LLL12 |
Catalog No.GC69384
One-Click Copy Product Info
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LLL12 is a specific small molecule inhibitor of signal transducer and activator of transcription 3 (STAT3) that inhibits STAT3 phosphorylation.
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 1260247-42-4
Sample solution is provided at 25 µL, 10mM.
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LLL12 is a specific small molecule inhibitor of signal transducer and activator of transcription 3 (STAT3) that inhibits STAT3 phosphorylation[1]. STAT3 is a key signal transducer and transcriptional activator, involved in various biological functions such as cell cycle regulation, survival and apoptosis, immune modulation, metabolic processes, and tumor progression. Its abnormal activation is closely related to the occurrence and development of various diseases[2]. LLL12 effectively suppresses the growth, migration, and invasion of tumor cells by inhibiting the activity of STAT3 and is commonly used in cancer research[3-4].
In vitro, the IC50 values of LLL12 for RD2, RH30, and U2OS cells were 2.85μM, 0.47μM, and 1μM, respectively. After 72 hours of treatment, LLL12 significantly inhibited cell proliferation[5]. LLL12 (5 or 10μM; 2h)inhibits STAT3 signaling and blocks the anti-apoptotic activity of IL-6 in human liver cancer cells[6]. LLL12 (0.1, 1.0, 0.1 and 0.01µM for A2780, SKOV3, CAOV-3 and OVCAR5, respectively; 72h) enhanced the inhibitory effect of Cisplatin and Paclitaxel on ovarian cancer cell formation, migration, and growth[4].
In vivo, LLL12 (5mg/kg/day for 13 days; i.p.) suppressed STAT3 phosphorylation and resulted in a significant reduction in tumor volume and tumor mass in the OS-33 and SJSA xenografted mice, relative to the vehicle[7].
References:
[1] Lin, L., Hutzen, B., Li, P. K., Ball, S., Zuo, M., DeAngelis, S., Foust, E., Sobo, M., Friedman, L., Bhasin, D., Cen, L., Li, C., & Lin, J. (2010). A novel small molecule, LLL12, inhibits STAT3 phosphorylation and activities and exhibits potent growth-suppressive activity in human cancer cells. Neoplasia (New York, N.Y.), 12(1), 39–50.
[2] Ma, J. H., Qin, L., & Li, X. (2020). Role of STAT3 signaling pathway in breast cancer. Cell communication and signaling : CCS, 18(1), 33.
[3] Zuo, M., Li, C., Lin, J., & Javle, M. (2015). LLL12, a novl small inhibitor targeting STAT3 for hepatocellular carcinoma therapy. Oncotarget, 6(13), 10940–10949.
[4] Zhang, R., Chen, X., Fu, S., Xu, L., & Lin, J. (2020). A small molecule STAT3 inhibitor, LLL12, enhances cisplatin and paclitaxel mediated inhibition of cell growth and migration in human ovarian cancer cells. Oncology reports, 44(3), 1224–1232.
[5] Yu, W., Xiao, H., Lin, J., & Li, C. (2013). Discovery of novel STAT3 small molecule inhibitors via in silico site-directed fragment-based drug design. Journal of medicinal chemistry, 56(11), 4402–4412.
[6] Liu, Y., Li, P. K., Li, C., & Lin, J. (2010). Inhibition of STAT3 signaling blocks the anti-apoptotic activity of IL-6 in human liver cancer cells. The Journal of biological chemistry, 285(35), 27429–27439.
[7] Onimoe, G. I., Liu, A., Lin, L., Wei, C. C., Schwartz, E. B., Bhasin, D., Li, C., Fuchs, J. R., Li, P. K., Houghton, P., Termuhlen, A., Gross, T., & Lin, J. (2012). Small molecules, LLL12 and FLLL32, inhibit STAT3 and exhibit potent growth suppressive activity in osteosarcoma cells and tumor growth in mice. Investigational new drugs, 30(3), 916–926.
| Cell experiment [1]: | |
Cell lines | Hep3B and SNU-398 cells |
Preparation Method | Hep3B cells were cultured in Minimum Essential Medium, Eagle (MEM) supplemented with 10% fetal bovine serum (FBS) and 1% penicillin/streptomycin. SNU-398 were cultured in RPMI 1640 medium (ATCC) supplemented with 10% fetal bovine serum (FBS) and 1% penicillin/streptomycin. After treatment with serum-free medium for 24h, cells were pretreated with 5 or 10μM LLL12 for 2h followed by 50ng/ml of IL-6 for 30min. Then cells were collected for Western Blot and Immunofluorescence. |
Reaction Conditions | 5 or 10μM; 2h |
Applications | LLL12 inhibit of STAT3 signaling and blocks the anti-apoptotic activity of IL-6 in human liver cancer cells. |
| Animal experiment [2]: | |
Animal models | Female athymic nude mice |
Preparation Method | SJSA cells (1×107) in Matrigel were injected subcutaneously into the flank region of four to five week-old female athymic nude mice. After tumors developed, the mice were randomly sorted into three treatment groups consisting of six mice per group: DMSO vehicle group, 5mg/kg LLL12, and 50mg/kg FLLL32. Tumor growth was determined by measuring the major (L) and minor (W) diameter with a caliper. After 14 days of treatment, tumors were harvested from dead mice, frozen in liquid nitrogen, and stored at −80°C. Western blotting was then performed on tumor tissue homogenates to examine the expression of STAT3 phosphorylation and the induction of apoptosis in vehicle and inhibitor treated mice. |
Dosage form | 5mg/kg/day for 13 days; i.p. |
Applications | LLL12 suppressed STAT3 phosphorylation and resulted in a significant reduction in tumor volume and tumor mass in the OS-33 and SJSA xenografted mice. |
References: | |
| Cas No. | 1260247-42-4 | SDF | |
| Formula | C14H9NO5S | M.Wt | 303.29 |
| Solubility | DMSO : 100 mg/mL (329.72 mM; ultrasonic and warming and heat to 60°C) | Storage | 4°C, protect from light |
| 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 | 3.2972 mL | 16.4859 mL | 32.9717 mL |
| 5 mM | 659.4 μL | 3.2972 mL | 6.5943 mL |
| 10 mM | 329.7 μL | 1.6486 mL | 3.2972 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 saline, 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% Appearance: A solid
- COA (Certificate of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 30 reference(s) in Google Scholar.)