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| Other Sizes |
| Targets |
TASIN-30 selectively targets Emopamil binding protein (EBP), which is an integral membrane protein that catalyzes the isomerization of delta8-delta7 sterols in the cholesterol biosynthesis pathway. EBP is also known as the delta8-delta7 sterol isomerase. The compound inhibits EBP with high potency and selectivity, with a competitive EC50 value of 0.097 microM (97 nM). TASIN-30 shows significant selectivity for EBP over other enzymes in the sterol biosynthesis pathway, including DHCR7 (50 microM EC50, ~515-fold selectivity). This selectivity is important for minimizing off-target effects on related metabolic pathways.
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| ln Vitro |
TASIN-30 potently inhibits EBP with a competitive EC50 value of 0.097 microM (97 nM). It shows high selectivity for EBP over DHCR7, with a competitive EC50 value for DHCR7 of 50 microM, representing approximately 515-fold selectivity. By inhibiting EBP, TASIN-30 disrupts cholesterol biosynthesis, leading to the accumulation of desmosterol and other sterol intermediates. In cancer cells that are dependent on cholesterol metabolism for growth and survival (e.g., certain colon cancer cells), this disruption induces cell cycle arrest and apoptosis. The compound has been shown to selectively kill colon cancer cells with KRAS mutations, suggesting a potential synthetic lethal interaction.
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| ln Vivo |
Specific in vivo activity data for TASIN-30 is not detailed in the search results. As a small molecule inhibitor of EBP with potent in vitro activity and high selectivity, TASIN-30 is expected to show anti-tumor activity in xenograft models of colon cancer. By inhibiting cholesterol biosynthesis in tumor cells, it may reduce tumor growth and induce cell death. The high selectivity for EBP over other sterol biosynthetic enzymes may translate into a favorable therapeutic window with reduced toxicity compared to broad-spectrum cholesterol synthesis inhibitors.
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| Enzyme Assay |
The inhibitory activity of TASIN-30 against EBP can be assessed using a cell-free sterol isomerase activity assay. Procedure: Microsomes containing recombinant human EBP are prepared from EBP-overexpressing HEK-293 cells. Microsomal protein (50 microg) is incubated with varying concentrations of TASIN-30 (e.g., 0.001, 0.01, 0.1, 1, 10, 100 microM) in assay buffer (50 mM potassium phosphate, pH 7.4, 5 mM DTT) for 10 minutes at room temperature. The substrate, 14C-radiolabeled delta8-cholestenol (10 microM), is added and the reaction is incubated at 37degC for 30 minutes. Lipids are extracted with hexane/isopropanol, separated by thin-layer chromatography (TLC), and quantified by autoradiography or phosphorimaging. The conversion of delta8-cholestenol to delta7-cholestenol is measured, and the EC50 value is calculated from the dose-response curve. Alternatively, a fluorescence-based assay can be used with a synthetic substrate if available.
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| Cell Assay |
The growth inhibitory effect of TASIN-30 can be assessed in colon cancer cell lines. Procedure: Human colon cancer cell lines (e.g., HCT116, DLD-1, SW480, with or without KRAS mutations) are seeded in 96-well plates at 5,000-10,000 cells per well in RPMI-1640 or DMEM with 10% FBS. After 24 hours, cells are treated with serial dilutions of TASIN-30 (e.g., 0.01, 0.1, 0.5, 1, 2, 5, 10, 25, 50 microM) for 72 hours. Cell viability is measured using the CellTiter-Glo luminescent assay or MTS assay. IC50 values are calculated from dose-response curves. To assess the mechanism of cell death, cells are treated with TASIN-30 for 48 hours, then stained with Annexin V-FITC and propidium iodide for flow cytometry analysis. The effect on cholesterol metabolism is confirmed by measuring desmosterol (the substrate that accumulates when EBP is inhibited) and cholesterol levels in cells by LC-MS/MS.
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| Animal Protocol |
The in vivo efficacy of TASIN-30 can be evaluated in a mouse xenograft model of colon cancer. Procedure: 6-8 week old female athymic nude mice are inoculated subcutaneously with 5×10^6 HCT116 or DLD-1 (KRAS-mutant) colon cancer cells in 50% Matrigel. When tumors reach an average size of 100-150 mm3, mice are randomized into treatment groups (n=8-10 per group). TASIN-30 is administered orally by gavage at doses of 10, 30, 100 mg/kg once daily for 21-28 days. Tumor volumes are measured every 3 days with digital calipers. Body weights are recorded to monitor general toxicity. At study endpoint, tumors are harvested for analysis of sterol levels (desmosterol accumulation by LC-MS/MS), proliferation (Ki-67 immunohistochemistry), and apoptosis (TUNEL assay). Tumor growth inhibition (TGI) is calculated as the percentage reduction in tumor volume compared to the vehicle control group.
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| ADME/Pharmacokinetics |
Specific pharmacokinetic data for TASIN-30 is not provided. As a small molecule with a molecular weight of 354.51 Da, it is within the range for good oral absorption. The compound is typically administered orally in in vivo studies. The presence of a sulfonyl group (S in the molecular formula) and an amide functionality may influence its metabolic stability. The compound's high selectivity for EBP suggests that it achieves sufficient systemic exposure to inhibit the target. Pharmacokinetic studies would be required to determine oral bioavailability, half-life, and tissue distribution in preclinical species.
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| Toxicity/Toxicokinetics |
Specific toxicity data for TASIN-30 is not available. As an inhibitor of the cholesterol biosynthesis pathway, potential on-target toxicities may include the class-related effects of statins and other cholesterol synthesis inhibitors, such as myopathy, hepatotoxicity, and effects on steroid hormone synthesis. However, the high selectivity of TASIN-30 for EBP over other sterol biosynthesis enzymes may reduce certain off-target toxicities. The compound has shown selectivity for cancer cells over normal cells in vitro, suggesting a potential therapeutic window. Comprehensive toxicological evaluation would be required for clinical development.
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| References | |
| Additional Infomation |
TASIN-30 is a selective inhibitor of Emopamil binding protein (EBP), which is a sterol isomerase that converts delta8-cholestenol to delta7-cholestenol in the post-squalene cholesterol biosynthesis pathway. EBP is also known as the delta8-delta7 sterol isomerase. The gene encoding EBP (EBP) is located on the X chromosome and mutations in EBP cause Conradi-Hünermann-Happle syndrome (X-linked dominant chondrodysplasia punctata), a rare genetic disorder affecting bone and skin development. TASIN-30 was developed as part of a strategy to target cholesterol-dependent cancers, particularly those with KRAS mutations that render them sensitive to perturbations in cholesterol metabolism. The compound has a competitive EC50 value of 0.097 microM for EBP and shows >500-fold selectivity over DHCR7 (50 microM). It is for research use only and is not an approved drug. The compound is typically stored at -20degC as a white to off-white solid powder. TASIN-30 may also be used in combination with other metabolic inhibitors to enhance anti-cancer efficacy. Purity is reported to be 99.96%.
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| Molecular Formula |
C18H30N2O3S
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| Molecular Weight |
354.51
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| Exact Mass |
354.198
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| CAS # |
1678515-93-9
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| PubChem CID |
118308351
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| Appearance |
White to off-white solid powder
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
24
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| Complexity |
471
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CC1=CC(=C(C(=C1)C)S(=O)(=O)N2CCC(CC2)NCCC(C)O)C
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| InChi Key |
KWHTXYFUJIBRNB-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C18H30N2O3S/c1-13-11-14(2)18(15(3)12-13)24(22,23)20-9-6-17(7-10-20)19-8-5-16(4)21/h11-12,16-17,19,21H,5-10H2,1-4H3
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| Chemical Name |
4-[[1-(2,4,6-trimethylphenyl)sulfonylpiperidin-4-yl]amino]butan-2-ol
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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 (~282.08 mM; with ultrasonication)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (7.05 mM) (saturation unknown) 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。
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 (7.05 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 the 25.0 mg/mL clear DMSO stock solution to 900 μL corn oil and mix well. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.8208 mL | 14.1040 mL | 28.2079 mL | |
| 5 mM | 0.5642 mL | 2.8208 mL | 5.6416 mL | |
| 10 mM | 0.2821 mL | 1.4104 mL | 2.8208 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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