U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS
This repository is under review for potential modification in compliance with Administration directives.

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
Structure of RITLECITINIB MALONATE

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

HIDE SMILES / InChI

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

TargetsConditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
LITFULO

Approved Use

LITFULO is a kinase inhibitor indicated for the treatment of severe alopecia areata in adults and adolescents 12 years and older.

Launch Date

2023
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
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

AUC

ValueDoseCo-administeredAnalytePopulation
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

T1/2

ValueDoseCo-administeredAnalytePopulation
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

Funbound

ValueDoseCo-administeredAnalytePopulation
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

Overview

Drug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
no
no
no
no
no
no
no
no
no
no
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.
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.
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.
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.
Page: 67.0
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 victimTox targets

Tox targets

PubMed

PubMed

TitleDatePubMed
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
Patents

Sample Use Guides

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
Created
by admin
on Mon Mar 31 22:28:17 GMT 2025
Edited
by admin
on Mon Mar 31 22:28:17 GMT 2025
Record UNII
132LF5WGH4
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
RITLECITINIB MALONATE
Common Name English
PF-06651600 MALONATE
Preferred Name English
1-((2S,5R)-2-METHYL-5-(7H-PYRROLO(2,3-D)PYRIMIDIN-4-YLAMINO)-1-PIPERIDINYL)-2-PROPEN-1-ONE MALONATE
Systematic Name English
PROPANEDIOIC ACID, COMPD. WITH 1-((2S,5R)-2-METHYL-5-(7H-PYRROLO(2,3-D)PYRIMIDIN-4-YLAMINO)-1-PIPERIDINYL)-2-PROPEN-1-ONE (1:1)
Systematic Name English
Code System Code Type Description
PUBCHEM
124203830
Created by admin on Mon Mar 31 22:28:17 GMT 2025 , Edited by admin on Mon Mar 31 22:28:17 GMT 2025
PRIMARY
FDA UNII
132LF5WGH4
Created by admin on Mon Mar 31 22:28:17 GMT 2025 , Edited by admin on Mon Mar 31 22:28:17 GMT 2025
PRIMARY
CAS
2140301-97-7
Created by admin on Mon Mar 31 22:28:17 GMT 2025 , Edited by admin on Mon Mar 31 22:28:17 GMT 2025
PRIMARY
SMS_ID
300000045439
Created by admin on Mon Mar 31 22:28:17 GMT 2025 , Edited by admin on Mon Mar 31 22:28:17 GMT 2025
PRIMARY
Related Record Type Details
PARENT -> SALT/SOLVATE
Related Record Type Details
ACTIVE MOIETY