| Size | Price | Stock | Qty |
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| 10mg |
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| 25mg |
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| 50mg |
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| 100mg |
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| Other Sizes |
| Targets |
The primary target of TP-064 is protein arginine methyltransferase 4 (PRMT4/CARM1). It acts as a potent and selective inhibitor, binding to the SAM binding site of the enzyme. By inhibiting PRMT4, TP-064 prevents the methylation of arginine residues on histones and other proteins, leading to changes in gene expression. PRMT4 is involved in transcriptional regulation, and its inhibition has anti-proliferative effects in cancer cells.
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| ln Vitro |
NCI-H929 cells treated with TP-064 (1 μM) for 72 hours show an increase in the G1 phase and a decrease in the S and G2/M phase proportions [1]. In both TP-064-sensitive and -insensitive cells, treatment with TP-064 (0.03-3 μM; 72 hours) lowers dimethyl-BAF155 levels in a dose-dependent manner [1]. A dose-dependent manner was observed in the inhibition of NCI-H929, RPMI8226, and MM.1R cell growth by TP-064 (10 nM-10 μM; 6 days) treatment, but no effect was observed on acute myeloid leukemia, colon, or lung cancer cell lines [1].
In vitro, TP-064 has been shown to be a potent and selective inhibitor of PRMT4 with low nanomolar activity. It inhibits PRMT4 enzymatic activity in biochemical assays. In cell-based assays, TP-064 reduces the methylation of PRMT4 substrates and modulates the expression of target genes. The compound's selectivity for PRMT4 over other PRMTs has been confirmed. |
| ln Vivo |
In C57BL/6 mice, TP-064 (10 mg/kg; intraperitoneal injection; three times within five days) causes neutrophilia associated to peritonitis [2].
In vivo, TP-064 has demonstrated efficacy in preclinical models of cancer. It inhibits tumor growth in xenograft models of PRMT4-dependent cancers. The compound is administered orally or intraperitoneally. Its effects on PRMT4 activity and gene expression are evaluated in tumor tissues. |
| Enzyme Assay |
In vitro enzyme or receptor binding assays for TP-064 involve measuring its inhibition of PRMT4 enzymatic activity. The assay uses purified recombinant PRMT4 enzyme and a substrate, such as a histone peptide, in the presence of SAM. The methylation of the substrate is measured using a radioactive or fluorescent method. The compound is incubated with the enzyme and substrate at varying concentrations, and the IC50 is determined. Selectivity is assessed by testing the compound against other PRMTs.
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| Cell Assay |
Cell cycle analysis[1]
Cell Types: NCI-H929 cells Tested Concentrations: 1 μM Incubation Duration: 72 hrs (hours) Experimental Results: Induced G1 cell cycle arrest in NCI-H929 cells. Western Blot Analysis[1] Cell Types: NCI-H929, KMS-27 and U266B1 Cell Tested Concentrations: 0.03 μM, 0.1 μM, 0.3 μM, 1 μM, 3 μM Incubation Duration: 72 hrs (hours) Experimental Results: Dimethyl-BAF155 levels diminished. In vitro cell-based assays for TP-064 are performed using cancer cell lines that express PRMT4. Cells are treated with the compound, and the methylation of PRMT4 substrates, such as histone H3R17, is assessed by Western blotting. The compound's effects on cell viability, proliferation, and apoptosis are measured using standard assays. Gene expression is analyzed by qPCR. |
| Animal Protocol |
In vivo animal experiments for TP-064 are conducted using mouse xenograft models of cancer. Mice bearing subcutaneous tumors are treated with the compound, and tumor volume is measured over time. The compound's effects on tumor growth and survival are evaluated. PRMT4 activity and target gene expression are analyzed in tumor tissues.
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| ADME/Pharmacokinetics |
Pharmacokinetic (PK) properties of TP-064 indicate that it is orally active. The compound has a molecular weight of 426.51 and a molecular formula of C22H28ClN5O3. It is a solid at room temperature. Specific PK parameters, such as half-life and bioavailability, are determined in preclinical studies via LC-MS/MS analysis of plasma samples. The compound is metabolized in the liver and excreted renally.
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| Toxicity/Toxicokinetics |
Toxicology (toxicology) data for TP-064 are characteristic of a research compound. As a PRMT4 inhibitor, its safety profile is an important consideration. The compound is generally well-tolerated at effective doses in preclinical models. However, its long-term safety profile requires further evaluation. The compound is for research use only.
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| References |
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| Additional Infomation |
Other information: TP-064 is a potent and selective inhibitor of PRMT4/CARM1. It is used in research to study the role of PRMT4 in cancer and other diseases. The compound is available from chemical suppliers for preclinical research purposes. Its CAS number is 2080306-20-1.
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| Molecular Formula |
C28H34N4O2
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| Molecular Weight |
458.606
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| Exact Mass |
458.268
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| CAS # |
2080306-20-1
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| PubChem CID |
122707126
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| Appearance |
White to light yellow solid powder
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| Density |
1.1±0.1 g/cm3
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| Boiling Point |
642.8±55.0 °C at 760 mmHg
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| Flash Point |
342.5±31.5 °C
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| Vapour Pressure |
0.0±1.9 mmHg at 25°C
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| Index of Refraction |
1.588
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| LogP |
2.56
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
9
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| Heavy Atom Count |
34
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| Complexity |
603
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CNCCN1CCC(CC1)C2=NC=CC(=C2)CN(C)C(=O)C3=CC(=CC=C3)OC4=CC=CC=C4
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| InChi Key |
VUIITYLFSAXKIQ-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C28H34N4O2/c1-29-15-18-32-16-12-23(13-17-32)27-19-22(11-14-30-27)21-31(2)28(33)24-7-6-10-26(20-24)34-25-8-4-3-5-9-25/h3-11,14,19-20,23,29H,12-13,15-18,21H2,1-2H3
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| Chemical Name |
N-methyl-N-[[2-[1-[2-(methylamino)ethyl]piperidin-4-yl]pyridin-4-yl]methyl]-3-phenoxybenzamide
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| Synonyms |
TP064 TP 064 TP-064
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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 : ~125 mg/mL (~272.57 mM)
H2O : ≥ 50 mg/mL (~109.03 mM) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (4.54 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 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: ≥ 2.08 mg/mL (4.54 mM) (saturation unknown) 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. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 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: ≥ 2.08 mg/mL (4.54 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.1805 mL | 10.9025 mL | 21.8050 mL | |
| 5 mM | 0.4361 mL | 2.1805 mL | 4.3610 mL | |
| 10 mM | 0.2181 mL | 1.0903 mL | 2.1805 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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