Drug Details
| General Information of the Drug (ID: DR6385) | ||||
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| Name |
Nutlin-3
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| Synonyms |
nutlin-3A; nutlin 3; (+/-)-Nutlin3; CHEMBL211045; Nutlin 3(Random Configuration); MDM2 Antagonist, Nutlin-3, Racemic; 4-(4,5-bis(4-chlorophenyl)-2-(2-isopropoxy-4-methoxyphenyl)-4,5-dihydro-1H-imidazole-1-carbonyl)piperazin-2-one; 4-({4,5-bis(4-chlorophenyl)-2-[4-methoxy-2-(propan-2-yloxy)phenyl]-4,5-dihydro-1H-imidazol-1-yl}carbonyl)piperazin-2-one; 4-[4,5-bis(4-chlorophenyl)-2-(4-methoxy-2-propan-2-yloxyphenyl)-4,5-dihydroimidazole-1-carbonyl]piperazin-2-one; 548472-68-0; 890090-75-2
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| Molecular Type |
Small molecule
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| Disease | Lung cancer [ICD-11: 2C25] | Investigative | [1] | |
| Structure |
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Click to Download Mol2D MOL |
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| Click to Show/Hide the Molecular Information and External Link(s) of This Natural Product | ||||
| Formula |
C30H30Cl2N4O4
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| PubChem CID | ||||
| Canonical SMILES |
CC(C)OC1=C(C=CC(=C1)OC)C2=NC(C(N2C(=O)N3CCNC(=O)C3)C4=CC=C(C=C4)Cl)C5=CC=C(C=C5)Cl
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| InChI |
1S/C30H30Cl2N4O4/c1-18(2)40-25-16-23(39-3)12-13-24(25)29-34-27(19-4-8-21(31)9-5-19)28(20-6-10-22(32)11-7-20)36(29)30(38)35-15-14-33-26(37)17-35/h4-13,16,18,27-28H,14-15,17H2,1-3H3,(H,33,37)
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| InChIKey |
BDUHCSBCVGXTJM-UHFFFAOYSA-N
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| CAS Number |
CAS 548472-68-0
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| GDSC | ||||
| TTD Drug 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 | ||||||
| Resveratrol | Gnetum parvifolium | 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
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| Molecule(s)
Regulation |
Up-regulation | Activity | CASP3 | Molecule Info |
Pathway MAP
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| Biological
Regulation |
Up-regulation | Cytochrome c release | ||||
| In-vitro Model | A2780 | CVCL_0134 | Ovarian endometrioid adenocarcinoma | Homo sapiens | ||
| A2780/CP70 | CVCL_0135 | Ovarian endometrioid adenocarcinoma | Homo sapiens | |||
| Experimental
Result(s) |
Treatment of ovarian cancer cells with nutlin-3 and resveratrol combination leads to apoptosis via caspase activation. | |||||
| Tanshinone IIA | Salvia miltiorrhiza | 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 | Expression | AKT1 | Molecule Info |
Pathway MAP
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| Down-regulation | Expression | mTOR | Molecule Info |
Pathway MAP
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| In-vitro Model | SUP-B15 | CVCL_0103 | B acute lymphoblastic leukemia | Homo sapiens | ||
| NALM-6 | CVCL_0092 | Adult B acute lymphoblastic leukemia | Homo sapiens | |||
| HL-60 | CVCL_0002 | Adult acute myeloid leukemia | Homo sapiens | |||
| MV4-11 | CVCL_0064 | Childhood acute monocytic leukemia | Homo sapiens | |||
| Experimental
Result(s) |
The combination of Nutlin-3 and Tanshinone IIA exerts synergistic anti-leukemia effects by regulating the p53 and AKT/mTOR pathways. | |||||
| Target and Pathway | ||||
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| Target(s) | Ubiquitin-protein ligase E3 Mdm2 (MDM2) | Molecule Info | [4] | |
| KEGG Pathway | FoxO signaling pathway | Click to Show/Hide | ||
| 2 | Cell cycle | |||
| 3 | p53 signaling pathway | |||
| 4 | Ubiquitin mediated proteolysis | |||
| 5 | Endocytosis | |||
| 6 | PI3K-Akt signaling pathway | |||
| 7 | Thyroid hormone signaling pathway | |||
| 8 | Epstein-Barr virus infection | |||
| 9 | Pathways in cancer | |||
| 10 | Transcriptional misregulation in cancer | |||
| 11 | Viral carcinogenesis | |||
| 12 | Proteoglycans in cancer | |||
| 13 | MicroRNAs in cancer | |||
| 14 | Glioma | |||
| 15 | Prostate cancer | |||
| 16 | Melanoma | |||
| 17 | Bladder cancer | |||
| 18 | Chronic myeloid leukemia | |||
| Panther Pathway | Insulin/IGF pathway-protein kinase B signaling cascade | Click to Show/Hide | ||
| 2 | p53 pathway | |||
| 3 | Ubiquitin proteasome pathway | |||
| 4 | P53 pathway feedback loops 1 | |||
| 5 | p53 pathway feedback loops 2 | |||
| Pathway Interaction Database | ErbB4 signaling events | Click to Show/Hide | ||
| 2 | p73 transcription factor network | |||
| 3 | ATR signaling pathway | |||
| 4 | ATM pathway | |||
| 5 | Glucocorticoid receptor regulatory network | |||
| 6 | Sumoylation by RanBP2 regulates transcriptional repression | |||
| 7 | Direct p53 effectors | |||
| 8 | Regulation of Androgen receptor activity | |||
| 9 | Validated transcriptional targets of deltaNp63 isoforms | |||
| 10 | Aurora A signaling | |||
| 11 | Validated transcriptional targets of TAp63 isoforms | |||
| 12 | p53 pathway | |||
| 13 | Regulation of retinoblastoma protein | |||
| Reactome | AKT phosphorylates targets in the cytosol | Click to Show/Hide | ||
| 2 | Oxidative Stress Induced Senescence | |||
| 3 | Oncogene Induced Senescence | |||
| 4 | Trafficking of AMPA receptors | |||
| 5 | Constitutive Signaling by AKT1 E17K in Cancer | |||
| 6 | Stabilization of p53 | |||
| WikiPathways | DNA Damage Response (only ATM dependent) | Click to Show/Hide | ||
| 2 | DNA Damage Response | |||
| 3 | Senescence and Autophagy in Cancer | |||
| 4 | Tryptophan metabolism | |||
| 5 | G1 to S cell cycle control | |||
| 6 | Copper homeostasis | |||
| 7 | Bladder Cancer | |||
| 8 | Neurotransmitter Receptor Binding And Downstream Transmission In The Postsynaptic Cell | |||
| 9 | PIP3 activates AKT signaling | |||
| 10 | Apoptosis | |||
| 11 | ATM Signaling Pathway | |||
| 12 | Retinoblastoma (RB) in Cancer | |||
| 13 | Integrated Pancreatic Cancer Pathway | |||
| 14 | Prostate Cancer | |||
| 15 | Signaling Pathways in Glioblastoma | |||
| 16 | Integrated Breast Cancer Pathway | |||
| 17 | Integrated Cancer pathway | |||
| 18 | Cell Cycle | |||
| 19 | Cell Cycle Checkpoints | |||
| 20 | TP53 Network | |||
| 21 | miRNA Regulation of DNA Damage Response | |||
| 22 | Androgen receptor signaling pathway | |||
