Molecule Details
| InChIKey | PHXJVRSECIGDHY-UHFFFAOYSA-N |
|---|---|
| Compound Name | Ponatinib |
| Canonical SMILES | Cc1ccc(C(=O)Nc2ccc(CN3CCN(C)CC3)c(C(F)(F)F)c2)cc1C#Cc1cnc2cccnn12 |
| Clinical Status | Data-mined Candidate |
| Targets (Human+Pathogen) | 59 |
| Pfam Stratification | Cross-Family |
| Avg pChEMBL | 7.67 |
| Source | BindingDB;ChEMBL |
2D Structure
Activity Profile
DrugBank Annotations
| DrugBank ID | DB08901 |
|---|---|
| Drug Name | Ponatinib |
| CAS Number | 943319-70-8 |
| Groups | approved investigational |
| ATC Codes | L01EA05 |
| Description | Ponatinib is a novel Bcr-Abl tyrosine kinase inhibitor that is especially effective against the T315I mutation for the treatment of chronic myeloid leukemia. FDA approved on December 14, 2012. |
Categories: Antineoplastic Agents Antineoplastic and Immunomodulating Agents BCRP/ABCG2 Inhibitors BCRP/ABCG2 Substrates Bcr-Abl Tyrosine Kinase Inhibitors Cytochrome P-450 CYP2C8 Substrates Cytochrome P-450 CYP2C8 Substrates with a Narrow Therapeutic Index Cytochrome P-450 CYP2D6 Substrates Cytochrome P-450 CYP2D6 Substrates with a Narrow Therapeutic Index Cytochrome P-450 CYP3A Substrates Cytochrome P-450 CYP3A4 Substrates Cytochrome P-450 CYP3A4 Substrates with a Narrow Therapeutic Index Cytochrome P-450 CYP3A5 Substrates Cytochrome P-450 CYP3A5 Substrates with a Narrow Therapeutic Index Cytochrome P-450 Substrates Enzyme Inhibitors Hepatotoxic Agents Immunosuppressive Agents Kinase Inhibitor Myelosuppressive Agents Narrow Therapeutic Index Drugs P-glycoprotein inhibitors P-glycoprotein substrates P-glycoprotein substrates with a Narrow Therapeutic Index Protein Kinase Inhibitors Tyrosine Kinase Inhibitors
Cross-references: BindingDB: 50322535 ChEBI: 78543 CHEMBL1171837 ChemSpider: 24747381 Drugs Product Database (DPD): 22576 D09950 PDB: 0LI PharmGKB: PA165980594 PubChem:24826799 PubChem:175427142 RxCUI: 1364347 Wikipedia: Ponatinib ZINC: ZINC000036701290
Target Activities (59)
| Target | Gene | Organism | Category | Pfam | pChEMBL | Type | Source |
|---|---|---|---|---|---|---|---|
| P08631 | HCK | Homo sapiens | Human | PF07714 PF00017 PF00018 | 10.0 | IC50 | ChEMBL;BindingDB |
| P07948 | LYN | Homo sapiens | Human | PF07714 PF00017 PF00018 | 9.6 | IC50 | ChEMBL;BindingDB |
| P06239 | LCK | Homo sapiens | Human | PF07714 PF00017 PF00018 | 9.6 | IC50 | ChEMBL;BindingDB |
| P06241 | FYN | Homo sapiens | Human | PF07714 PF00017 PF00018 | 9.4 | IC50 | ChEMBL;BindingDB |
| P00519 | ABL1 | Homo sapiens | Human | PF08919 PF07714 PF00017 PF00018 | 9.1 | IC50 | ChEMBL;BindingDB |
| P07947 | YES1 | Homo sapiens | Human | PF07714 PF00017 PF00018 | 9.1 | IC50 | ChEMBL;BindingDB |
| P11274 | BCR | Homo sapiens | Human | PF09036 PF00168 PF19057 PF00620 PF00621 | 9.0 | IC50 | ChEMBL |
| P16234 | PDGFRA | Homo sapiens | Human | PF07679 PF25305 PF07714 | 9.0 | IC50 | ChEMBL;BindingDB |
| P09619 | PDGFRB | Homo sapiens | Human | PF00047 PF13927 PF25305 PF07714 | 8.9 | IC50 | ChEMBL;BindingDB |
| P42685 | FRK | Homo sapiens | Human | PF07714 PF00017 PF00018 | 8.9 | IC50 | ChEMBL;BindingDB |
| Q9Y572 | RIPK3 | Homo sapiens | Human | PF00069 PF12721 | 8.8 | IC50 | ChEMBL;BindingDB |
| P35968 | KDR | Homo sapiens | Human | PF07679 PF00047 PF13895 PF22971 PF07714 PF21339 PF17988 PF22854 | 8.8 | IC50 | ChEMBL;BindingDB |
| P11362 | FGFR1 | Homo sapiens | Human | PF07679 PF00047 PF07714 | 8.7 | IC50 | ChEMBL;BindingDB |
| P21802 | FGFR2 | Homo sapiens | Human | PF07679 PF13927 PF07714 | 8.7 | IC50 | ChEMBL;BindingDB |
| P12931 | SRC | Homo sapiens | Human | PF07714 PF00017 PF00018 | 8.3 | IC50 | ChEMBL;BindingDB |
| P10721 | KIT | Homo sapiens | Human | PF00047 PF07714 | 8.2 | IC50 | ChEMBL;BindingDB |
| O43353 | RIPK2 | Homo sapiens | Human | PF00619 PF07714 | 8.2 | IC50 | ChEMBL;BindingDB |
| P29317 | EPHA2 | Homo sapiens | Human | PF14575 PF25599 PF01404 PF00041 PF07714 PF00536 | 8.2 | Kd | ChEMBL;BindingDB |
| P22455 | FGFR4 | Homo sapiens | Human | PF07679 PF13927 PF07714 | 8.1 | IC50 | ChEMBL;BindingDB |
| P54756 | EPHA5 | Homo sapiens | Human | PF14575 PF25599 PF01404 PF00041 PF07714 PF00536 | 8.1 | Kd | ChEMBL |
| P07333 | CSF1R | Homo sapiens | Human | PF00047 PF25305 PF07714 | 8.1 | IC50 | ChEMBL;BindingDB |
| P17948 | FLT1 | Homo sapiens | Human | PF07679 PF00047 PF13927 PF22971 PF07714 PF21339 PF17988 PF22854 | 8.1 | IC50 | ChEMBL;BindingDB |
| P22607 | FGFR3 | Homo sapiens | Human | PF21165 PF07679 PF13927 PF07714 | 8.0 | IC50 | ChEMBL;BindingDB |
| Q08345 | DDR1 | Homo sapiens | Human | PF21114 PF00754 PF07714 | 8.0 | IC50 | ChEMBL;BindingDB |
| Q13546 | RIPK1 | Homo sapiens | Human | PF00531 PF07714 | 7.9 | IC50 | ChEMBL;BindingDB |
| P36888 | FLT3 | Homo sapiens | Human | PF00047 PF07714 | 7.9 | IC50 | ChEMBL;BindingDB |
| P41240 | CSK | Homo sapiens | Human | PF07714 PF00017 PF00018 | 7.9 | IC50 | ChEMBL;BindingDB |
| P15056 | BRAF | Homo sapiens | Human | PF00130 PF07714 PF02196 | 7.8 | IC50 | BindingDB |
| P49336 | CDK8 | Homo sapiens | Human | PF00069 | 7.8 | IC50 | ChEMBL |
| P42684 | ABL2 | Homo sapiens | Human | PF08919 PF07714 PF00017 PF00018 | 7.7 | Kd | ChEMBL |
| P07949 | RET | Homo sapiens | Human | PF00028 PF07714 PF17756 PF17812 PF17813 PF22540 | 7.6 | IC50 | ChEMBL;BindingDB |
| P04629 | NTRK1 | Homo sapiens | Human | PF13855 PF16920 PF07714 PF18613 | 7.5 | IC50 | ChEMBL |
| P23458 | JAK1 | Homo sapiens | Human | PF18379 PF18377 PF17887 PF07714 PF21990 | 7.5 | IC50 | ChEMBL;BindingDB |
| P09769 | FGR | Homo sapiens | Human | PF07714 PF00017 PF00018 | 7.4 | Kd | ChEMBL |
| Q9UNQ0 | ABCG2 | Homo sapiens | Human | PF01061 PF19055 PF00005 | 7.4 | IC50 | ChEMBL;BindingDB |
| Q12851 | MAP4K2 | Homo sapiens | Human | PF00780 PF00069 | 7.4 | Kd | ChEMBL |
| Q9NYL2 | MAP3K20 | Homo sapiens | Human | PF07714 PF07647 | 7.4 | Kd | ChEMBL |
| Q9NWZ3 | IRAK4 | Homo sapiens | Human | PF07714 | 7.2 | IC50 | ChEMBL |
| Q13470 | TNK1 | Homo sapiens | Human | PF07714 PF22931 | 7.1 | Kd | ChEMBL |
| Q92499 | DDX1 | Homo sapiens | Human | PF00270 PF00271 PF00622 | 7.1 | Kd | ChEMBL |
| Q16832 | DDR2 | Homo sapiens | Human | PF21114 PF00754 PF07714 | 7.1 | Kd | ChEMBL |
| Q15746 | MYLK | Homo sapiens | Human | PF16620 PF00041 PF07679 PF00069 | 7.0 | Kd | ChEMBL |
| P21709 | EPHA1 | Homo sapiens | Human | PF14575 PF25599 PF01404 PF07699 PF00041 PF07714 PF00536 | 6.8 | IC50 | ChEMBL;BindingDB |
| Q16539 | MAPK14 | Homo sapiens | Human | PF00069 | 6.8 | Kd | ChEMBL |
| O60674 | JAK2 | Homo sapiens | Human | PF18379 PF18377 PF17887 PF07714 PF21990 | 6.8 | IC50 | ChEMBL;BindingDB |
| Q16204 | CCDC6 | Homo sapiens | Human | PF09755 | 6.7 | IC50 | ChEMBL |
| Q5S007 | LRRK2 | Homo sapiens | Human | PF23745 PF23744 PF23748 PF16095 PF25497 PF13855 PF00069 PF08477 | 6.7 | IC50 | ChEMBL;BindingDB |
| Q14289 | PTK2B | Homo sapiens | Human | PF21477 PF00373 PF18038 PF03623 PF07714 | 6.5 | Kd | ChEMBL |
| O95819 | MAP4K4 | Homo sapiens | Human | PF00780 PF00069 | 6.5 | Kd | ChEMBL |
| Q00537 | CDK17 | Homo sapiens | Human | PF00069 | 6.5 | Kd | ChEMBL |
| Q9UKE5 | TNIK | Homo sapiens | Human | PF00780 PF00069 | 6.4 | Kd | ChEMBL |
| P49137 | MAPKAPK2 | Homo sapiens | Human | PF00069 | 6.3 | Kd | ChEMBL |
| Q13233 | MAP3K1 | Homo sapiens | Human | PF21040 PF00069 PF04434 | 6.3 | Kd | ChEMBL |
| P54753 | EPHB3 | Homo sapiens | Human | PF14575 PF25599 PF01404 PF07699 PF00041 PF07714 PF00536 | 6.3 | Kd | ChEMBL |
| P17612 | PRKACA | Homo sapiens | Human | PF00069 | 6.2 | IC50 | ChEMBL;BindingDB |
| P51617 | IRAK1 | Homo sapiens | Human | PF00531 PF00069 | 6.2 | Kd | ChEMBL |
| Q12809 | KCNH2 | Homo sapiens | Human | PF00027 PF00520 PF13426 | 6.1 | IC50 | ChEMBL;BindingDB |
| Q92918 | MAP4K1 | Homo sapiens | Human | PF00780 PF00069 | 6.1 | Kd | ChEMBL |
| Q15759 | MAPK11 | Homo sapiens | Human | PF00069 | 6.0 | Kd | ChEMBL |
DrugBank Target Actions (23)
| Target | Gene | Target Name | Action | Type |
|---|---|---|---|---|
| P08684 | CYP3A4 | Cytochrome P450 3A4 | substrate | enzymes |
| P10632 | CYP2C8 | Cytochrome P450 2C8 | substrate | enzymes |
| P10635 | CYP2D6 | Cytochrome P450 2D6 | substrate | enzymes |
| P20815 | CYP3A5 | Cytochrome P450 3A5 | substrate | enzymes |
| P00519 | ABL1 | Tyrosine-protein kinase ABL1 | inhibitor | targets |
| P06239 | LCK | Tyrosine-protein kinase Lck | inhibitor | targets |
| P07948 | LYN | Tyrosine-protein kinase Lyn | inhibitor | targets |
| P07949 | RET | Proto-oncogene tyrosine-protein kinase receptor Ret | inhibitor | targets |
| P10721 | KIT | Mast/stem cell growth factor receptor Kit | inhibitor | targets |
| P11274 | BCR | Breakpoint cluster region protein | inhibitor | targets |
| P11362 | FGFR1 | Fibroblast growth factor receptor 1 | inhibitor | targets |
| P12931 | SRC | Proto-oncogene tyrosine-protein kinase Src | inhibitor | targets |
| P16234 | PDGFRA | Platelet-derived growth factor receptor alpha | inhibitor | targets |
| P21802 | FGFR2 | Fibroblast growth factor receptor 2 | inhibitor | targets |
| P22455 | FGFR4 | Fibroblast growth factor receptor 4 | inhibitor | targets |
| P22607 | FGFR3 | Fibroblast growth factor receptor 3 | inhibitor | targets |
| P35968 | KDR | Vascular endothelial growth factor receptor 2 | inhibitor | targets |
| P36888 | FLT3 | Receptor-type tyrosine-protein kinase FLT3 | inhibitor | targets |
| Q02763 | TEK | Angiopoietin-1 receptor | inhibitor | targets |
| P08183 | ABCB1 | ATP-dependent translocase ABCB1 | inhibitor | transporters |
| Q9UNQ0 | ABCG2 | Broad substrate specificity ATP-binding cassette transporter ABCG2 | inhibitor | transporters |
| P08183 | ABCB1 | ATP-dependent translocase ABCB1 | substrate | transporters |
| Q9UNQ0 | ABCG2 | Broad substrate specificity ATP-binding cassette transporter ABCG2 | substrate | transporters |