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Compound Detail

CHEMBL4085457

RITLECITINIB
💊 Approved Drug
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💊 Approved Drug
C=CC(=O)N1C[C@H](Nc2ncnc3[nH]ccc23)CC[C@@H]1C

Basic Information

ChEMBL ID CHEMBL4085457
Name RITLECITINIB
Phase Approved
Structure Type MOL
InChI Key CBRJPFGIXUFMTM-WDEREUQCSA-N
Therapeutic ✓ Yes

Known Names

Pf-06651600 Ritlecitinib
12
Targets
44
Activities
2
Assay Types
23
PK Parameters
20
Publications
2
Known Names
13
Indications
2
Mechanisms

Molecular Properties

285.4
MW (Da)
1.94
ALogP
4
HBA
2
HBD
73.9
PSA (Ų)
0.85
QED
0
Ro5 Violations
3
Rot. Bonds

Drug Information

Molecule Type Small molecule
First Approval 2023
Availability Prescription
Chirality Single Enantiomer

Routes of Administration

Oral

Flags

Black Box Warning
USAN Stem -tinib

Extended Properties

Molecular Formula C15H19N5O
MW 285.35
Aromatic Rings 2
Heavy Atoms 21
NP-Likeness -0.84

Mechanism of Action

Mechanism Action Type Target Direct Efficacy
Tyrosine-protein kinase JAK3 inhibitor INHIBITOR Tyrosine-protein kinase JAK3
TEC family kinase inhibitor INHIBITOR TEC family kinase

Indications

Alopecia Areata Vitiligo Alopecia Arthritis, Rheumatoid Celiac Disease Colitis, Ulcerative Crohn Disease Diabetes Mellitus, Type 1 Keloid Mycosis Fungoides Sezary Syndrome Kidney Diseases Liver Diseases

ATC Classification

L04AF08
ritlecitinib
Level 1: ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS
Level 2: IMMUNOSUPPRESSANTS

Activity Summary

IC50 37 meas. best 9.52
Ki 7 meas. best 7.57

Target Activity Profile

Target Type Best pChEMBL Mean pChEMBL Best (nM) # Data
Tyrosine-protein kinase JAK3
CHEMBL2148
IC50 9.52 8.027 0.3 23
U-937
CHEMBL612794
IC50 7.71 7.555 19.5 2
Tyrosine-protein kinase ITK/TSK
CHEMBL2959
Ki 7.57 7.57 26.9 1
BaF3
CHEMBL614524
IC50 7.55 7.55 28.1 1
CD4+ve Th
CHEMBL613544
IC50 7.32 7.32 48.0 1
Tyrosine-protein kinase TXK
CHEMBL4367
Ki 6.88 6.88 131.0 1
Tyrosine-protein kinase Tec
CHEMBL4246
IC50 6.81 6.52 155.0 2
Tyrosine-protein kinase TXK
CHEMBL4367
IC50 6.71 6.71 193.0 1
Cytoplasmic tyrosine-protein kinase BMX
CHEMBL3834
Ki 6.26 6.26 545.0 1
Cytoplasmic tyrosine-protein kinase BMX
CHEMBL3834
IC50 6.22 6.22 606.0 1
Tyrosine-protein kinase BTK
CHEMBL5251
IC50 6.22 6.22 607.0 1
Tyrosine-protein kinase Tec
CHEMBL4246
Ki 6.17 6.17 679.0 1
Tyrosine-protein kinase JAK1
CHEMBL2835
IC50 5.79 5.79 1640.0 2
Tyrosine-protein kinase JAK3
CHEMBL2148
Ki 5.2 5.2 6310.0 1
Tyrosine-protein kinase ITK/TSK
CHEMBL2959
IC50 5.07 5.07 8510.0 1
Tyrosine-protein kinase Blk
CHEMBL2250
IC50 4.72 4.72 19000.0 1
Receptor tyrosine-protein kinase erbB-4
CHEMBL3009
IC50 4.6 4.6 25200.0 1
Tyrosine-protein kinase Blk
CHEMBL2250
Ki 4.49 4.49 32400.0 1
Tyrosine-protein kinase BTK
CHEMBL5251
Ki 4.21 4.21 62300.0 1

Pharmacokinetic Data

Parameter Value Units Species
CL 48.0 mL.min-1.kg-1 Mus musculus
CL 53.0 mL.min-1.kg-1 Rattus norvegicus
CL 42.0 mL.min-1.kg-1 Macaca mulatta
CL 8.6 mL.min-1.kg-1 Canis lupus familiaris
F 62.0 % Mus musculus
F 85.0 % Rattus norvegicus
F 56.0 % Macaca mulatta
F 109.0 % Canis lupus familiaris
T1/2 6.0 hr Homo sapiens
T1/2 2.683 hr Rattus norvegicus
T1/2 6.0 hr Mus musculus
T1/2 2.683 hr Rattus norvegicus
T1/2 0.6167 hr Macaca mulatta
T1/2 6.0 hr Canis lupus familiaris
T1/2 6.0 hr Homo sapiens
T1/2 5.517 hr Homo sapiens
T1/2 1.3 hr Mus musculus
T1/2 0.3 hr Rattus norvegicus
T1/2 0.7 hr Macaca mulatta
T1/2 1.1 hr Canis lupus familiaris
T1/2 8.0 hr Homo sapiens
t1/2 - - -
T1/2 32.0 hr -

Activity Data Samples

Top measurements by pChEMBL value

Target Type Rel. Value Units pChEMBL Assay PubMed
Tyrosine-protein kinase JAK3 IC50 = 0.3 nM 9.52 Inhibition of recombinant human GST-tagged JAK3 JH1 domain using KAIETDKEYYTVKD-... 30423248
Tyrosine-protein kinase JAK3 IC50 = 0.3 nM 9.52 Inhibition of human recombinant GST tagged JAK3 kinase domain (781 to 1124 amino... 31266686
Tyrosine-protein kinase JAK3 IC50 = 0.3 nM 9.52 JAK Caliper Enzyme Assay: Test article was solubilized in dimethyl sulfoxide (DM... -
Tyrosine-protein kinase JAK3 IC50 = 0.3 nM 9.52 Caliper Enzyme Assay (4 uM ATP): JAK Caliper Enzyme Assay at 4 μM: Test article ... -
Tyrosine-protein kinase JAK3 IC50 = 0.3 nM 9.52 Inhibition of recombinant human GST-tagged cytoplasmic JAK3 catalytic domain (78... 28139931
Tyrosine-protein kinase JAK3 IC50 = 0.35 nM 9.46 Inhibition of JAK3 (unknown origin) 28844493
Tyrosine-protein kinase JAK3 IC50 = 0.4 nM 9.4 Inhibition of human N-terminal His-tagged JAK3 (795 to 1124 residues) expressed ... 30615446
Tyrosine-protein kinase JAK3 IC50 = 2.3 nM 8.64 Inhibition of GST tagged recombinant human JAK3 expressed in baculovirus infecti... 35860875
U-937 IC50 = 19.5 nM 7.71 Antiproliferative activity against human U-937 cells harboring JAK3 M511135 muta... 35860875
Tyrosine-protein kinase ITK/TSK Ki = 26.9 nM 7.57 Inhibition of full length recombinant human GST-tagged cytoplasmic ITK expressed... 28139931
BaF3 IC50 = 28.1 nM 7.55 Antiproliferative activity against mouse BaF3 cells harboring JAK3 M5111 mutant ... 35860875
Tyrosine-protein kinase JAK3 IC50 = 33.1 nM 7.48 Inhibition of JAK3 (unknown origin) 30853331
Tyrosine-protein kinase JAK3 IC50 = 33.1 nM 7.48 Inhibition of JAK 3 (unknown origin) 33539089
Tyrosine-protein kinase JAK3 IC50 = 33.0 nM 7.48 Inhibition of recombinant human GST-tagged cytoplasmic JAK3 catalytic domain (78... 28139931
Tyrosine-protein kinase JAK3 IC50 = 33.0 nM 7.48 Inhibition of JAK3 (unknown origin) 31318208
Tyrosine-protein kinase JAK3 IC50 = 33.0 nM 7.48 Inhibition of JAK3 (unknown origin) in presence of ATP 35749986
Tyrosine-protein kinase JAK3 IC50 = 33.1 nM 7.48 Inhibition of human recombinant His-tagged JAK3 expressed in baculovirus-infecte... 37793326
Tyrosine-protein kinase JAK3 IC50 = 33.1 nM 7.48 JAK Caliper Enzyme Assay: Test article was solubilized in dimethyl sulfoxide (DM... -
Tyrosine-protein kinase JAK3 IC50 = 33.1 nM 7.48 Caliper Enzyme Assay (4 mM ATP): JAK Caliper Enzyme Assay at 1 mM ATP: Test arti... -
Tyrosine-protein kinase JAK3 IC50 = 33.0 nM 7.48 Inhibition of recombinant human GST-tagged JAK3 JH1 domain using KAIETDKEYYTVKD-... 30423248

Literature References

PubMed DOI Target Context # Activities
28139931 10.1021/acs.jmedchem.6b01694 Tyrosine-protein kinase JAK3 10
30615446 10.1021/acs.jmedchem.8b01823 Tyrosine-protein kinase JAK3 6
28139931 10.1021/acs.jmedchem.6b01694 Blood 6
35436668 10.1016/j.ejmech.2022.114374 No relevant target 5
28139931 10.1021/acs.jmedchem.6b01694 Tyrosine-protein kinase TXK 4
28139931 10.1021/acs.jmedchem.6b01694 Tyrosine-protein kinase ITK/TSK 4
28139931 10.1021/acs.jmedchem.6b01694 Cytoplasmic tyrosine-protein kinase BMX 4
28139931 10.1021/acs.jmedchem.6b01694 Canis familiaris 4
28139931 10.1021/acs.jmedchem.6b01694 Rhesus monkey 4
28139931 10.1021/acs.jmedchem.6b01694 Rattus norvegicus 4
28139931 10.1021/acs.jmedchem.6b01694 Mus musculus 4
28139931 10.1021/acs.jmedchem.6b01694 Tyrosine-protein kinase Tec 4
28139931 10.1021/acs.jmedchem.6b01694 ADMET 4
28139931 10.1021/acs.jmedchem.6b01694 Tyrosine-protein kinase BTK 4
35860875 10.1021/acs.jmedchem.2c00922 BaF3 4
28139931 10.1021/acs.jmedchem.6b01694 Tyrosine-protein kinase Blk 4
30423248 10.1021/acs.jmedchem.8b01308 Tyrosine-protein kinase JAK3 3
28139931 10.1021/acs.jmedchem.6b01694 Unchecked 3
35436668 10.1016/j.ejmech.2022.114374 ADMET 3
37793326 10.1016/j.ejmech.2023.115848 Tyrosine-protein kinase JAK3 2

Data from ChEMBL 36 via Core Engine