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| 1mg |
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| Other Sizes |
Purity: ≥98%
| Targets |
TCH-165 targets the proteasome, specifically the 20S proteasome complex. It modulates the dynamic equilibrium between the 20S and 26S proteasome complexes, favoring 20S-mediated protein degradation. By increasing 20S levels, TCH-165 enhances the degradation of intrinsically disordered proteins (IDPs). The compound regulates proteasome assembly and promotes proteolysis.
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| ln Vitro |
TCH-165 (0.01-10 μM; 72 hours) inhibits RPMI8226 and U87MG cell growth, with IC50 values of 1.6 μM and 2.4 μM, in that order [1]. TCH-165 (0–10 μM; 24 hours; HEK293T cells) Boosts ODC TCH-165, in a concentration-dependent way, boosts proteolysis [1]. TCH-165 improves the affinity of chymotrypsin-like (CT-L), trypsin-like (Tryp-L), and caspase-like (Casp). It also improves α-syn, tau, and 20S-mediated IDPs. However, it does not improve the affinity of structural proteins like GAPDH [1]. -L) activity, the corresponding EC50 values are 4.2 μM, 3.2 μM, and 4.7 μM [1]. Cells treated with TCH-165 displayed an increase in 20S proteasome and a decrease in reconstituted 26S proteasome. TCH-165 promotes 20S-mediated protein degradation by controlling the dynamic equilibrium between 26S and 20S proteasome complexes [1]. [1]
In vitro, TCH-165 is a small molecule modulator of proteasome assembly that increases 20S levels and promotes 20S-mediated protein degradation. It selectively activates the chymotrypsin-like (EC50 = 4.2), trypsin-like, and caspase-like activities of the 20S proteasome. The compound's activity is assessed by measuring proteasome activity and 20S proteasome levels in cell-free systems. |
| ln Vivo |
In vivo, TCH-165 has been studied in models of diseases involving protein aggregation and proteasome dysfunction. By increasing 20S proteasome levels, the compound promotes the degradation of intrinsically disordered proteins and may have therapeutic potential in neurodegenerative diseases and cancer.
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| Enzyme Assay |
In vitro enzyme assays for TCH-165 measure its effects on proteasome activity. The 20S proteasome is incubated with fluorogenic substrates (e.g., Suc-LLVY-AMC for chymotrypsin-like activity) and varying concentrations of the compound. Proteasome activity is measured by fluorescence, and EC50 values for activation of chymotrypsin-like, trypsin-like, and caspase-like activities are determined.
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| Cell Assay |
Cell Viability Assay[1]
Cell Types: RPMI8226 and U87MG cells Tested Concentrations: 0.01-10 μM Incubation Duration: 72 hrs (hours) Experimental Results: Inhibits the growth of RPMI8226 and U87MG cells with IC50 of 1.6 μM and 2.4 μM respectively. Western Blot Analysis[1] Cell Types: HEK293T Cell Tested Concentrations: 0 μM, 3 μM, 10 μM Incubation Duration: 24 hrs (hours) Experimental Results: Proteolytic degradation is enhanced in a concentration-dependent manner. In vitro cell-based assays for TCH-165 assess its effects on proteasome assembly and protein degradation in cultured cells. Cells are treated with serial dilutions of the compound, and 20S proteasome levels are measured by Western blotting or activity assays. Degradation of intrinsically disordered proteins is assessed by measuring protein levels. Cell viability and proliferation are measured in parallel. |
| Animal Protocol |
In vivo animal models for TCH-165 include models of neurodegenerative diseases and cancer. The compound is administered via appropriate routes, and its effects on proteasome activity, protein aggregation, and disease progression are evaluated. Pharmacodynamic studies measure 20S proteasome levels and proteasome activity in target tissues.
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| ADME/Pharmacokinetics |
TCH-165 has a molecular formula of C39H37N3O3 and a molecular weight of 595.73 g/mol. It is stored at -20°C and has a purity of ≥98%. The compound is also known as TCH165 and is soluble in DMSO. It is intended for laboratory research use only and is not for human use.
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| Toxicity/Toxicokinetics |
The toxicity profile of TCH-165 is characterized in preclinical safety studies. As a modulator of proteasome assembly, the compound may affect protein homeostasis and cellular function. The compound is for research use only and is not approved for clinical use. Appropriate safety precautions should be taken during handling.
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| References | |
| Additional Infomation |
TCH-165 is a small molecule modulator of proteasome assembly that increases 20S levels and promotes 20S-mediated protein degradation. It selectively activates the chymotrypsin-like, trypsin-like, and caspase-like activities of the 20S proteasome. TCH-165 regulates the dynamic equilibrium between the 20S and 26S proteasome complexes and enhances proteolysis of intrinsically disordered proteins. It is intended for laboratory research use only.
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| Molecular Formula |
C39H37N3O3
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|---|---|
| Molecular Weight |
595.7294
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| Exact Mass |
595.28
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| Elemental Analysis |
C, 78.63; H, 6.26; N, 7.05; O, 8.06
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| CAS # |
1446350-60-2
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| PubChem CID |
71762768
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| Appearance |
Light yellow to yellow solid powder
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| LogP |
7.5
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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 |
12
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| Heavy Atom Count |
45
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| Complexity |
937
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| Defined Atom Stereocenter Count |
2
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| SMILES |
CCOC(=O)[C@]1([C@H](N(C(=N1)C2=CC=C(C=C2)OC)CC3=CC=CC=C3)C4=CC=C(C=C4)NCC5=CC=CC=C5)C6=CC=CC=C6
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| InChi Key |
XXDLWRCUPASJGY-VQIIKMDRSA-N
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| InChi Code |
InChI=1S/C39H37N3O3/c1-3-45-38(43)39(33-17-11-6-12-18-33)36(31-19-23-34(24-20-31)40-27-29-13-7-4-8-14-29)42(28-30-15-9-5-10-16-30)37(41-39)32-21-25-35(44-2)26-22-32/h4-26,36,40H,3,27-28H2,1-2H3/t36-,39-/m0/s1
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| Chemical Name |
Ethyl (4S,5S)-1-benzyl-5-(4-(benzylamino)phenyl)-2-(4-methoxyphenyl)-4-phenyl-4,5-dihydro-1H-imidazole-4-carboxylate
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| Synonyms |
TCH-165 TCH 165 TCH165
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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 : ~250 mg/mL (~419.65 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 6.25 mg/mL (10.49 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 62.5 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: ≥ 6.25 mg/mL (10.49 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 62.5 mg/mL clear DMSO stock solution to 900 μL corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.6786 mL | 8.3931 mL | 16.7861 mL | |
| 5 mM | 0.3357 mL | 1.6786 mL | 3.3572 mL | |
| 10 mM | 0.1679 mL | 0.8393 mL | 1.6786 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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