TASIN-1 |
| カタログ番号GC11469 |
TASIN-1 は、切断型 APC 遺伝子 (大腸腺腫症遺伝子) の選択的阻害剤であり、コレステロール生合成の阻害を通じて細胞毒性効果を発揮します。 TASIN-1 は、変異型 APC による CRC の予防と介入のための潜在的な治療戦略を表しています。
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 792927-06-1
Sample solution is provided at 25 µL, 10mM.
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TASIN-1 is a small molecule inhibitor of mutant adenomatous polyposis coli (APC) [1].
Adenomatous polyposis coli (APC) is a multifunctional tumor suppressor gene that is mutated in more than 80% of colon tumors. APC plays an important role in the negative regulation of canonical WNT signaling pathway through proteasomal degradation of b-catenin. APC is involved in cell cycle control, migration, differentiation, and apoptosis [1].
TASIN-1 is a selective inhibitor of mutant APC. In two authentic human CRC cell lines HCT116 (WT APC) and DLD1 (truncated APC1417), TASIN-1 exhibited potent and selective toxicity toward DLD1 cells with IC50 value of 70 nM but not toward HCT116 cells (IC50 >50 μM). TASIN-1 also reduced the endogenous cholesterol biosynthesis rate. TASIN-1 exerted its killing effects primarily by depleting cholesterol through inhibition of emopamil-binding protein (EBP) activity. However, knockdown of truncated APC (>90%) expression desensitized DLD1 cells to TASIN-1, suggesting that APC is required for TASIN-1's cytotoxicity [1].
In nude mice with established DLD1 and HT29 tumors, intraperitoneal injection of TASIN-1 twice daily for 18 days reduced the size of tumor xenografts and tumor growth rates. TASIN-1 resulted in the appearance of apoptotic cells with fragmented nuclei and induced an increase in cleaved caspase 3 and cleaved PARP1. However, TASIN-1 did not inhibit tumor growth in HCT116 (WT APC) xenografts. In a genetically engineered CRC mouse model, TASIN-1 significantly reduced tumor formation in the colons of CPC;Apc mice [1].
Reference:
1.Lu Zhang, Panayotis C. Theodoropoulos, Ugur Eskiocak, et al. Selective targeting of mutant adenomatous polyposis coli (APC) in colorectal cancer. Science Translational Medicine 19 Oct 2016: Vol. 8, Issue 361, pp. 361ra140.
| Cell experiment [1]: | |
|
Cell lines |
HCT116 (WT APC) and DLD1 (truncated APC1417) cell lines |
|
Preparation method |
This compound is soluble in DMSO. General tips for obtaining a higher concentration: Please warm the tube at 37℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months. |
|
Reacting condition |
0.0001-100 μM; 48 h |
|
Applications |
TASIN-1 exhibited potent and selective toxicity toward DLD1 cells with IC50 value of 70 nM. TASIN-1 inhibited soft agar growth only in DLD1 cells. When cultured in medium with 0.1% serum for 7 days, HCT116 cells showed similar sensitivity to TASIN-1 as DLD1 cells. |
| Animal experiment [1]: | |
|
Animal models |
genetically engineered colorectal cancer (CRC) mouse model |
|
Dosage form |
20 mg/kg twice per week for 90 days or 40 mg/kg per week for 100 days (dissolved in 0.2 ml of solvent containing 10% DMSO and 10% cremophor); intraperitoneal injection |
|
Application |
In genetically engineered colorectal cancer (CRC) mouse model, TASIN-1 had a long retention time in mouse large intestinal tissue. TASIN-1 significantly reduced tumor formation in the colons. TASIN-1 did not induce obvious histological changes in livers, kidneys, or spleens of treated animals. |
|
Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
|
References: [1] Lu Zhang, Panayotis C. Theodoropoulos, Ugur Eskiocak, et al. Selective targeting of mutant adenomatous polyposis coli (APC) in colorectal cancer. Science Translational Medicine 19 Oct 2016: Vol. 8, Issue 361, pp. 361ra140. | |
| Cas No. | 792927-06-1 | SDF | |
| Chemical Name | 1'-((4-methoxyphenyl)sulfonyl)-4-methyl-1,4'-bipiperidine | ||
| Canonical SMILES | CC1CCN(C2CCN(S(C3=CC=C(OC)C=C3)(=O)=O)CC2)CC1 | ||
| Formula | C18H28N2O3S | M.Wt | 352.49 |
| 溶解度 | ≥ 35.2mg/mL in DMSO | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.837 mL | 14.1848 mL | 28.3696 mL |
| 5 mM | 0.5674 mL | 2.837 mL | 5.6739 mL |
| 10 mM | 0.2837 mL | 1.4185 mL | 2.837 mL |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
g
μL
Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)
Calculation results:
Working concentration: mg/ml;
Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid 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 master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 39 reference(s) in Google Scholar.)
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