| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
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| 5mg | |||
| Other Sizes |
| Targets |
IC50: 1.646 ± 0.024 μM (TRAP1)[1]
TRAP1 (Tumor Necrosis Factor Receptor-Associated Protein 1). SMTIN-T140 is a potent inhibitor of TRAP1, with an IC50 of 1.646 microM. TRAP1 is a mitochondrial chaperone that protects cancer cells from oxidative stress. By inhibiting TRAP1, SMTIN-T140 disrupts mitochondrial function, leading to increased ROS, activation of AMPK, and cell death. Some sources also indicate it may block the CXCR4 chemokine receptor, inhibiting cancer cell migration. |
|---|---|
| ln Vitro |
In vitro, SMTIN-T140 has been shown to cause mitochondrial dysfunction and increase the production of mitochondrial reactive oxygen species (ROS) in cancer cells. This activity leads to the activation of the cellular energy sensor AMPK. The compound effectively inhibits the viability and proliferation of cancer cells in culture, including prostate cancer cells. Its IC50 for TRAP1 inhibition is 1.646 microM, indicating its potency against this target.
|
| ln Vivo |
In vivo, SMTIN-T140 potently suppresses tumor growth without any noticeable toxicity in a mouse model xenografted with PC3 human prostate cancer cells. These results suggest that the compound is well-tolerated at therapeutic doses and has significant anticancer efficacy. This favorable safety/efficacy profile makes it a promising candidate for further development.
|
| Enzyme Assay |
Standard cell‑free binding assays for SMTIN-T140 can be performed to measure its interaction with TRAP1. Recombinant human TRAP1 protein is immobilized on a sensor chip. A buffer containing a range of SMTIN-T140 concentrations is passed over the chip. The IC50 value for binding is determined. Alternatively, a fluorescence polarization (FP) assay can be developed using a fluorescently labeled tracer molecule known to bind to the active site of TRAP1. SMTIN-T140 competes with the tracer, leading to a decrease in polarization. The IC50 is calculated from the competition curve. For the CXCR4 target, a radioligand binding assay using ¹2⁵I‑CXCL12 and CXCR4‑expressing cell membranes can be performed, though the IC50 is not listed.
|
| Cell Assay |
For cellular assays, PC3 human prostate cancer cells are seeded in 96‑well plates (5,000 cells/well) in DMEM/10% FBS. After 24 hours, cells are treated with varying concentrations of SMTIN-T140 (0.1-100 uM) for 48 hours. Cell viability is measured using the MTT or CellTiter-Glo assay. To measure mitochondrial ROS, cells are treated with SMTIN-T140 for 4-6 hours, then loaded with the mitochondrial superoxide indicator MitoSOX Red (5 uM) for 10 minutes. Fluorescence is measured (ex 510 nm, em 580 nm). For AMPK activation, cells are treated with SMTIN-T140 for 6-24 hours, lysed, and analyzed by Western blot using antibodies against phospho-AMPK (Thr172) and total AMPK. An increase in the p-AMPK/AMPK ratio indicates pathway activation. Apoptosis is assessed by flow cytometry using an Annexin V-FITC/Propidium Iodide (PI) staining kit.
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| Animal Protocol |
In vivo studies are performed in male athymic nude mice (6-8 weeks old). Mice are injected subcutaneously in the flank with 5×10⁶ PC3 human prostate cancer cells in Matrigel. When tumors reach a volume of approximately 150-200 mm3, the mice are randomized into treatment groups (n=6-8). SMTIN-T140 is formulated in an appropriate vehicle (e.g., 10% DMSO in saline) and administered by intraperitoneal injection at a dose of 10-20 mg/kg once daily for 2-3 weeks. Tumor volume is measured with calipers every 2-3 days, and body weight is monitored for signs of toxicity. At the end of the study, mice are euthanized, and tumors are excised and weighed. Tumor sections are prepared for histological analysis, including H&E staining to assess necrosis and TUNEL staining to detect apoptotic cells. Tumor lysates are also analyzed by Western blot to confirm the inhibition of TRAP1 and the activation of AMPK in vivo.
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| ADME/Pharmacokinetics |
As a synthetic peptide, SMTIN-T140 is expected to have a short half-life in circulation due to proteolysis. It is formulated in saline for intraperitoneal injection in research settings. It is not orally bioavailable. The compound is soluble in DMSO. Its pharmacokinetic properties are not well-documented in the provided sources, and it is considered a research tool primarily for in vitro and ex vivo use.
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| Toxicity/Toxicokinetics |
In a mouse model xenografted with PC3 prostate cancer cells, SMTIN-T140 potently suppressed tumor growth without any noticeable in vivo toxicity. This suggests a favorable safety profile at therapeutic doses. No detailed toxicological data on major organ systems (liver, kidney, heart) are provided in the summary.
|
| References |
| Molecular Formula |
C36H34BRCLFN5OP
|
|---|---|
| Molecular Weight |
718.017230510712
|
| Exact Mass |
716.135
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| CAS # |
2851532-40-4
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| PubChem CID |
163409182
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| Appearance |
Off-white to light yellow solid powder
|
| LogP |
8.3
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| Hydrogen Bond Donor Count |
1
|
| Hydrogen Bond Acceptor Count |
5
|
| Rotatable Bond Count |
12
|
| Heavy Atom Count |
46
|
| Complexity |
921
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
C1=CC=C(C=C1)[P+](CCCCCCN2C3=C(N=C(N=C3Cl)N)N(C2=O)CC4=C(C=C(C=C4)Br)F)(C5=CC=CC=C5)C6=CC=CC=C6
|
| InChi Key |
WMHQIAATFFUMMC-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C36H34BrClFN5OP/c37-27-21-20-26(31(39)24-27)25-44-34-32(33(38)41-35(40)42-34)43(36(44)45)22-12-1-2-13-23-46(28-14-6-3-7-15-28,29-16-8-4-9-17-29)30-18-10-5-11-19-30/h3-11,14-21,24H,1-2,12-13,22-23,25H2,(H2,40,41,42)/q+1
|
| Chemical Name |
6-[2-amino-9-[(4-bromo-2-fluorophenyl)methyl]-6-chloro-8-oxopurin-7-yl]hexyl-triphenylphosphanium
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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: ~100 mg/mL (~139.3 mM; with ultrasonication)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: 2.5 mg/mL (3.48 mM) in 10% DMSO + 40% PEG300 + 5% Tween-80 + 45% 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 DMSO stock solution (25.0 mg/mL) to 400 μL of PEG300 and mix well; then add 50 μL of Tween-80 and mix well; finally add 450 μL of physiological saline and 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: 2.5 mg/mL (3.48 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 DMSO stock solution (25.0 mg/mL) to 900 μL of 20% SBE-β-CD saline and mix well. 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.3927 mL | 6.9636 mL | 13.9272 mL | |
| 5 mM | 0.2785 mL | 1.3927 mL | 2.7854 mL | |
| 10 mM | 0.1393 mL | 0.6964 mL | 1.3927 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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