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
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
| 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 |
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 plain language summary on ritlecitinib treatment for adults and adolescents with alopecia areata. | 2023-10 |
|
| Efficacy and safety of ritlecitinib in adults and adolescents with alopecia areata: a randomised, double-blind, multicentre, phase 2b-3 trial. | 2023-05-06 |
|
| Evaluating the Therapeutic Potential of Ritlecitinib for the Treatment of Alopecia Areata. | 2022 |
|
| Ritlecitinib: an investigational drug for the treatment of moderate to severe alopecia areata. | 2021-12 |
|
| 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. | 2021-08 |
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
by
admin
on
Edited
Wed Apr 02 09:29:22 GMT 2025
by
admin
on
Wed Apr 02 09:29:22 GMT 2025
|
| Record UNII |
2OYE00PC25
|
| Record Status |
Validated (UNII)
|
| Record Version |
|
-
Download
| Name | Type | Language | ||
|---|---|---|---|---|
|
Preferred Name | English | ||
|
Official Name | English | ||
|
Common Name | English | ||
|
Common Name | English | ||
|
Common Name | English |
| Code System | Code | Type | Description | ||
|---|---|---|---|---|---|
|
2OYE00PC25
Created by
admin on Wed Apr 02 09:29:22 GMT 2025 , Edited by admin on Wed Apr 02 09:29:22 GMT 2025
|
PRIMARY | |||
|
11170
Created by
admin on Wed Apr 02 09:29:22 GMT 2025 , Edited by admin on Wed Apr 02 09:29:22 GMT 2025
|
PRIMARY | |||
|
DB14924
Created by
admin on Wed Apr 02 09:29:22 GMT 2025 , Edited by admin on Wed Apr 02 09:29:22 GMT 2025
|
PRIMARY | |||
|
300000010803
Created by
admin on Wed Apr 02 09:29:22 GMT 2025 , Edited by admin on Wed Apr 02 09:29:22 GMT 2025
|
PRIMARY | |||
|
1792180-81-4
Created by
admin on Wed Apr 02 09:29:22 GMT 2025 , Edited by admin on Wed Apr 02 09:29:22 GMT 2025
|
PRIMARY | |||
|
2OYE00PC25
Created by
admin on Wed Apr 02 09:29:22 GMT 2025 , Edited by admin on Wed Apr 02 09:29:22 GMT 2025
|
PRIMARY | |||
|
C161783
Created by
admin on Wed Apr 02 09:29:22 GMT 2025 , Edited by admin on Wed Apr 02 09:29:22 GMT 2025
|
PRIMARY | |||
|
118115473
Created by
admin on Wed Apr 02 09:29:22 GMT 2025 , Edited by admin on Wed Apr 02 09:29:22 GMT 2025
|
PRIMARY |
| Related Record | Type | Details | ||
|---|---|---|---|---|
|
SALT/SOLVATE -> PARENT |
|
||
|
TARGET -> INHIBITOR |
JAK3-Selective Inhibition over pan-JAK or JAK1-Selective Inhibition
IRREVERSIBLE INHIBITOR
IC50
|
||
|
|
OFF TARGET->NON-INHIBITOR |
IC50
|
||
|
OFF-TARGET->NON-INHIBITOR |
IC50
|
||
|
TARGET -> INHIBITOR |
IRREVERSIBLE INHIBITOR
k(inactivation)
|
||
|
|
OFF-TARGET->NON-INHIBITOR |
IC50
|
||
|
|
TARGET -> INHIBITOR |
IRREVERSIBLE INHIBITOR
kinact/Ki
|
||
|
SALT/SOLVATE -> PARENT |
| Related Record | Type | Details | ||
|---|---|---|---|---|
|
|
ACTIVE MOIETY |
|