Drug Details
| General Information of the Drug (ID: DR9921) | ||||
|---|---|---|---|---|
| Name |
Tumor necrosis factor alpha
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| Molecular Type |
Protein
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| Disease | Colorectal cancer [ICD-11: 2B91] | Phase 2 | [1] | |
| Combinatorial Therapeutic Effect(s) Validated Clinically or Experimentally | ||||||
|---|---|---|---|---|---|---|
| α. A List of Natural Product(s) Able to Enhance the Efficacy of This Drug | ||||||
| Flavopiridol | Dysoxylum binectariferum | 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 |
Up-regulation | Cleavage | CASP1 | Molecule Info |
Pathway MAP
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| Up-regulation | Cleavage | CASP3 | Molecule Info |
Pathway MAP
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| Up-regulation | Cleavage | CASP8 | Molecule Info |
Pathway MAP
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| Down-regulation | Expression | p105 | Molecule Info |
Pathway MAP
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| Biological
Regulation |
Down-regulation | Chromosome | ||||
| In-vitro Model | A-549 | CVCL_0023 | Lung adenocarcinoma | Homo sapiens | ||
| HCT 116 | CVCL_0291 | Colon carcinoma | Homo sapiens | |||
| HCT 15 | CVCL_0292 | Colon adenocarcinoma | Homo sapiens | |||
| Experimental
Result(s) |
The cytotoxic synergy by the combination treatment involved the activation of caspase-1, caspase-3, and caspase-8 and generated huge chromosomal degradation. TNF-alpha treatment resulted in nuclear factor (NF)-kappa B activation, while flavopiridol inhibited the NF-kappa B-dependent gene transcription. | |||||
| Nimbolide | Azadirachta indica | Click to Show/Hide the Molecular Data of This NP | ||||
| Augmenting Drug Sensitivity | 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 | BID | Molecule Info |
Pathway MAP
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| Up-regulation | Cleavage | CASP3 | Molecule Info |
Pathway MAP
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| Up-regulation | Phosphorylation | JNK1 | Molecule Info |
Pathway MAP
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| Up-regulation | Expression | TRAIL-R2 | Molecule Info |
Pathway MAP
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| In-vitro Model | HT-29 | CVCL_0320 | Colon adenocarcinoma | Homo sapiens | ||
| Experimental
Result(s) |
Combination of nimbolide and TNF-alpha-Increases human colon adenocarcinoma cell death through JNK-mediated DR5 up- regulation. | |||||
| Triptolide | Tripterygium hypoglaucum | 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 | [4] | |||||
| Detail(s) |
Combination Info
click to show the detail info of this combination
|
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| Molecule(s)
Regulation |
Up-regulation | Expression | CASP3 | Molecule Info |
Pathway MAP
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| Up-regulation | Cleavage | COL11A2 | Molecule Info |
Pathway MAP
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| Down-regulation | Expression | p105 | Molecule Info |
Pathway MAP
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| In-vitro Model | MDA-MB-231 | CVCL_0062 | Breast adenocarcinoma | Homo sapiens | ||
| MCF-7 | CVCL_0031 | Invasive breast carcinoma | Homo sapiens | |||
| Experimental
Result(s) |
Triptolide sensitized human breast cancer cells to TNF Alpha induced apoptosis. | |||||
| Wogonin | Scutellaria amoena | Click to Show/Hide the Molecular Data of This NP | ||||
| Augmenting Drug Sensitivity | Click to Show/Hide | |||||
| Representative Experiment Reporting the Effect of This Combination | [5] | |||||
| Detail(s) |
Combination Info
click to show the detail info of this combination
|
|||||
| Molecule(s)
Regulation |
Down-regulation | Activity | p105 | Molecule Info |
Pathway MAP
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| Biological
Regulation |
Neutralization | TNFAlpha-induced free radical O2- | ||||
| In-vitro Model | ARAC-8C | CVCL_GZ09 | T acute lymphoblastic leukemia | Homo sapiens | ||
| Experimental
Result(s) |
Wogonin attenuates NF-kappaB activity by shifting TNFalpha-induced free radical .O(2)(-) to a more reduced nonradical product, H(2)O(2), and thereby sensitizes TNFalpha-resistant leukemia cells to TNFalpha-induced apoptosis. | |||||
| Target and Pathway | ||||
|---|---|---|---|---|
| Target(s) | Retinoic acid receptor RXR-alpha (RXRA) | Molecule Info | [6] | |
| Retinoic acid receptor RXR-beta (RXRB) | Molecule Info | [6] | ||
| Retinoic acid receptor RXR-gamma (RXRG) | Molecule Info | [6] | ||
| KEGG Pathway | PPAR signaling pathway | Click to Show/Hide | ||
| 2 | PI3K-Akt signaling pathway | |||
| 3 | Thyroid hormone signaling pathway | |||
| 4 | Adipocytokine signaling pathway | |||
| 5 | Non-alcoholic fatty liver disease (NAFLD) | |||
| 6 | Bile secretion | |||
| 7 | Hepatitis C | |||
| 8 | Pathways in cancer | |||
| 9 | Transcriptional misregulation in cancer | |||
| 10 | Thyroid cancer | |||
| 11 | Small cell lung cancer | |||
| 12 | Non-small cell lung cancer | |||
| Panther Pathway | Vitamin D metabolism and pathway | Click to Show/Hide | ||
| Pathway Interaction Database | Regulation of Androgen receptor activity | Click to Show/Hide | ||
| 2 | RXR and RAR heterodimerization with other nuclear receptor | |||
| 3 | Retinoic acid receptors-mediated signaling | |||
| 4 | a6b1 and a6b4 Integrin signaling | |||
| Reactome | RORA activates gene expression | Click to Show/Hide | ||
| 2 | BMAL1:CLOCK,NPAS2 activates circadian gene expression | |||
| 3 | Recycling of bile acids and salts | |||
| 4 | PPARA activates gene expression | |||
| 5 | Import of palmitoyl-CoA into the mitochondrial matrix | |||
| 6 | YAP1- and WWTR1 (TAZ)-stimulated gene expression | |||
| 7 | Regulation of pyruvate dehydrogenase (PDH) complex | |||
| 8 | Endogenous sterols | |||
| 9 | Transcriptional activation of mitochondrial biogenesis | |||
| 10 | Activation of gene expression by SREBF (SREBP) | |||
| 11 | Transcriptional regulation of white adipocyte differentiation | |||
| 12 | Nuclear Receptor transcription pathway | |||
| 13 | Regulation of lipid metabolism by Peroxisome proliferator-activated receptor alpha (PPARalpha) | |||
| 14 | Circadian Clock | |||
| WikiPathways | Vitamin A and Carotenoid Metabolism | Click to Show/Hide | ||
| 2 | NRF2 pathway | |||
| 3 | Nuclear Receptors Meta-Pathway | |||
| 4 | Farnesoid X Receptor Pathway | |||
| 5 | PPAR Alpha Pathway | |||
| 6 | Vitamin D Receptor Pathway | |||
| 7 | Pregnane X Receptor pathway | |||
| 8 | Constitutive Androstane Receptor Pathway | |||
| 9 | Liver X Receptor Pathway | |||
| 10 | Regulation of Lipid Metabolism by Peroxisome proliferator-activated receptor alpha (PPARalpha) | |||
| 11 | Transcriptional Regulation of White Adipocyte Differentiation | |||
| 12 | YAP1- and WWTR1 (TAZ)-stimulated gene expression | |||
| 13 | Activation of Gene Expression by SREBP (SREBF) | |||
| 14 | Integrated Pancreatic Cancer Pathway | |||
| 15 | Adipogenesis | |||
| 16 | Circadian Clock | |||
| 17 | Nuclear Receptors | |||
| 18 | Vitamin D Metabolism | |||
