Compound Detail

CHEMBL1171837

PONATINIB

💊 Approved Drug

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💊 Approved Drug

Cc1ccc(C(=O)Nc2ccc(CN3CCN(C)CC3)c(C(F)(F)F)c2)cc1C#Cc1cnc2cccnn12

ChEMBL ↗ Properties Compare Identifier

Basic Information

ChEMBL ID	CHEMBL1171837
Name	PONATINIB
Phase	Approved
Structure Type	MOL
InChI Key	PHXJVRSECIGDHY-UHFFFAOYSA-N
Therapeutic	✓ Yes

Known Names

AP-24534 AP24534 Iclusig Ponatinib

738

Targets

948

Activities

Assay Types

PK Parameters

Publications

Known Names

Indications

Molecular Properties

532.6

MW (Da)

4.46

ALogP

HBA

HBD

65.8

PSA (Å²)

0.39

QED

Ro5 Violations

Rot. Bonds

Drug Information

Molecule Type	Small molecule
First Approval	2012
Availability	Prescription
Chirality	Achiral

Routes of Administration

Oral

Flags

Black Box Warning

USAN Stem	-tinib
USAN Year	2010

Extended Properties

Molecular Formula	C29H27F3N6O
MW	532.57
Aromatic Rings	4
Heavy Atoms	39
NP-Likeness	-1.80

Indications

Leukemia, Myelogenous, Chronic, BCR-ABL Positive Neoplasms Precursor Cell Lymphoblastic Leukemia-Lymphoma Adenocarcinoma of Lung Blast Crisis Carcinoma, Medullary Carcinoma, Non-Small-Cell Lung Gastrointestinal Stromal Tumors Glioblastoma Leukemia Leukemia, Myeloid, Acute Small Cell Lung Carcinoma Thyroid Neoplasms Myelodysplastic Syndromes

ATC Classification

L01EA05

ponatinib

Level 1: ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS

Level 2: ANTINEOPLASTIC AGENTS

Activity Summary

IC50 873 meas. best 10.02

Kd 54 meas. best 8.15

EC50 20 meas. best 10.3

Ki 1 meas. best 8.82

Target Activity Profile

Target	Type	Best pChEMBL	Mean pChEMBL	Best (nM)	# Data
Bcr/Abl fusion protein CHEMBL2096618	EC50	10.3	8.8817	0.1	6
MV4-11 CHEMBL613835	IC50	10.02	10.02	0.1	1
KU812 cell line CHEMBL613997	IC50	10.0	8.5367	0.1	3
Tyrosine-protein kinase HCK CHEMBL3234	IC50	9.96	9.96	0.1	1
MEG-01 CHEMBL2366084	IC50	9.89	9.89	0.1	1
Tyrosine-protein kinase Lyn CHEMBL3905	IC50	9.8	9.38	0.2	3
LAMA-84 CHEMBL2366090	IC50	9.78	9.78	0.2	1
Tyrosine-protein kinase Lck CHEMBL258	IC50	9.55	9.55	0.3	1
Tyrosine-protein kinase ABL1 CHEMBL1862	IC50	9.52	8.9741	0.3	37
Receptor-type tyrosine-protein kinase FLT3 CHEMBL1974	IC50	9.52	8.145	0.3	6
Proto-oncogene tyrosine-protein kinase receptor Ret CHEMBL2041	IC50	9.52	8.0356	0.3	9
K562 CHEMBL385	IC50	9.52	8.1486	0.3	7
Tyrosine-protein kinase Fyn CHEMBL1841	IC50	9.44	9.44	0.4	1
K562 CHEMBL385	EC50	9.41	9.0975	0.4	4
Bcr/Abl fusion protein CHEMBL2096618	IC50	9.3	8.9043	0.5	7
Fibroblast growth factor receptor 1 CHEMBL3650	IC50	9.15	8.8813	0.7	8
Tyrosine-protein kinase Yes CHEMBL2073	IC50	9.05	9.05	0.9	1
Proto-oncogene tyrosine-protein kinase Src CHEMBL3655	IC50	9.05	9.05	0.9	1
BaF3 CHEMBL614524	IC50	9.05	7.506	0.9	10
Receptor-interacting serine/threonine-protein kinase 2 CHEMBL5014	IC50	9.0	8.44	1.0	3
Platelet-derived growth factor receptor alpha CHEMBL2007	IC50	8.96	8.8367	1.1	3
Unchecked CHEMBL612545	IC50	8.96	7.3177	1.1	13
Platelet-derived growth factor receptor beta CHEMBL1913	IC50	8.92	8.92	1.2	1
NON-PROTEIN TARGET CHEMBL3879801	IC50	8.92	7.7017	1.2	6
Fibroblast growth factor receptor 2 CHEMBL4142	IC50	8.89	8.795	1.3	2
Tyrosine-protein kinase FRK CHEMBL4223	IC50	8.89	8.89	1.3	1
Vascular endothelial growth factor receptor 2 CHEMBL279	IC50	8.82	8.53	1.5	8
Vascular endothelial growth factor receptor 2 CHEMBL279	Ki	8.82	8.82	1.5	1
Receptor-interacting serine/threonine-protein kinase 3 CHEMBL1795199	IC50	8.8	8.1475	1.6	4
Mast/stem cell growth factor receptor Kit CHEMBL1936	IC50	8.77	8.04	1.7	7
CGTH-W-1 CHEMBL2366300	IC50	8.77	8.77	1.7	1
Fibroblast growth factor receptor CHEMBL2095217	IC50	8.66	8.66	2.2	1
Kasumi 1 CHEMBL613988	IC50	8.66	8.66	2.2	1
Proto-oncogene tyrosine-protein kinase Src CHEMBL267	IC50	8.6	8.3143	2.5	7
BE-13 CHEMBL2366303	IC50	8.59	8.59	2.6	1
Vascular endothelial growth factor receptor 1 CHEMBL1868	IC50	8.43	8.055	3.7	2
CTV-1 CHEMBL2366360	IC50	8.28	8.28	5.2	1
NKM-1 CHEMBL2366133	IC50	8.18	8.18	6.5	1
Receptor-type tyrosine-protein kinase FLT3 CHEMBL1974	Kd	8.15	8.15	7.0	1
Fibroblast growth factor receptor 4 CHEMBL3973	IC50	8.15	7.8733	7.1	3
ADMET CHEMBL612558	IC50	8.14	6.93	7.3	2
Ephrin type-A receptor 5 CHEMBL3987	Kd	8.1	8.1	8.0	1
MONO-MAC-6 CHEMBL2366062	IC50	8.08	8.08	8.4	1
Macrophage colony-stimulating factor 1 receptor CHEMBL1844	IC50	8.07	8.07	8.6	1
Fibroblast growth factor receptor 3 CHEMBL2742	IC50	8.03	7.89	9.4	2
Epithelial discoidin domain-containing receptor 1 CHEMBL5319	IC50	8.03	8.03	9.4	1
KBM5 CHEMBL4483250	IC50	7.99	7.98	10.2	2
Protein cereblon/BCR/ABL CHEMBL4296137	EC50	7.97	7.97	10.6	1
High affinity nerve growth factor receptor CHEMBL2815	IC50	7.94	7.55	11.4	2
Receptor-interacting serine/threonine-protein kinase 1 CHEMBL5464	IC50	7.92	7.92	12.0	2

Pharmacokinetic Data

Parameter	Value	Units	Species
AUC	278.5	ng.hr/ml/mg/kg	Rattus norvegicus
AUC	13710.0	ng.hr.mL-1	Rattus norvegicus
AUC	2086.0	ng.hr.mL-1	Rattus norvegicus
AUC	995.0	ng.hr.mL-1	Rattus norvegicus
AUC	363.0	ng.hr.mL-1	Mus musculus
AUC	497.0	ng.hr.mL-1	Mus musculus
AUC	432.0	ng.hr.mL-1	Mus musculus
AUC	528.0	ng.hr.mL-1	Mus musculus
AUC	1.0	-	Homo sapiens
CL	10.83	mL.min-1.kg-1	Rattus norvegicus
CL	4.68	uL.min-1.(10^6cells)-1	Rattus norvegicus
CL	3.0	uL.min-1.(10^6cells)-1	Homo sapiens
CL	1.0	mL.min-1.g-1	Homo sapiens
CL	18.0	mL.min-1.g-1	Mus musculus
CL	161.33	mL.min-1.kg-1	Mus musculus
Cmax	384.55	nM	Rattus norvegicus
Cmax	2491.69	nM	Rattus norvegicus
Cmax	394.13	nM	Rattus norvegicus
Cmax	230.39	nM	Rattus norvegicus
Cmax	131.44	nM	Mus musculus
Cmax	506.98	nM	Mus musculus
F	18.2	%	Rattus norvegicus
F	27.0	%	Mus musculus
MRT	5.25	hr	Mus musculus
MRT	4.29	hr	Mus musculus
T1/2	10.2	hr	Rattus norvegicus
T1/2	11.0	hr	Rattus norvegicus
T1/2	2.4	hr	Rattus norvegicus
T1/2	3.2	hr	Rattus norvegicus
T1/2	3.2	hr	Rattus norvegicus

Activity Data Samples

Top measurements by pChEMBL value

Target	Type	Rel.	Value	Units	pChEMBL	Assay	PubMed
Bcr/Abl fusion protein	EC50	=	0.05	nM	10.3	Inhibition of human wild type BCR-ABL expressed in mouse BAF3 cells assessed as ...	27010810
MV4-11	IC50	=	0.09555	nM	10.02	SANGER: Inhibition of human MV-4-11 cell growth in a cell viability assay.	-
KU812 cell line	IC50	=	0.1	nM	10.0	Cytotoxicity against human KU812 cells assessed as inhibition of cell growth mea...	34011155
Tyrosine-protein kinase HCK	IC50	=	0.11	nM	9.96	Binding affinity to human HCK using KVEKIGEGTYGVVYK as substrate by radiometric ...	29937980
MEG-01	IC50	=	0.1276	nM	9.89	SANGER: Inhibition of human MEG-01 cell growth in a cell viability assay.	-
Tyrosine-protein kinase Lyn	IC50	=	0.16	nM	9.8	Binding affinity to LYN (unknown origin)	29937980
LAMA-84	IC50	=	0.1653	nM	9.78	SANGER: Inhibition of human LAMA-84 cell growth in a cell viability assay.	-
Tyrosine-protein kinase Lyn	IC50	=	0.24	nM	9.62	Inhibition of recombinant human Lyn using peptide substrate poly[Glu:Tyr] (4:1) ...	27914362
Tyrosine-protein kinase Lck	IC50	=	0.28	nM	9.55	Binding affinity to human LCK using poly[Glu:Tyr] (4:1) as substrate by radiomet...	29937980
Bcr/Abl fusion protein	EC50	=	0.3	nM	9.52	Inhibition of human BCR-ABL T315I mutant expressed in mouse BAF3 cells assessed ...	27010810
Receptor-type tyrosine-protein kinase FLT3	IC50	=	0.3	nM	9.52	Inhibition of FLT3 (unknown origin) by kinase hotspot assay	34402300
K562	IC50	=	0.3	nM	9.52	Cytotoxicity against human K562 cells assessed as cell growth inhibition measure...	34011155
Tyrosine-protein kinase ABL1	IC50	=	0.3	nM	9.52	Inhibition of wild type human ABL Q252H mutant using [EAIYAAPFAKKK] as substrate...	32432477
Tyrosine-protein kinase ABL1	IC50	=	0.3	nM	9.52	Inhibition of wild type human ABL Y253F mutant using [EAIYAAPFAKKK] as substrate...	32432477
Tyrosine-protein kinase ABL1	IC50	=	0.3	nM	9.52	Inhibition of wild type human ABL M351T mutant using [EAIYAAPFAKKK] as substrate...	32432477
Tyrosine-protein kinase ABL1	IC50	=	0.3	nM	9.52	Inhibition of wild type human ABL H396P mutant using [EAIYAAPFAKKK] as substrate...	32432477
K562	IC50	=	0.3	nM	9.52	Antiproliferative activity against human K562 cells incubated for 3 days by CCK8...	32657579
Proto-oncogene tyrosine-protein kinase receptor Ret	IC50	=	0.3	nM	9.52	Inhibition of recombinant RET (unknown origin) using poly (Glu,Tyr) 4:1 as subst...	27750146
Receptor-type tyrosine-protein kinase FLT3	IC50	=	0.3	nM	9.52	Inhibition of FLT3 in human MV4-11 cells	-
Tyrosine-protein kinase ABL1	IC50	=	0.31	nM	9.51	Inhibition of human ABL1 assessed as residual activity using EAIYAAPFAKKK as sub...	32292555

Literature References

PubMed	DOI	Target Context	# Activities
20513156	10.1021/jm100395q	Rattus norvegicus	20
34011155	10.1021/acs.jmedchem.1c00082	ADMET	15
20513156	10.1021/jm100395q	BaF3	12
34011155	10.1021/acs.jmedchem.1c00082	Tyrosine-protein kinase ABL1	10
30137981	10.1021/acs.jmedchem.8b01040	Bcr/Abl fusion protein	10
20513156	10.1021/jm100395q	Unchecked	9
20513156	10.1021/jm100395q	Tyrosine-protein kinase ABL1	9
23301703	10.1021/jm301581y	Tyrosine-protein kinase ABL1	8
32432477	10.1021/acs.jmedchem.0c00507	Tyrosine-protein kinase ABL1	6
26254279	10.18632/oncotarget.4214	Unchecked	6
23773153	10.1021/jm4004076	NON-PROTEIN TARGET	6
28991465	10.1021/acs.jmedchem.7b00841	Mast/stem cell growth factor receptor Kit	5
28287083	10.1038/ncomms14768	Unchecked	5
29191878	10.1126/science.aan4368	Unchecked	5
-	10.6019/CHEMBL4651402	SARS-CoV-2	4
27750146	10.1016/j.ejmech.2016.10.003	BaF3	4
34011155	10.1021/acs.jmedchem.1c00082	BaF3	4
29937980	10.1021/acsmedchemlett.8b00081	Tyrosine-protein kinase JAK2	4
-	10.6019/CHEMBL4495565	SARS-CoV-2	4
37849551	10.1021/acsmedchemlett.3c00389	Bcr/Abl fusion protein	4

Data from ChEMBL 36 via Core Engine