Drug Details
| General Information of the Drug (ID: DR8026) | ||||
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| Name |
Ponatinib
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| Synonyms |
Iclusig (TN)
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| Molecular Type |
Small molecule
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| Disease | Mantle cell lymphoma [ICD-11: 2A85] | Approved | [1] | |
| Structure |
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Click to Download Mol2D MOL |
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| ADMET Property |
Half-life
The concentration or amount of drug in body reduced by one-half in 24 hours (in cancer patients with 45 mg ponatinib once daily)
Metabolism
The drug is metabolized via the esterases and/or amidases
Vd
The volume of distribution (Vd) of drug is 1223 L
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| Click to Show/Hide the Molecular Information and External Link(s) of This Natural Product | ||||
| Formula |
C29H27F3N6O
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| PubChem CID | ||||
| Canonical SMILES |
CC1=C(C=C(C=C1)C(=O)NC2=CC(=C(C=C2)CN3CCN(CC3)C)C(F)(F)F)C#CC4=CN=C5N4N=CC=C5
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| InChI |
1S/C29H27F3N6O/c1-20-5-6-22(16-21(20)8-10-25-18-33-27-4-3-11-34-38(25)27)28(39)35-24-9-7-23(26(17-24)29(30,31)32)19-37-14-12-36(2)13-15-37/h3-7,9,11,16-18H,12-15,19H2,1-2H3,(H,35,39)
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| InChIKey |
PHXJVRSECIGDHY-UHFFFAOYSA-N
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| CAS Number |
CAS 943319-70-8
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| GDSC | ||||
| TTD Drug ID | ||||
| DrugBank ID | ||||
| Combinatorial Therapeutic Effect(s) Validated Clinically or Experimentally | ||||||
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| α. A List of Natural Product(s) Able to Enhance the Efficacy of This Drug | ||||||
| Epigallocatechin gallate | Hamamelis virginiana | Click to Show/Hide the Molecular Data of This NP | ||||
| Achieving Therapeutic Synergy | Click to Show/Hide | |||||
| Representative Experiment Reporting the Effect of This Combination | [2] | |||||
| Detail(s) |
Combination Info
click to show the detail info of this combination
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| Molecule(s)
Regulation |
Down-regulation | Expression | CCND1 | Molecule Info |
Pathway MAP
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| Down-regulation | Expression | MPIP1 | Molecule Info |
Pathway MAP
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| Up-regulation | Expression | TGFB2 | Molecule Info |
Pathway MAP
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| In-vitro Model | K-562 | CVCL_0004 | Chronic myelogenous leukemia | Homo sapiens | ||
| Experimental
Result(s) |
Synergistic effect of ponatinib and epigallocatechin-3-gallate induces apoptosis in chronic myeloid leukemia cells through altering expressions of cell cycle regulatory genes. | |||||
| Forskolin | Plectranthus barbatus | Click to Show/Hide the Molecular Data of This NP | ||||
| Achieving Therapeutic Synergy | Click to Show/Hide | |||||
| Representative Experiment Reporting the Effect of This Combination | [3] | |||||
| Detail(s) |
Combination Info
click to show the detail info of this combination
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| Molecule(s)
Regulation |
Down-regulation | Phosphorylation | BRD4 | Molecule Info |
Pathway MAP
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| Down-regulation | Phosphorylation | CRKL | Molecule Info |
Pathway MAP
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| In-vitro Model | KCL-22 | CVCL_2091 | Chronic myelogenous leukemia | Homo sapiens | ||
| K-562 | CVCL_0004 | Chronic myelogenous leukemia | Homo sapiens | |||
| HH [Human lymphoma] | CVCL_1280 | Cutaneous T-cell non-Hodgkin lymphoma | Homo sapiens | |||
| HEK293 | CVCL_0045 | Healthy | Homo sapiens | |||
| Hep-G2 | CVCL_0027 | Hepatocellular carcinoma | Homo sapiens | |||
| Human peripheral blood mononuclear cells | Healthy | Homo sapiens | ||||
| Experimental
Result(s) |
A synergistic combination of ponatinib- and forskolin-reduced cell viability was identified in this clinically relevant imatinib-resistant CML cell line, which also proved efficacious in other CML cell lines. | |||||
| Target and Pathway | ||||
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| Target(s) | Fms-like tyrosine kinase 3 (FLT-3) | Molecule Info | [4] | |
| Proto-oncogene c-Ret (RET) | Molecule Info | [4] | ||
| Tyrosine-protein kinase ABL1 (ABL) | Molecule Info | [4] | ||
| Tyrosine-protein kinase Kit (KIT) | Molecule Info | [4] | ||
| KEGG Pathway | ErbB signaling pathway | Click to Show/Hide | ||
| 2 | Ras signaling pathway | |||
| 3 | Cell cycle | |||
| 4 | Axon guidance | |||
| 5 | Neurotrophin signaling pathway | |||
| 6 | Pathogenic Escherichia coli infection | |||
| 7 | Shigellosis | |||
| 8 | Pathways in cancer | |||
| 9 | MicroRNAs in cancer | |||
| 10 | Chronic myeloid leukemia | |||
| 11 | Viral myocarditis | |||
| 12 | Cytokine-cytokine receptor interaction | |||
| 13 | Hematopoietic cell lineage | |||
| 14 | Transcriptional misregulation in cancer | |||
| 15 | Acute myeloid leukemia | |||
| 16 | Central carbon metabolism in cancer | |||
| 17 | Rap1 signaling pathway | |||
| 18 | Endocytosis | |||
| 19 | PI3K-Akt signaling pathway | |||
| 20 | Melanogenesis | |||
| 21 | Thyroid cancer | |||
| NetPath Pathway | IL3 Signaling Pathway | Click to Show/Hide | ||
| 2 | IL4 Signaling Pathway | |||
| 3 | KitReceptor Signaling Pathway | |||
| Panther Pathway | Axon guidance mediated by Slit/Robo | Click to Show/Hide | ||
| Pathway Interaction Database | p73 transcription factor network | Click to Show/Hide | ||
| 2 | ATM pathway | |||
| 3 | Regulation of Telomerase | |||
| 4 | Posttranslational regulation of adherens junction stability and dissassembly | |||
| 5 | Lissencephaly gene (LIS1) in neuronal migration and development | |||
| 6 | PDGFR-beta signaling pathway | |||
| 7 | Neurotrophic factor-mediated Trk receptor signaling | |||
| 8 | Validated transcriptional targets of TAp63 isoforms | |||
| 9 | p53 pathway | |||
| 10 | Regulation of retinoblastoma protein | |||
| 11 | C-MYB transcription factor network | |||
| 12 | Signaling events mediated by Stem cell factor receptor (c-Kit) | |||
| 13 | Signaling events regulated by Ret tyrosine kinase | |||
| Reactome | Regulation of actin dynamics for phagocytic cup formation | Click to Show/Hide | ||
| 2 | CDO in myogenesis | |||
| 3 | RHO GTPases Activate WASPs and WAVEs | |||
| 4 | HDR through Single Strand Annealing (SSA) | |||
| 5 | Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks | |||
| 6 | Factors involved in megakaryocyte development and platelet production | |||
| 7 | PIP3 activates AKT signaling | |||
| 8 | Regulation of KIT signaling | |||
| 9 | Constitutive Signaling by Aberrant PI3K in Cancer | |||
| 10 | RAF/MAP kinase cascade | |||
| WikiPathways | Apoptosis-related network due to altered Notch3 in ovarian cancer | Click to Show/Hide | ||
| 2 | Fcgamma receptor (FCGR) dependent phagocytosis | |||
| 3 | ATM Signaling Pathway | |||
| 4 | Retinoblastoma (RB) in Cancer | |||
| 5 | Integrated Pancreatic Cancer Pathway | |||
| 6 | Pathogenic Escherichia coli infection | |||
| 7 | Regulation of Microtubule Cytoskeleton | |||
| 8 | Integrated Breast Cancer Pathway | |||
| 9 | Signaling by Robo receptor | |||
| 10 | Myogenesis | |||
| 11 | Factors involved in megakaryocyte development and platelet production | |||
| 12 | Kit receptor signaling pathway | |||
| 13 | Differentiation Pathway | |||
| 14 | Signaling by SCF-KIT | |||
| 15 | PIP3 activates AKT signaling | |||
| 16 | Cardiac Progenitor Differentiation | |||
| 17 | miR-targeted genes in muscle cell - TarBase | |||
| 18 | miR-targeted genes in lymphocytes - TarBase | |||
| 19 | miR-targeted genes in epithelium - TarBase | |||
| 20 | SIDS Susceptibility Pathways | |||
| 21 | Dopaminergic Neurogenesis | |||
