OTS964 |
| Catalog No.GC16511 |
OTS964 es un inhibidor de TOPK (proteÍna quinasa originada en células asesinas activada por linfocina T) activo por vÍa oral, de alta afinidad y selectivo con una IC50 de 28 nM. OTS964 también es un potente inhibidor de la cinasa dependiente de ciclina CDK11, que se une a CDK11B con una Kd de 40 nM.
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 1338545-07-5
Sample solution is provided at 25 µL, 10mM.
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OTS964{(R)-9-(4-(1-(dimethylamino)propan-2-yl)phenyl)-8-hydroxy-6-methylthieno[2,3-c] quinolin-4(5H)-one} is a potent TOPK inhibitor with an IC50 value of 28 nM. It is a dimethylated derivative of OTS514. OTS964 can inhibit TOPK kinase activity with high affinity and selectivity. TOPK (T-lymphokine-activated killer cell-originated protein kinase) is a protein that is found in a wide range of human cancers and is believed to work as an oncogene, promoting tumor growth.
It has been reported that OTS964 inhibited the growth of TOPK-positive cells with low IC50 values [A549 (31 nM), LU-99 (7.6 nM), DU4475 (53 nM), MDA-MB-231 (73 nM), T47D (72 nM), Daudi (25 nM), UM-UC-3 (32 nM), HCT-116(33nM), MKN1(38nM), MKN45(39nM), HepG2(19nM), MIAPaca-2 (30 nM), and 22Rv1 (50 nM)]. However, its growth inhibitory effect against TOPK-negative HT29 cancer cells was significantly weaker, with IC50 value of 290 nM. Intravenous administration of OTS964 at 40 mg/kg on days 1, 4, 8, 11, 15, and 18 to mice bearing LU-99 lung cancer cells, a TGI of 44% was observed on day 22 without any body weight loss. The differentiation of HSCs to amega-karyocyte population was also enhanced by OTS964 treatment 1.
References:
1. Matsuo Y, Park JH2, Miyamoto T, et al. TOPK inhibitor induces complete tumor regression in xenograft models of human cancer through inhibition of cytokinesis. ci Transl Med. 2014 Oct 22;6(259):259ra145.
| Cell experiment [2]: | |
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Cell lines |
AML-CD34+, MV4-11 and MOLM13 cell lines |
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Preparation method |
Soluble in DMSO > 10 mM. 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. |
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Reaction Conditions |
~ 48 hours |
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Applications |
There is a significant decrease in the number of colonies per well in AML-CD34+ cells treated with 10 nM of OTS514 compared to untreated cells (41 vs 73, P = 0.01). OTS514 exhibits cytotoxic activity in AML cells but not in normal CD34+ cells. OTS514 also leads to 80% and 70% increase in apoptotic cell population in MV4-11 and MOLM13 cells that carried FLT3 mutations. |
| Animal experiment [1]: | |
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Animal models |
LU-99 xenografts (female BALB/cSLC-nu/nu Mice) |
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Dosage form |
Intravenously treated with liposomal OTS964 (40 mg/kg) |
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Applications |
OTS514 induces irregular cell morphology with cytokinesis defects and significantly increases the number of LU-99 cells with the “intercellular bridge” which is one of the markers indicating impaired cell division. |
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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. |
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References: 1. Matsuo Y, Park JH2, Miyamoto T, et al. TOPK inhibitor induces complete tumor regression in xenograft models of human cancer through inhibition of cytokinesis. ci Transl Med. 2014 Oct 22;6(259):259ra145. 2. Alachkar H, Mutonga M, Malnassy G et al. T-LAK cell-originated protein kinase presents a novel therapeutic target in FLT3-ITD mutated acute myeloid leukemia. Oncotarget. 2015 Oct 20;6(32):33410-25. | |
| Cas No. | 1338545-07-5 | SDF | |
| Chemical Name | (R)-9-(4-(1-(dimethylamino)propan-2-yl)phenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one | ||
| Canonical SMILES | C[C@@H](CN(C)C)C1=CC=C(C2=C(O)C=CC3=C2C(C=CS4)=C4C(N3)=O)C=C1 | ||
| Formula | C22H22N2O2S | M.Wt | 378.49 |
| Solubility | DMF: 30 mg/ml,DMSO: 30 mg/ml,DMSO:PBS(pH 7.2) (1:2): 0.25 mg/ml | 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 | 2.6421 mL | 13.2104 mL | 26.4208 mL |
| 5 mM | 0.5284 mL | 2.6421 mL | 5.2842 mL |
| 10 mM | 0.2642 mL | 1.321 mL | 2.6421 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: >99.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 2 reference(s) in Google Scholar.)
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