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Compound Detail

CHEMBL3813873

PEXIDARTINIB
💊 Approved Drug
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💊 Approved Drug
FC(F)(F)c1ccc(CNc2ccc(Cc3c[nH]c4ncc(Cl)cc34)cn2)cn1

Basic Information

ChEMBL ID CHEMBL3813873
Name PEXIDARTINIB
Phase Approved
Structure Type MOL
InChI Key JGWRKYUXBBNENE-UHFFFAOYSA-N
Therapeutic ✓ Yes

Known Names

CML-261 Pexidartinib Plx-3397 PLX3397
22
Targets
115
Activities
3
Assay Types
11
PK Parameters
20
Publications
4
Known Names
16
Indications
3
Mechanisms

Molecular Properties

417.8
MW (Da)
5.23
ALogP
4
HBA
2
HBD
66.5
PSA (Ų)
0.47
QED
1
Ro5 Violations
5
Rot. Bonds

Drug Information

Molecule Type Small molecule
First Approval 2019
Availability Prescription
Chirality Achiral

Routes of Administration

Oral

Flags

Black Box Warning First in Class Chemical Probe
USAN Stem -tinib
USAN Year 2017

Extended Properties

Molecular Formula C20H15ClF3N5
MW 417.82
Aromatic Rings 4
Heavy Atoms 29
NP-Likeness -1.35

Mechanism of Action

Mechanism Action Type Target Direct Efficacy
Macrophage colony stimulating factor receptor inhibitor INHIBITOR Macrophage colony-stimulating factor 1 receptor
Tyrosine-protein kinase receptor FLT3 inhibitor INHIBITOR Receptor-type tyrosine-protein kinase FLT3
Stem cell growth factor receptor inhibitor INHIBITOR Mast/stem cell growth factor receptor Kit

Indications

Neoplasms Synovitis, Pigmented Villonodular Breast Neoplasms Breast Neoplasms Glioblastoma Hemangiosarcoma Hodgkin Disease Melanoma Melanoma Prostatic Neoplasms, Castration-Resistant Arthritis, Rheumatoid Gastrointestinal Stromal Tumors Leukemia, Myeloid, Acute Neurilemmoma Prostatic Neoplasms Liver Diseases

ATC Classification

L01EX15
pexidartinib
Level 1: ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS
Level 2: ANTINEOPLASTIC AGENTS

Activity Summary

IC50 105 meas. best 9.96
Kd 8 meas. best 8.24
EC50 2 meas. best 6.7

Target Activity Profile

Target Type Best pChEMBL Mean pChEMBL Best (nM) # Data
BaF3
CHEMBL614524
IC50 9.96 7.4217 0.1 12
Unchecked
CHEMBL612545
IC50 8.8 7.71 1.6 4
Macrophage colony-stimulating factor 1 receptor
CHEMBL1844
IC50 8.77 7.88 1.7 34
Receptor-type tyrosine-protein kinase FLT3
CHEMBL1974
IC50 8.3 7.6013 5.0 16
Macrophage colony-stimulating factor 1 receptor
CHEMBL1844
Kd 8.24 7.34 5.8 4
Protein kinase C theta type
CHEMBL3920
Kd 8.22 8.22 6.0 1
Mast/stem cell growth factor receptor Kit
CHEMBL1936
IC50 8.16 7.6158 6.9 12
Platelet-derived growth factor receptor alpha
CHEMBL2007
IC50 8.02 7.5 9.6 4
Macrophage colony-stimulating factor 1 receptor
CHEMBL5570
IC50 7.85 7.425 14.0 2
NT-3 growth factor receptor
CHEMBL5608
IC50 7.7 6.875 20.0 2
NFS-60
CHEMBL614199
IC50 7.48 7.48 33.0 2
Platelet-derived growth factor receptor beta
CHEMBL1913
IC50 7.44 7.11 36.0 3
Receptor-type tyrosine-protein kinase FLT3
CHEMBL1974
Kd 7.26 7.26 55.0 1
BMDM
CHEMBL4296525
IC50 7.25 7.25 56.0 1
MV4-11
CHEMBL613835
IC50 6.7 6.7 200.0 1
BaF3
CHEMBL614524
EC50 6.7 6.7 200.0 1
NFS-60
CHEMBL614199
EC50 6.53 6.53 294.0 1
MOLM-14
CHEMBL3706570
IC50 6.46 6.2667 350.0 3
Vascular endothelial growth factor receptor 2
CHEMBL279
IC50 6.46 6.0333 350.0 3
RAW264.7
CHEMBL612557
IC50 6.4 6.385 400.0 2
Aurora kinase B
CHEMBL2185
IC50 6.19 6.19 643.0 1
Tyrosine-protein kinase Lck
CHEMBL258
IC50 6.07 6.07 860.0 1
Vascular endothelial growth factor receptor 1
CHEMBL1868
IC50 6.06 6.06 880.0 1
Uncharacterized protein FLJ45252
CHEMBL4105933
Kd 5.84 5.84 1452.0 1
SARS-CoV-2
CHEMBL4303835
IC50 5.26 5.26 5430.0 1
AP2-associated protein kinase 1
CHEMBL3830
Kd 4.86 4.86 13711.0 1

Pharmacokinetic Data

Parameter Value Units Species
AUC 18891.0 ng.hr.mL-1 Mus musculus
CL 0.8333 mL.min-1.kg-1 Mus musculus
CL 11.8 mL.min-1.g-1 Homo sapiens
CL 41.4 mL.min-1.g-1 Mus musculus
CL 61.2 mL.min-1.g-1 Rattus norvegicus
CL 0.8333 mL.min-1.kg-1 Mus musculus
CL 41.0 mL.min-1.g-1 Mus musculus
CL 12.0 mL.min-1.g-1 Homo sapiens
Fu 0.99 - Mus musculus
T1/2 5.6 hr Mus musculus
T1/2 5.6 hr Mus musculus

Activity Data Samples

Top measurements by pChEMBL value

Target Type Rel. Value Units pChEMBL Assay PubMed
BaF3 IC50 = 0.11 nM 9.96 Antiproliferative activity against mouse BaF3 harbouring CSF1R incubated for 72 ... 37191268
BaF3 IC50 = 0.17 nM 9.77 Antiproliferative activity against mouse BaF3 cells expressing FLT3-D835H 33719439
BaF3 IC50 = 0.19 nM 9.72 Antiproliferative activity against mouse BaF3 cells expressing FLT3-D835Y 33719439
Unchecked IC50 = 1.6 nM 8.8 Inhibition of His-Glu tagged recombinant human KIT Q694-T753 deletion mutant (56... 35961460
Macrophage colony-stimulating factor 1 receptor IC50 = 1.7 nM 8.77 Inhibition of N-terminal His6-tagged recombinant human CSF1R (542 to 919 residue... 35961460
Macrophage colony-stimulating factor 1 receptor IC50 = 1.7 nM 8.77 Inhibition of N-terminal His6-tagged recombinant human CSF1R (542 to 919 residue... 35961461
Macrophage colony-stimulating factor 1 receptor IC50 = 2.2 nM 8.66 CSF1R Kinase Assay: The activity of CSF1R kinase (CSF1R, SEQ ID NO: 1) was deter... -
BaF3 IC50 = 2.5 nM 8.6 Antiproliferative activity against mouse BaF3 cells expressing FLT3-D835V 33719439
Macrophage colony-stimulating factor 1 receptor IC50 = 4.7 nM 8.33 Inhibition of CSF1R (unknown origin) using EEEIYGEFE as substrate in presence of... 38141285
Receptor-type tyrosine-protein kinase FLT3 IC50 = 5.0 nM 8.3 Competitive inhibition of FLT3 D835Y mutant (unknown origin) in presence of ATP 27190596
Macrophage colony-stimulating factor 1 receptor IC50 = 5.0 nM 8.3 Inhibition of CSF1R (unknown origin) in presence of ATP by Z-LYTE based FRET ass... 37191268
Macrophage colony-stimulating factor 1 receptor IC50 = 5.61 nM 8.25 Inhibition of CSF1R (unknown origin) using poly (4:1 Glu, Tyr) peptide as substr... 36179404
Macrophage colony-stimulating factor 1 receptor Kd = 5.8 nM 8.24 Binding affinity to non-autoinhibited CSF1R (564 to 939) (unknown origin) expres... 37191268
Macrophage colony-stimulating factor 1 receptor Kd = 5.8 nM 8.24 Binding affinity to non-autoinhibited form of CSF1R (unknown origin) assessed as... 37141705
Protein kinase C theta type Kd = 6.0 nM 8.22 Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase ... 29191878
Mast/stem cell growth factor receptor Kit IC50 = 6.9 nM 8.16 c-Kit Kinase Assay: The activity of unphosphorylated c-KIT kinase (c-KIT, SEQ ID... -
Receptor-type tyrosine-protein kinase FLT3 IC50 = 7.1 nM 8.15 FLT3 Kinase Assay: The activity of FLT3 kinase was determined spectroscopically ... -
Receptor-type tyrosine-protein kinase FLT3 IC50 = 7.1 nM 8.15 Inhibition of His-tagged recombinant human FLT3 (564 to 958 residues) measured b... 35961461
Receptor-type tyrosine-protein kinase FLT3 IC50 = 7.1 nM 8.15 Inhibition of His-tagged recombinant human FLT3 (564 to 958 residues) measured b... 35961460
Receptor-type tyrosine-protein kinase FLT3 IC50 = 9.0 nM 8.05 Inhibition of FLT3 (unknown origin) 36335744

Literature References

PubMed DOI Target Context # Activities
37191268 10.1021/acs.jmedchem.3c00428 ADMET 12
- 10.6019/CHEMBL5303304 Fibroblast 10
34735158 10.1021/acs.jmedchem.1c01184 MC-38 9
31434879 10.1038/s41467-019-11674-z ADMET 9
31434879 10.1038/s41467-019-11674-z Mus musculus 9
31434879 10.1038/s41467-019-11674-z Macrophage colony-stimulating factor 1 receptor 8
37141705 10.1016/j.ejmech.2023.115344 ADMET 8
37191268 10.1021/acs.jmedchem.3c00428 Macrophage colony-stimulating factor 1 receptor 7
38141285 10.1016/j.ejmech.2023.116053 ADMET 6
33719439 10.1021/acs.jmedchem.0c01851 BaF3 6
38593344 10.1021/acs.jmedchem.4c00508 MC-38 6
29191878 10.1126/science.aan4368 Unchecked 4
31434879 10.1038/s41467-019-11674-z Unchecked 4
- 10.6019/CHEMBL4495565 SARS-CoV-2 4
34735158 10.1021/acs.jmedchem.1c01184 HCT-116 4
37141705 10.1016/j.ejmech.2023.115344 Macrophage colony-stimulating factor 1 receptor 4
36179404 10.1016/j.ejmech.2022.114782 BaF3 4
33689933 10.1016/j.ejmech.2021.113298 Macrophage colony-stimulating factor 1 receptor 4
38141285 10.1016/j.ejmech.2023.116053 Macrophage colony-stimulating factor 1 receptor 3
36179404 10.1016/j.ejmech.2022.114782 NFS-60 3

Data from ChEMBL 36 via Core Engine