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Compound Detail

CHEMBL4297522

PEMIGATINIB
💊 Approved Drug
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💊 Approved Drug
CCN1C(=O)N(c2c(F)c(OC)cc(OC)c2F)Cc2cnc3[nH]c(CN4CCOCC4)cc3c21

Basic Information

ChEMBL ID CHEMBL4297522
Name PEMIGATINIB
Phase Approved
Structure Type MOL
InChI Key HCDMJFOHIXMBOV-UHFFFAOYSA-N
Therapeutic ✓ Yes

Known Names

Fgfr inhibitor incb054828 Incb-054828 Incb054828 Pemazyre Pemigatinib
12
Targets
48
Activities
1
Assay Types
13
PK Parameters
20
Publications
5
Known Names
14
Indications
3
Mechanisms

Molecular Properties

487.5
MW (Da)
3.66
ALogP
6
HBA
1
HBD
83.2
PSA (Ų)
0.57
QED
0
Ro5 Violations
6
Rot. Bonds

Drug Information

Molecule Type Small molecule
First Approval 2020
Availability Prescription
Chirality Achiral

Routes of Administration

Oral
USAN Stem -tinib
USAN Year 2018

Extended Properties

Molecular Formula C24H27F2N5O4
MW 487.51
Aromatic Rings 3
Heavy Atoms 35
NP-Likeness -0.90

Mechanism of Action

Mechanism Action Type Target Direct Efficacy
Fibroblast growth factor receptor 2 inhibitor INHIBITOR Fibroblast growth factor receptor 2
Fibroblast growth factor receptor 3 inhibitor INHIBITOR Fibroblast growth factor receptor 3
Fibroblast growth factor receptor 1 inhibitor INHIBITOR Fibroblast growth factor receptor 1

Indications

Cholangiocarcinoma Neoplasms Neoplasms Breast Neoplasms Carcinoma, Non-Small-Cell Lung Colorectal Neoplasms Endometrial Neoplasms Liposarcoma Myeloproliferative Disorders Pancreatic Neoplasms Stomach Neoplasms Urinary Bladder Neoplasms Urogenital Neoplasms Leukemia, Myeloid, Acute

ATC Classification

L01EN02
pemigatinib
Level 1: ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS
Level 2: ANTINEOPLASTIC AGENTS

Activity Summary

IC50 48 meas. best 10.0

Target Activity Profile

Target Type Best pChEMBL Mean pChEMBL Best (nM) # Data
Fibroblast growth factor receptor 3
CHEMBL2742
IC50 10.0 8.202 0.1 10
Fibroblast growth factor receptor 1
CHEMBL3650
IC50 9.4 8.7214 0.4 7
Fibroblast growth factor receptor 2
CHEMBL4142
IC50 9.4 8.7 0.4 7
Unchecked
CHEMBL612545
IC50 8.59 7.6433 2.6 3
KATO III stomach cancer cell line
CHEMBL612700
IC50 8.51 8.51 3.1 1
RT-112
CHEMBL614145
IC50 8.48 7.362 3.3 5
CC-LP-1
CHEMBL6066762
IC50 8.44 6.9625 3.6 4
SNU-16
CHEMBL613529
IC50 8.41 8.32 3.9 2
A204
CHEMBL614514
IC50 7.74 7.74 18.4 1
Fibroblast growth factor receptor 2
CHEMBL3648
IC50 7.66 7.66 22.0 1
Fibroblast growth factor receptor 4
CHEMBL3973
IC50 7.57 7.455 27.0 6
MDA-MB-453
CHEMBL614334
IC50 7.13 7.13 73.7 1

Pharmacokinetic Data

Parameter Value Units Species
AUC 3739.2 ng.hr.mL-1 Rattus norvegicus
AUC 3017.69 ng.hr.mL-1 Macaca fascicularis
AUC 10773.97 ng.hr.mL-1 Canis lupus familiaris
CL 8.0 % Macaca fascicularis
CL 31.0 % Rattus norvegicus
CL 10.0 % Canis lupus familiaris
F 100.0 % Rattus norvegicus
F 29.0 % Macaca fascicularis
F 98.0 % Canis lupus familiaris
Fu 0.11 - Homo sapiens
T1/2 4.0 hr Rattus norvegicus
T1/2 10.0 hr Macaca fascicularis
T1/2 15.7 hr Canis lupus familiaris

Activity Data Samples

Top measurements by pChEMBL value

Target Type Rel. Value Units pChEMBL Assay PubMed
Fibroblast growth factor receptor 3 IC50 = 0.1 nM 10.0 Inhibition of human recombinant FGFR3 by enzymatic assay 37657268
Fibroblast growth factor receptor 1 IC50 = 0.4 nM 9.4 Inhibition of human recombinant FGFR1 by enzymatic assay 37657268
Fibroblast growth factor receptor 1 IC50 = 0.4 nM 9.4 Inhibition of FGFR1 (unknown origin) 38908103
Fibroblast growth factor receptor 2 IC50 = 0.4 nM 9.4 Inhibition of N-terminal GST tagged recombinant human FGFR2 (400 to 821 residues... 36356320
Fibroblast growth factor receptor 1 IC50 = 0.4 nM 9.4 Inhibition of FGFR1 (unknown origin) 33199155
Fibroblast growth factor receptor 1 IC50 = 0.4 nM 9.4 Inhibition of FGFR1 (unknown origin) 33940465
Fibroblast growth factor receptor 2 IC50 = 0.5 nM 9.3 Inhibition of FGFR2 (unknown origin) 33940465
Fibroblast growth factor receptor 2 IC50 = 0.5 nM 9.3 Inhibition of FGFR2 (unknown origin) 33199155
Fibroblast growth factor receptor 2 IC50 = 0.5 nM 9.3 Inhibition of FGFR2 (unknown origin) 38908103
Fibroblast growth factor receptor 2 IC50 = 0.5 nM 9.3 Inhibition of human recombinant FGFR2 by enzymatic assay 37657268
Fibroblast growth factor receptor 1 IC50 = 0.9 nM 9.05 Inhibition of recombinant human FGFR1 using biotin-EQEDEPEGDYFEWLE-amide as subs... 36356320
Fibroblast growth factor receptor 3 IC50 = 0.97 nM 9.01 Inhibition of wild-type FGFR3 (unknown origin) by radiometric kinase activity as... 35436119
Fibroblast growth factor receptor 3 IC50 = 1.0 nM 9.0 Inhibition of FGFR3 (unknown origin) 33199155
Fibroblast growth factor receptor 3 IC50 = 1.2 nM 8.92 Inhibition of FGFR3 (unknown origin) 38908103
Fibroblast growth factor receptor 3 IC50 = 1.2 nM 8.92 Inhibition of FGFR3 (unknown origin) 33940465
Fibroblast growth factor receptor 3 IC50 = 1.7 nM 8.77 Inhibition of N-terminal His-Avi tagged recombinant human FGFR3 (447 to 761 resi... 36356320
Fibroblast growth factor receptor 1 IC50 = 1.88 nM 8.73 Inhibition of wild-type FGFR1 (unknown origin) by radiometric kinase activity as... 35436119
Unchecked IC50 = 2.6 nM 8.59 Antiproliferative activity against human ICC13-7 cells assessed as inhibition of... 38267212
KATO III stomach cancer cell line IC50 = 3.1 nM 8.51 Antiproliferation activity against human KATO III cells harboring FGFR2 amplific... 38718625
RT-112 IC50 = 3.3 nM 8.48 Antiproliferative activity against human RT-112 cells assessed as inhibition of ... 38267212

Literature References

PubMed DOI Target Context # Activities
- 10.6019/CHEMBL5303300 Fibroblast 304
- 10.6019/CHEMBL5303300 U2OS 304
- 10.6019/CHEMBL5303300 HEK-293T 304
34269576 10.1021/acs.jmedchem.1c00713 ADMET 18
34269576 10.1021/acs.jmedchem.1c00713 Unchecked 13
- 10.6019/CHEMBL5303304 U2OS 10
- 10.6019/CHEMBL5303304 Fibroblast 9
- 10.6019/CHEMBL5303304 HEK-293T 8
35436119 10.1021/acs.jmedchem.1c01776 BaF3 5
38267212 10.1021/acs.jmedchem.3c01819 RT-112 5
38267212 10.1021/acs.jmedchem.3c01819 CC-LP-1 4
35436119 10.1021/acs.jmedchem.1c01776 Fibroblast growth factor receptor 3 4
38267212 10.1021/acs.jmedchem.3c01819 Unchecked 4
35436119 10.1021/acs.jmedchem.1c01776 Fibroblast growth factor receptor 2 3
36356320 10.1021/acs.jmedchem.2c01366 Fibroblast growth factor receptor 3 3
34269576 10.1021/acs.jmedchem.1c00713 Glutamate [NMDA] receptor 3
35436119 10.1021/acs.jmedchem.1c01776 Fibroblast growth factor receptor 1 2
34269576 10.1021/acs.jmedchem.1c00713 Voltage-gated inwardly rectifying potassium channel KCNH2 2
34269576 10.1021/acs.jmedchem.1c00713 No relevant target 2
34269576 10.1021/acs.jmedchem.1c00713 Fibroblast growth factor receptor 2 1

Data from ChEMBL 36 via Core Engine