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Compound Detail

CHEMBL3545154

POZIOTINIB
🧪 Phase III
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🧪 Phase III
C=CC(=O)N1CCC(Oc2cc3c(Nc4ccc(Cl)c(Cl)c4F)ncnc3cc2OC)CC1

Basic Information

ChEMBL ID CHEMBL3545154
Name POZIOTINIB
Phase Phase III
Structure Type MOL
InChI Key LPFWVDIFUFFKJU-UHFFFAOYSA-N

Known Names

HM 781-36 HM 781-36B HM-781-36 Hm-781-36b HM781-36B NOV-1201 NOV-120101 Poziotinib
19
Targets
66
Activities
3
Assay Types
4
PK Parameters
20
Publications
8
Known Names
9
Indications
1
Mechanisms

Molecular Properties

491.4
MW (Da)
5.38
ALogP
6
HBA
1
HBD
76.6
PSA (Ų)
0.37
QED
1
Ro5 Violations
6
Rot. Bonds

Drug Information

Molecule Type Small molecule
Chirality Achiral
USAN Stem -tinib
USAN Year 2020

Extended Properties

Molecular Formula C23H21Cl2FN4O3
MW 491.35
Aromatic Rings 3
Heavy Atoms 33
NP-Likeness -0.82

Mechanism of Action

Mechanism Action Type Target Direct Efficacy
Epidermal growth factor receptor inhibitor INHIBITOR Epidermal growth factor receptor

Indications

Carcinoma, Non-Small-Cell Lung Adenocarcinoma of Lung Breast Neoplasms Esophageal Neoplasms Head and Neck Neoplasms Lung Neoplasms Neoplasms Neoplasms Stomach Neoplasms

Activity Summary

IC50 52 meas. best 10.21
Kd 11 meas. best 8.7
EC50 3 meas. best 8.15

Target Activity Profile

Target Type Best pChEMBL Mean pChEMBL Best (nM) # Data
Epidermal growth factor receptor
CHEMBL203
IC50 10.21 8.9861 0.1 23
Unchecked
CHEMBL612545
IC50 10.09 8.5669 0.1 16
BaF3
CHEMBL614524
IC50 9.68 9.3 0.2 5
A-431
CHEMBL614069
IC50 9.05 9.05 0.9 1
SK-BR-3
CHEMBL613834
IC50 9.0 9.0 1.0 1
Receptor tyrosine-protein kinase erbB-2
CHEMBL1824
IC50 8.88 8.36 1.3 3
Epidermal growth factor receptor
CHEMBL203
Kd 8.7 8.7 2.0 1
NON-PROTEIN TARGET
CHEMBL3879801
IC50 8.57 8.57 2.7 1
Tyrosine-protein kinase BTK
CHEMBL5251
Kd 8.52 8.52 3.0 1
NCI-H1975
CHEMBL614348
IC50 8.24 8.24 5.7 1
Unchecked
CHEMBL612545
EC50 8.15 8.15 7.0 1
BaF3
CHEMBL614524
EC50 7.92 7.92 12.0 1
Receptor-interacting serine/threonine-protein kinase 2
CHEMBL5014
Kd 7.32 7.32 48.0 1
Tyrosine-protein kinase Tec
CHEMBL4246
Kd 7.16 7.16 69.0 1
Ephrin type-B receptor 4
CHEMBL5147
Kd 6.47 6.47 340.0 1
Receptor-interacting serine/threonine-protein kinase 3
CHEMBL1795199
Kd 6.41 6.41 392.0 1
Hepatocyte growth factor receptor
CHEMBL3717
Kd 6.1 6.1 794.0 1
Voltage-gated inwardly rectifying potassium channel KCNH2
CHEMBL240
IC50 6.04 6.04 915.0 1
Proto-oncogene tyrosine-protein kinase receptor Ret
CHEMBL2041
Kd 5.93 5.93 1185.0 1
A-431
CHEMBL614069
EC50 5.84 5.84 1445.0 1
Non-receptor tyrosine-protein kinase TNK1
CHEMBL5334
Kd 5.77 5.77 1682.0 1
Ephrin type-B receptor 2
CHEMBL3290
Kd 5.65 5.65 2236.0 1
Ephrin type-A receptor 4
CHEMBL3988
Kd 5.15 5.15 7057.0 1

Pharmacokinetic Data

Parameter Value Units Species
CL 35.4 mL.min-1.g-1 Mus musculus
CL 22.0 mL.min-1.g-1 Homo sapiens
CL 44.0 mL.min-1.g-1 Homo sapiens
T1/2 15.63 hr -

Activity Data Samples

Top measurements by pChEMBL value

Target Type Rel. Value Units pChEMBL Assay PubMed
Epidermal growth factor receptor IC50 = 0.061 nM 10.21 Inhibition of EGFR D770-N771 ins NPG mutant (unknown origin) 36804726
Epidermal growth factor receptor IC50 = 0.078 nM 10.11 Inhibition of GST-tagged human EGFR A763_Y764insFHEA mutant using poly(Glu, Tyr)... 31560541
Unchecked IC50 = 0.082 nM 10.09 Inhibition of GST-tagged human EGFR D770GY mutant using poly(Glu, Tyr) 4:1 subst... 31560541
Epidermal growth factor receptor IC50 = 0.137 nM 9.86 Inhibition of wild type EGFR (unknown origin) 36804726
Epidermal growth factor receptor IC50 = 0.151 nM 9.82 Inhibition of EGFR L858R mutant (unknown origin) 36804726
Unchecked IC50 = 0.206 nM 9.69 Inhibition of GST-tagged human HER2 V777_G778insCG mutant mutant using poly(Glu,... 31560541
BaF3 IC50 = 0.21 nM 9.68 Antiproliferative activity against mouse BAF3 cells harboring HER2-P780-Y781 ins... 36804726
Epidermal growth factor receptor IC50 = 0.218 nM 9.66 Inhibition of GST-tagged human EGFR D770_N771insNPG mutant using poly(Glu, Tyr) ... 31560541
Epidermal growth factor receptor IC50 = 0.2512 nM 9.6 Inhibition of wild type N-terminal GST-tagged EGFR (669 to 1210 residues) (unkno... 38746885
Epidermal growth factor receptor IC50 = 0.262 nM 9.58 Inhibition of EGFR A763-Y764 ins FQEA mutant (unknown origin) 36804726
Epidermal growth factor receptor IC50 = 0.27 nM 9.57 Inhibition of recombinant human N-terminal GST-tagged EGFR (669 to 1210 residues... 35364239
Unchecked IC50 = 0.3 nM 9.52 Antiproliferative activity against human YUL-0019 cells harboring EGFR N771delin... 37669428
Unchecked IC50 = 0.3 nM 9.52 Inhibition of C-terminal His6-tagged HER2-A775_G776insYVMA mutant (703 to 1029 r... 32931277
Epidermal growth factor receptor IC50 = 0.3981 nM 9.4 Inhibition of wild type N-terminal GST-tagged EGFR (669 to 1210 residues) (unkno... 38746885
Unchecked IC50 = 0.401 nM 9.4 Inhibition of EGFR L858R/T790M double mutant (unknown origin) 36804726
Epidermal growth factor receptor IC50 = 0.3981 nM 9.4 Inhibition of wild type N-terminal GST-tagged EGFR (669 to 1210 residues) (unkno... 38746885
BaF3 IC50 = 0.43 nM 9.37 Antiproliferative activity against mouse BAF3 cells harboring HER2-A775-G776 ins... 36804726
BaF3 IC50 = 0.58 nM 9.24 Antiproliferative activity against mouse BAF3 cells harboring FL-EGFR A763-Y764 ... 36804726
BaF3 IC50 = 0.62 nM 9.21 Antiproliferative activity against mouse BAF3 cells harboring FL-EGFR D770-N771 ... 36804726
Unchecked IC50 = 0.7 nM 9.15 Antiproliferative activity against mouse Ba/F3 EGFR-A763_Y764insFQEA cells incub... 37669428

Literature References

Data from ChEMBL 36 via Core Engine