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| Targets |
The primary targets of TPOP146 are the CBP/P300 bromodomain and the p53-MDM2 interaction. As a CBP/P300 bromodomain inhibitor, TPOP146 binds to the bromodomain of these transcriptional coactivators, inhibiting their interaction with acetylated lysine residues on histones and other proteins. As a p53-MDM2 interaction inhibitor, TPOP146 blocks the binding of MDM2 to p53, stabilizing and activating p53. This dual mechanism of action makes TPOP146 a valuable tool for studying epigenetic regulation and the p53 pathway.
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| ln Vitro |
Exposure to 1 μM TPOP146 led to a significantly reduced recovery half-life, which was similar to constructs with the bromodomain-inactivating mutation N1168F. This suggests that TPOP146 interacts with acetyl lysine-mediated research on the function of CBP bromodomain in a competitive cellular environment and targets the CBP bromodomain in the nucleus[1].
In vitro, TPOP146 demonstrates potent and selective inhibition of the CBP/P300 bromodomain. It shows 134 nM affinity for CBP with excellent selectivity over other bromodomains. The compound's activity is assessed in binding assays using recombinant bromodomain proteins and labeled acetylated peptide probes. As a p53-MDM2 interaction inhibitor, TPOP146 blocks the binding of MDM2 to p53, leading to p53 stabilization and activation. However, detailed IC50 values are not extensively reported. |
| ln Vivo |
In vivo data for TPOP146 are not extensively reported in the available literature. As a dual inhibitor of CBP/P300 bromodomain and p53-MDM2 interaction, the compound has potential for in vivo applications in cancer models. However, specific in vivo efficacy data, including animal models, dosing regimens, and pharmacokinetic-pharmacodynamic relationships, are not detailed in the available sources. The compound is classified as a research-use-only chemical.
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| Enzyme Assay |
In vitro receptor binding assays for TPOP146 typically involve measuring its affinity for the CBP/P300 bromodomain. Recombinant bromodomain proteins are incubated with a labeled acetylated peptide probe in the presence of varying concentrations of TPOP146. The displacement of the probe is measured, and the affinity (e.g., 134 nM for CBP) is calculated. Selectivity over other bromodomains is assessed by profiling against a panel of bromodomain proteins.
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| Cell Assay |
Cellular assays for TPOP146 are performed in cancer cell lines to assess its effects on CBP/P300 function and the p53 pathway. Cells are treated with TPOP146, and the acetylation status of histones and other proteins is measured. The expression of p53 target genes is assessed by RT-PCR. The compound's effects on cell proliferation, apoptosis, and cell cycle progression are also assessed.
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| Animal Protocol |
In vivo animal studies with TPOP146 are not extensively documented in the available literature. Based on its dual mechanism of action, potential in vivo models could include xenograft models for cancer. In such studies, TPOP146 would be administered systemically, and tumor growth would be monitored. However, specific protocols are not detailed in the available sources.
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| ADME/Pharmacokinetics |
TPOP146 has a molecular weight of 481.58 and a molecular formula of C27H35N3O5. It is soluble in DMSO at ≥90 mg/mL. The compound is stable as a powder when stored at -20°C for up to 3 years and in solution at -80°C for up to 6 months. However, detailed pharmacokinetic parameters are not available in the literature for this research compound.
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| Toxicity/Toxicokinetics |
Comprehensive toxicology data for TPOP146 are not extensively reported. The compound is classified as a research-use-only chemical and is not intended for human consumption. Specific toxicological data, including acute toxicity, genotoxicity, and target organ effects, are not reported in the available literature.
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| References | |
| Additional Infomation |
TPOP146 is a research-grade compound not approved for clinical use. Its primary applications are in epigenetics and cancer research. The compound is used to study the role of CBP/P300 bromodomain in transcriptional regulation and the function of the p53 pathway in tumor suppression. Its dual mechanism of action makes it a valuable tool for investigating the interplay between epigenetic regulation and the p53 tumor suppressor pathway.
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| Molecular Formula |
C27H35N3O5
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| Molecular Weight |
481.593
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| Exact Mass |
481.257
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| CAS # |
2018300-62-2
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| PubChem CID |
122172830
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| Appearance |
White to off-white solid powder
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| Density |
1.2±0.1 g/cm3
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| Boiling Point |
641.8±55.0 °C at 760 mmHg
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| Flash Point |
341.9±31.5 °C
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| Vapour Pressure |
0.0±1.9 mmHg at 25°C
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| Index of Refraction |
1.607
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| LogP |
2.01
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
35
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| Complexity |
709
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| Defined Atom Stereocenter Count |
1
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| SMILES |
CCC(=O)N1CCOC2=C(C1)C=C(C=C2C(=O)N[C@H]3CCCN(C3)C)C4=CC(=CC(=C4)OC)OC
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| InChi Key |
CUJLWYCUPPPASA-NRFANRHFSA-N
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| InChi Code |
InChI=1S/C27H35N3O5/c1-5-25(31)30-9-10-35-26-20(16-30)11-18(19-12-22(33-3)15-23(13-19)34-4)14-24(26)27(32)28-21-7-6-8-29(2)17-21/h11-15,21H,5-10,16-17H2,1-4H3,(H,28,32)/t21-/m0/s1
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| Chemical Name |
(S)-7-(3,5-dimethoxyphenyl)-N-(1-methylpiperidin-3-yl)-4-propionyl-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine-9-carboxamide
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| Synonyms |
TPOP-146 TPOP 146TPOP146
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : ~21.43 mg/mL (~44.50 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: 2.14 mg/mL (4.44 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution; with sonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 21.4 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: 2.14 mg/mL (4.44 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 21.4 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: 2.14 mg/mL (4.44 mM) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.0765 mL | 10.3823 mL | 20.7646 mL | |
| 5 mM | 0.4153 mL | 2.0765 mL | 4.1529 mL | |
| 10 mM | 0.2076 mL | 1.0382 mL | 2.0765 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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