5O.C3H4O4/c1-3-13(21)20-8-11(5-4-10(20)2)19-15-12-6-7-16-14(12)17-9-18-15;4-2(5)1-3(6)7/h3,6-7,9-11H,1,4-5,8H2,2H3,(H2,16,17,18,19);1H2,(H,4,5)(H,6,7)/t10-,11+;/m0./s1
Molecular Formula | C15H19N5O |
Molecular Weight | 285.3443 |
Charge | 0 |
Count |
|
Stereochemistry | ABSOLUTE |
Additional Stereochemistry | No |
Defined Stereocenters | 2 / 2 |
E/Z Centers | 0 |
Optical Activity | UNSPECIFIED |
Molecular Formula | C3H4O4 |
Molecular Weight | 104.0615 |
Charge | 0 |
Count |
|
Stereochemistry | ACHIRAL |
Additional Stereochemistry | No |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 0 |
Optical Activity | NONE |
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 Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: CHEMBL2148 |
33.1 nM [IC50] |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Primary | LITFULO Approved UseLITFULO is a kinase inhibitor indicated for the treatment of severe alopecia areata in adults and adolescents 12 years and older. Launch Date2023 |
Cmax
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
186.9 ng/mL |
30 mg 1 times / day steady-state, oral dose: 30 mg route of administration: Oral experiment type: STEADY-STATE co-administered: |
RITLECITINIB plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
|
194.3 ng/mL |
30 mg 1 times / day steady-state, oral dose: 30 mg route of administration: Oral experiment type: STEADY-STATE co-administered: |
RITLECITINIB plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
|
445.6 ng/mL |
50 mg 1 times / day steady-state, oral dose: 50 mg route of administration: Oral experiment type: STEADY-STATE co-administered: |
RITLECITINIB plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
AUC
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
383.6 ng × h/mL |
30 mg 1 times / day steady-state, oral dose: 30 mg route of administration: Oral experiment type: STEADY-STATE co-administered: |
RITLECITINIB plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
|
454.5 ng × h/mL |
30 mg 1 times / day steady-state, oral dose: 30 mg route of administration: Oral experiment type: STEADY-STATE co-administered: |
RITLECITINIB plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
|
986.3 ng × h/mL |
50 mg 1 times / day steady-state, oral dose: 50 mg route of administration: Oral experiment type: STEADY-STATE co-administered: |
RITLECITINIB plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
T1/2
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
2 h |
30 mg 1 times / day steady-state, oral dose: 30 mg route of administration: Oral experiment type: STEADY-STATE co-administered: |
RITLECITINIB plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
|
2.3 h |
100 mg 1 times / day steady-state, oral dose: 100 mg route of administration: Oral experiment type: STEADY-STATE co-administered: |
RITLECITINIB plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: |
Funbound
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
86% |
100 mg 1 times / day steady-state, oral dose: 100 mg route of administration: Oral experiment type: STEADY-STATE co-administered: |
RITLECITINIB plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: |
Overview
CYP3A4 | CYP2C9 | CYP2D6 | hERG |
---|---|---|---|
Drug as perpetrator
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
Page: 16.0 |
no | |||
Page: 16.0 |
no | |||
Page: 16.0 |
no | |||
Page: 16.0 |
no | |||
Page: 16.0 |
no | |||
Page: 16.0 |
no | |||
Page: 16.0 |
no | |||
Page: 16.0 |
no | |||
Page: 16.0 |
no | |||
Page: 16.0 |
no | |||
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2023/215830Orig1s000MultidisciplineR.pdf Page: 67.0 |
no | no (co-administration study) Comment: no clinically relevant change in the systemic exposure of rosuvastatin which is a substrate of OATP1B1, BCRP, and OAT3 was observed. Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2023/215830Orig1s000MultidisciplineR.pdf Page: 67.0 |
||
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2023/215830Orig1s000MultidisciplineR.pdf Page: 67.0 |
no | no (co-administration study) Comment: no clinically relevant change in the systemic exposure of rosuvastatin which is a substrate of OATP1B1, BCRP, and OAT3 was observed. Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2023/215830Orig1s000MultidisciplineR.pdf Page: 67.0 |
||
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2023/215830Orig1s000MultidisciplineR.pdf Page: 67.0 |
no | no (co-administration study) Comment: no clinically relevant change in the systemic exposure of rosuvastatin which is a substrate of OATP1B1, BCRP, and OAT3 was observed. Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2023/215830Orig1s000MultidisciplineR.pdf Page: 67.0 |
||
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2023/215830Orig1s000MultidisciplineR.pdf Page: 67.0 |
yes | yes (co-administration study) Comment: Caffeine (CYP1A2 substrate) AUC0-inf increased 2.7fold and Cmax 1.1fold following concomitant use with multiple doses of 200 mg ritlecitinib QD. Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2023/215830Orig1s000MultidisciplineR.pdf Page: 67.0 |
||
Page: 10 | 16 |
yes | yes (co-administration study) Comment: Ritlecitinib increased midazolam Cmax by 1.81-fold and AUCinf by 2.69-fold. Page: 10 | 16 |
Drug as victim
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
Page: 14 | 16 |
yes | |||
Page: 14.0 |
yes | |||
Page: 14.0 |
yes | |||
Page: 14.0 |
yes | |||
Page: 14.0 |
yes | |||
Page: 14.0 |
yes | |||
Page: 14.0 |
yes | |||
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2023/215830Orig1s000MultidisciplineR.pdf Page: 67.0 |
yes | yes (co-administration study) Comment: Rifampin (strong CYP3A inducer) decreased AUCinf and Cmax of ritlecitinib 50 mg dose by 0.44 and 0.25 fold. Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2023/215830Orig1s000MultidisciplineR.pdf Page: 67.0 |
Tox targets
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2023/215830Orig1s000MultidisciplineR.pdf Page: 44.0 |
PubMed
Title | Date | PubMed |
---|---|---|
A phase 2a randomized, placebo-controlled study to evaluate the efficacy and safety of the oral Janus kinase inhibitors ritlecitinib and brepocitinib in alopecia areata: 24-week results. | 2021 Aug |
|
Ritlecitinib: an investigational drug for the treatment of moderate to severe alopecia areata. | 2021 Dec |
|
Evaluating the Therapeutic Potential of Ritlecitinib for the Treatment of Alopecia Areata. | 2022 |
|
Efficacy and safety of ritlecitinib in adults and adolescents with alopecia areata: a randomised, double-blind, multicentre, phase 2b-3 trial. | 2023 May 6 |
|
A plain language summary on ritlecitinib treatment for adults and adolescents with alopecia areata. | 2023 Oct |
Sample Use Guides
In Vitro Use Guide
Sources: https://pubmed.ncbi.nlm.nih.gov/27791347
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
Created
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admin
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Edited
Mon Mar 31 22:28:17 GMT 2025
by
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Record UNII |
132LF5WGH4
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Record Status |
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Record Version |
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300000045439
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