Ritlecitinib

Summary

Ritlecitinib (CHEMBL4085457) is an approved small-molecule EC 2.7.10.2 (non-specific protein-tyrosine kinase) inhibitor (ATC L04AF08) targeting JAK1 and JAK3; indicated across 13 conditions including alopecia areata and vitiligo.

At a glance

• Status: Approved (max clinical phase 4)
• Modality: Small molecule
• ATC class: L04AF08
• Targets: 2 (JAK1, JAK3)
• Indications: 13 conditions
• Clinical trials: 49
• Chemistry: 285.34 Da · C15H19N5O

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL4085457
Name	Ritlecitinib
Type	Small molecule
Max phase	4
FDA approved	yes
PubChem CID	118115473
ChEBI	CHEBI:229233
ATC	L04AF08
Molecular formula	C15H19N5O
Molecular weight	285.34
InChIKey	CBRJPFGIXUFMTM-WDEREUQCSA-N

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

IUPAC name: 1-[(2S,5R)-2-methyl-5-(7H-pyrrolo[2,3-d]pyrimidin-4-ylamino)piperidin-1-yl]prop-2-en-1-one

ChEBI definition: A pyrrolopyrimidine that is 7H-pyrrolo[2,3-d]pyrimidine substituted at position 4 by a [(3R,6S)-6-methyl-1-(prop-2-enoyl)piperidin-3-yl]amino group. It is a dual inhibitor of Janus kinase 3 and the TEC family of tyrosine kinases.

Pharmacological roles (ChEBI): EC 2.7.10.2 (non-specific protein-tyrosine kinase) inhibitor, antirheumatic drug, anti-inflammatory drug, immunosuppressive agent, dermatologic drug.

Also known as: Pf-06651600, PF-06651600, Ritlecitinib, RITLECITINIB, Ritlecitin

Parent form; salt/anhydrous children: CHEMBL5314649

Patent coverage: 278 distinct patent families (708 SureChEMBL compound mentions), from 3 matched compound structure(s). One matched structure accounts for 655 (93%) of the total. Mentions count patents naming the compound (not distinct inventions), so promiscuous / reference molecules inflate the mention figure — families are the dedup metric.

Targets

Targets

Primary targets (GtoPdb curated mechanism): the Cancer dependency column is the DepMap CRISPR fitness signal (% of screened cell lines dependent on the target).

Gene	Target	Action	pAffinity	Cancer dependency	UniProt
JAK1	Janus kinase 1	Inhibition	5.79	2.8%	P23458
JAK3	Janus kinase 3	Inhibition	9.52	0.6%	P52333

Broader ChEMBL bioactivity targets: 9 (assay-derived). Sample: Tyrosine-protein kinase JAK3, Tyrosine-protein kinase Blk, Tyrosine-protein kinase JAK1, Tyrosine-protein kinase ITK/TSK, Receptor tyrosine-protein kinase erbB-4, Cytoplasmic tyrosine-protein kinase BMX, Tyrosine-protein kinase Tec, Tyrosine-protein kinase TXK, Tyrosine-protein kinase BTK.

Bioactivity

ChEMBL activities: 38 potent at pChembl ≥ 5 of 42 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
JAK3	9.52	IC50	0.3	nM	CHEMBL_ACT_18020317
JAK3	9.52	IC50	0.3	nM	CHEMBL_ACT_18757651
JAK3	9.52	IC50	0.3	nM	CHEMBL_ACT_19453555
JAK3	9.52	IC50	0.3	nM	CHEMBL_ACT_27143801
JAK3	9.52	IC50	0.3	nM	CHEMBL_ACT_28499426
JAK3	9.46	IC50	0.35	nM	CHEMBL_ACT_18453034
JAK3	9.4	IC50	0.4	nM	CHEMBL_ACT_18957309
JAK3	8.64	IC50	2.3	nM	CHEMBL_ACT_24825057
ITK	7.57	Ki	26.9	nM	CHEMBL_ACT_18020384
JAK3	7.48	IC50	33	nM	CHEMBL_ACT_18020309
JAK3	7.48	IC50	33	nM	CHEMBL_ACT_18757709
JAK3	7.48	IC50	33	nM	CHEMBL_ACT_19143999
JAK3	7.48	IC50	33.1	nM	CHEMBL_ACT_19489424
JAK3	7.48	IC50	33	nM	CHEMBL_ACT_22813268
JAK3	7.48	IC50	33.1	nM	CHEMBL_ACT_24788513
JAK3	7.48	IC50	33	nM	CHEMBL_ACT_25555176
JAK3	7.48	IC50	33.1	nM	CHEMBL_ACT_25848308
JAK3	7.48	IC50	33.1	nM	CHEMBL_ACT_27143804
JAK3	7.48	IC50	33.1	nM	CHEMBL_ACT_28499429
JAK3	7.48	IC50	33	nM	CHEMBL_ACT_29122449
JAK3	7.48	IC50	33	nM	CHEMBL_ACT_29231729
JAK3	7.29	IC50	51	nM	CHEMBL_ACT_18020323
JAK3	7.05	IC50	90	nM	CHEMBL_ACT_18020396
JAK3	6.97	IC50	106	nM	CHEMBL_ACT_18020407
TXK	6.88	Ki	131	nM	CHEMBL_ACT_18020385
TEC	6.81	IC50	155	nM	CHEMBL_ACT_25555180
JAK3	6.71	IC50	197	nM	CHEMBL_ACT_18020331
TXK	6.71	IC50	193	nM	CHEMBL_ACT_18020399
JAK3	6.7	IC50	202	nM	CHEMBL_ACT_18957344
BMX	6.26	Ki	545	nM	CHEMBL_ACT_18020383

Target pathways

Aggregated over 2 target gene(s): JAK1, JAK3.

Top Reactome pathways

54 total, by targets touching each:

Pathway	Targets	Genes
Interleukin-7 signaling	2	JAK1, JAK3
Cytokine Signaling in Immune system	2	JAK1, JAK3
Signal Transduction	2	JAK1, JAK3
Disease	2	JAK1, JAK3
Immune System	2	JAK1, JAK3
Signaling by Interleukins	2	JAK1, JAK3
Interleukin-2 family signaling	2	JAK1, JAK3
Interleukin-3, Interleukin-5 and GM-CSF signaling	2	JAK1, JAK3
Infectious disease	2	JAK1, JAK3
RAF/MAP kinase cascade	2	JAK1, JAK3
MAPK family signaling cascades	2	JAK1, JAK3
MAPK1/MAPK3 signaling	2	JAK1, JAK3
Interleukin-4 and Interleukin-13 signaling	2	JAK1, JAK3
Interleukin-20 family signaling	2	JAK1, JAK3
Interleukin-15 signaling	2	JAK1, JAK3
Interleukin-9 signaling	2	JAK1, JAK3
Interleukin-2 signaling	2	JAK1, JAK3
Interleukin-21 signaling	2	JAK1, JAK3
Interleukin receptor SHC signaling	2	JAK1, JAK3
Potential therapeutics for SARS	2	JAK1, JAK3
SARS-CoV Infections	2	JAK1, JAK3
Viral Infection Pathways	2	JAK1, JAK3
Interleukin-6 signaling	1	JAK1
MAPK3 (ERK1) activation	1	JAK1
RAF-independent MAPK1/3 activation	1	JAK1
MAPK1 (ERK2) activation	1	JAK1
ISG15 antiviral mechanism	1	JAK1
Antimicrobial mechanism of IFN-stimulated genes	1	JAK1
Signaling by ALK	1	JAK3
Interleukin-12 family signaling	1	JAK1

Dominant GO biological processes

GO term	Targets
protein phosphorylation	2
cell surface receptor signaling pathway via JAK-STAT	2
cytokine-mediated signaling pathway	2
cell differentiation	2
intracellular signal transduction	2
interleukin-15-mediated signaling pathway	2
interleukin-4-mediated signaling pathway	2
interleukin-2-mediated signaling pathway	2
interleukin-7-mediated signaling pathway	2
interleukin-9-mediated signaling pathway	2
growth hormone receptor signaling pathway via JAK-STAT	2
regulation of cell-cell adhesion	2
positive regulation of homotypic cell-cell adhesion	1
interleukin-11-mediated signaling pathway	1
type III interferon-mediated signaling pathway	1

Indications & clinical

Indications

13 indications (0 at ChEMBL trial phase 4). Phase below is the highest clinical-trial phase recorded for this drug against each disease — not the molecule’s overall approval status (that is in the Summary).

Indication	Trial phase	MONDO	EFO
alopecia areata	3	MONDO:0005340	EFO:0004192
vitiligo	3	MONDO:0008661	EFO:0004208
Crohn disease	2	MONDO:0005011	EFO:0000384
rheumatoid arthritis	2	MONDO:0008383	EFO:0000685
ulcerative colitis	2	MONDO:0005101	EFO:0000729
celiac disease	2	MONDO:0005130	EFO:0001060
Sezary syndrome	2	MONDO:0017844	EFO:1000785
mycosis fungoides	2	MONDO:0009691	EFO:1001051
alopecia	2	MONDO:0004907	EFO:1002028
type 1 diabetes mellitus	2	MONDO:0005147	MONDO:0005147
keloid	2	MONDO:0005348	EFO:0004212
liver disorder	1	MONDO:0005154	EFO:0001421
kidney disorder	1	MONDO:0005240	EFO:0003086

Clinical trials

Total trials: 49.

Phase distribution

Phase	Trials
PHASE1	24
PHASE2	15
PHASE3	5
Not specified	5

Top trials by phase / activity

NCT	Phase	Status	Title
NCT06072183	PHASE3	ACTIVE_NOT_RECRUITING	A 104-Week Study of Ritlecitinib Oral Capsules in Adults With Nonsegmental Vitiligo (Active and Stable) Tranquillo 2
NCT06163326	PHASE3	ACTIVE_NOT_RECRUITING	A 52-Week Study to Learn About the Safety and Effects of Ritlecitinib in Participants With Nonsegmental Vitiligo
NCT06873945	PHASE3	ACTIVE_NOT_RECRUITING	A Study of 2 Doses of Ritlecitinib in People 12 Years of Age and Older With Alopecia Areata
NCT04006457	PHASE3	COMPLETED	Long-Term PF-06651600 for the Treatment of Alopecia Areata
NCT05583526	PHASE3	COMPLETED	A 52-Week Study of Ritlecitinib Oral Capsules in Adults and Adolescents With Nonsegmental Vitiligo (Active and Stable) Tranquillo
NCT05743244	PHASE2	ACTIVE_NOT_RECRUITING	Janus Kinase (JAK) Inhibitors to Preserve C-Peptide Production in New Onset Type 1 Diabetes (T1D)
NCT06373458	PHASE2	RECRUITING	Ritlecitinib in Patients With Keloids or Those Undergoing Keloidectomy
NCT07219615	PHASE2	RECRUITING	A Study to Learn About Ritlecitinib for the Potential Treatment of Chronic Spontaneous Urticaria in Adults.
NCT07228390	PHASE2	RECRUITING	A 16-Week Study to Learn About the Study Medicine Called Ritlecitinib in Adults With Long Lasting Painful Red Skin Lumps, Known by the Medical Term, Hidradenitis Suppurativa, or HS.
NCT02958865	PHASE2	COMPLETED	Study to Compare Oral PF-06651600, PF-06700841 and Placebo in Subjects With Moderate to Severe Ulcerative Colitis
NCT02969044	PHASE2	COMPLETED	Study To Assess The Efficacy And Safety Of Pf-06651600 In Subjects With Rheumatoid Arthritis With An Inadequate Response To Methotrexate
NCT02974868	PHASE2	COMPLETED	Study To Evaluate The Efficacy And Safety Profile Of PF-06651600 And PF-06700841 In Subjects With Alopecia Areata
NCT03395184	PHASE2	COMPLETED	Study To Evaluate The Efficacy And Safety Of Oral PF-06651600 And PF-06700841 In Subjects With Moderate To Severe Crohn’s Disease
NCT03715829	PHASE2	COMPLETED	A Phase 2b Study To Evaluate The Efficacy And Safety Profile Of PF-06651600 And PF-06700841 In Active Non-segmental Vitiligo Subjects
NCT04413617	PHASE2	COMPLETED	TO ASSESS THE EFFICACY AND SAFETY OF PF-06650833, PF-06651600, AND TOFACITINIB ALONE AND IN COMBINATION IN PARTICIPANTS WITH ACTIVE RHEUMATOID ARTHRITIS WITH AN INADEQUATE RESPONSE TO METHOTREXATE
NCT04517864	PHASE2	TERMINATED	PLACEBO-CONTROLLED SAFETY STUDY OF RITLECITINIB (PF-06651600) IN ADULTS WITH ALOPECIA AREATA
NCT05549934	PHASE2	COMPLETED	Ritlecitinib for Cicatricial Alopecia
NCT05636293	PHASE2	COMPLETED	Double Blind, Placebo-controlled Trial to Establish Safety and Efficacy of Ritlecitinib in Celiac Disease Patients in Remission
NCT05879458	PHASE2	TERMINATED	Ritlecitinib in CTCL
NCT06795373	PHASE2	WITHDRAWN	Ritlecitinib (PF-06651600) in Participants With Chronic Spontaneous Urticaria
NCT02684760	PHASE1	COMPLETED	Bioavailability Study Of PF-06651600 In Healthy Subjects
NCT03232905	PHASE1	COMPLETED	Safety and Pharmacokinetic Study of PF-06651600 in Japanese Healthy Volunteers
NCT03608241	PHASE1	COMPLETED	A STUDY TO ESTIMATE THE EFFECT OF PF-06651600 ON THE PHARMACOKINETICS (PK) OF ORAL CONTRACEPTIVE (OC)
NCT03762928	PHASE1	COMPLETED	ESTIMATION OF THE EFFECT OF MULTIPLE DOSE PF-06651600 ON THE PHARMACOKINETICS OF SINGLE DOSE MIDAZOLAM AND EFAVIRENZ
NCT03827668	PHASE1	COMPLETED	A DRUG-DRUG INTERACTION STUDY BETWEEN PF-06650833 AND PF-06651600 FOLLOWING MULTIPLE DOSES IN HEALTHY PARTICIPANTS
NCT03916393	PHASE1	COMPLETED	PF-06651600 Taste Study.
NCT03929510	PHASE1	COMPLETED	Study to Characterize Absorption, Distribution, Metabolism and Excretion of 14C PF-06651600 and to Evaluate the Absolute Oral Bioavailability and Fraction Absorbed of PF-06651600.
NCT04004663	PHASE1	COMPLETED	Bioavailability Study of PF-06651600 Formulations in Healthy Participants
NCT04016077	PHASE1	COMPLETED	A Study to Evaluate the Pharmacokinetics, Safety and Tolerability of PF-06651600 in Subjects With Hepatic Impairment and Healthy Volunteers
NCT04018274	PHASE1	COMPLETED	Effect of PF-06651600 on the Pharmacokinetics of Oral Contraceptive Steroids
NCT04037865	PHASE1	TERMINATED	A Renal Impairment Study for PF-06651600
NCT04092595	PHASE1	COMPLETED	A Study of PF-06651600 Effect on Rosuvastatin Pharmacokinetics in Healthy Participants
NCT04266509	PHASE1	COMPLETED	Study to Evaluate the Effect of Repeat-Dose Rifampin on the Pharmacokinetics (PK) of PF-06651600
NCT04355845	PHASE1	COMPLETED	A STUDY TO EVALUATE THE EFFECT OF PF-06651600 ON PHARMACOKINETICS OF SINGLE DOSE SUMATRIPTAN IN HEALTHY PARTICIPANTS.
NCT04390776	PHASE1	COMPLETED	Bioequivalence Study of PF-06651600 Capsules Relative to Tablets and Estimation of Food Effect on Capsules.
NCT04634565	PHASE1	COMPLETED	PHARMACOKINETIC CHARACTERIZATION OF PF-06651600 IN CHINESE ADULT PARTICIPANTS
NCT04655040	PHASE1	COMPLETED	Estimation of the Effect of Multiple Dose Ritlecitinib (PF-06651600) on the Pharmacokinetics of a Single Dose of Caffeine in Healthy Participants
NCT05040295	PHASE1	COMPLETED	A Single Dose Study To Test Two Pediatric Forms Of Ritlecitinib Compared With Adult Ritlecitinib In Healthy Adults
NCT05097716	PHASE1	COMPLETED	Study to Evaluate the Effect of Multiple-Dose Ritlecitinib on the Pharmacokinetics (PK) of Tolbutamide
NCT05128058	PHASE1	COMPLETED	A Target Occupancy Study With Ritlecitinib.

Clinical evidence (CIViC)

No CIViC predictive evidence (expected for non-precision-medicine drugs).

Pharmacology

Pharmacogenomics

No CPIC/DPWG dosing guideline or drug-level clinical/variant annotations in PharmGKB for this molecule.

Related molecules

Related molecules

Molecules sharing ≥1 of this drug’s curated primary targets, merged from two biobtree sources and ranked by shared-target count, then clinical phase: ChEMBL clinical-stage candidates (development phase ≥2) and PubChem drug-class bioactivity (approved / known drugs acting on the target). Deduplicated by drug name; the drug’s own salt forms are excluded. Note: for a drug with few primary targets a shared-target match can reflect off-target / promiscuous binding rather than the same therapeutic mechanism — the phase ordering surfaces bona-fide therapeutics first.

99 molecules share ≥1 primary target. Top 60 by shared-target count:

Molecule	Source	Status	Shared targets
CRIZOTINIB	ChEMBL + PubChem	Phase 4 (approved)	JAK1, JAK3
dacomitinib	ChEMBL + PubChem	Phase 4 (approved)	JAK1, JAK3
DEUCRAVACITINIB	ChEMBL + PubChem	Phase 4 (approved)	JAK1, JAK3
Pazopanib	ChEMBL + PubChem	Phase 4 (approved)	JAK1, JAK3
ABROCITINIB	ChEMBL	Phase 4 (approved)	JAK1, JAK3
BARICITINIB	ChEMBL	Phase 4 (approved)	JAK1, JAK3
CERITINIB	ChEMBL	Phase 4 (approved)	JAK1, JAK3
ENTRECTINIB	ChEMBL	Phase 4 (approved)	JAK1, JAK3
FEDRATINIB	ChEMBL	Phase 4 (approved)	JAK1, JAK3
FILGOTINIB	ChEMBL	Phase 4 (approved)	JAK1, JAK3
MIDOSTAURIN	ChEMBL	Phase 4 (approved)	JAK1, JAK3
MOMELOTINIB	ChEMBL	Phase 4 (approved)	JAK1, JAK3
NINTEDANIB	ChEMBL	Phase 4 (approved)	JAK1, JAK3
PACRITINIB	ChEMBL	Phase 4 (approved)	JAK1, JAK3
PEFICITINIB	ChEMBL	Phase 4 (approved)	JAK1, JAK3
RUXOLITINIB	ChEMBL	Phase 4 (approved)	JAK1, JAK3
SUNITINIB	ChEMBL	Phase 4 (approved)	JAK1, JAK3
TOFACITINIB	ChEMBL	Phase 4 (approved)	JAK1, JAK3
UPADACITINIB	ChEMBL	Phase 4 (approved)	JAK1, JAK3
ABIVERTINIB	ChEMBL	Phase 3	JAK1, JAK3
BREPOCITINIB	ChEMBL	Phase 3	JAK1, JAK3
DELGOCITINIB	ChEMBL	Phase 3	JAK1, JAK3
DOVITINIB	ChEMBL	Phase 3	JAK1, JAK3
ITACITINIB	ChEMBL	Phase 3	JAK1, JAK3
LESTAURTINIB	ChEMBL	Phase 3	JAK1, JAK3
AT-9283	ChEMBL	Phase 2	JAK1, JAK3
ATINVICITINIB	ChEMBL	Phase 2	JAK1, JAK3
AZD-1480	ChEMBL	Phase 2	JAK1, JAK3
BMS-911543	ChEMBL	Phase 2	JAK1, JAK3
CC-401	ChEMBL	Phase 2	JAK1, JAK3
CERDULATINIB	ChEMBL	Phase 2	JAK1, JAK3
DECERNOTINIB	ChEMBL	Phase 2	JAK1, JAK3
GANDOTINIB	ChEMBL	Phase 2	JAK1, JAK3
GOLIDOCITINIB	ChEMBL	Phase 2	JAK1, JAK3
GUSACITINIB	ChEMBL	Phase 2	JAK1, JAK3
IFIDANCITINIB	ChEMBL	Phase 2	JAK1, JAK3
IZENCITINIB	ChEMBL	Phase 2	JAK1, JAK3
LEPZACITINIB	ChEMBL	Phase 2	JAK1, JAK3
NEZULCITINIB	ChEMBL	Phase 2	JAK1, JAK3
NS-018	ChEMBL	Phase 2	JAK1, JAK3
OCLACITINIB	ChEMBL	Phase 2	JAK1, JAK3
R-406	ChEMBL	Phase 2	JAK1, JAK3
ROPSACITINIB	ChEMBL	Phase 2	JAK1, JAK3
SOLCITINIB	ChEMBL	Phase 2	JAK1, JAK3
SOTRASTAURIN	ChEMBL	Phase 2	JAK1, JAK3
SU-014813	ChEMBL	Phase 2	JAK1, JAK3
TOZASERTIB	ChEMBL	Phase 2	JAK1, JAK3
Afatinib	PubChem	Approved	JAK1, JAK3
Gefitinib	PubChem	Approved	JAK1, JAK3
Idelalisib	PubChem	Approved	JAK1, JAK3
Selumetinib	PubChem	Approved	JAK1, JAK3
ACALABRUTINIB	ChEMBL	Phase 4 (approved)	JAK3
AXITINIB	ChEMBL	Phase 4 (approved)	JAK3
BOSUTINIB	ChEMBL	Phase 4 (approved)	JAK3
DASATINIB	ChEMBL	Phase 4 (approved)	JAK3
ERLOTINIB	ChEMBL	Phase 4 (approved)	JAK3
IBRUTINIB	ChEMBL	Phase 4 (approved)	JAK3
NERATINIB	ChEMBL	Phase 4 (approved)	JAK3
OSIMERTINIB	ChEMBL	Phase 4 (approved)	JAK3
PALBOCICLIB	ChEMBL	Phase 4 (approved)	JAK3