KIN-59 (Synonyms: 5’-O-Tritylinosine) |
Catalog No.GC16460
One-Click Copy Product Info
|
KIN-59 is a noncompetitive inhibitor against human and bacterial recombinant thymidine phosphorylase (TPase) with IC50 values of 67 and 44µM respectively.
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 4152-77-6
Sample solution is provided at 25 µL, 10mM.
_1-3.$$$39978408@51.jpg');)
_1-9.$$$38538795@65.jpg');)
_1-9.$$$39112701@51.jpg');)
_1-7.$$$37316672@70.jpg');)
_366-372.$$$36198801@70.jpg');)
.$$$38565142@65.jpg');)
_1867-1883.$$$33248023@67.jpg');)
_eads6055.$$$39977546@45.jpg');)
_eadm9805.$$$40080571@45.jpg');)
_eadj3020.$$$39666821@45.jpg');)
_1-20.$$$39757301@28.jpg');)
_1-24.$$$38898113@28.jpg');)
_273-287.$$$36806353@46.jpg');)
_1-16.$$$37156877@44.jpg');)
_1-19.$$$37460805@44.jpg');)
_1291-1307.$$$34518654@46.jpg');)
KIN-59 is a noncompetitive inhibitor against human and bacterial recombinant thymidine phosphorylase (TPase) with IC50 values of 67 and 44µM respectively[1]. KIN-59 is a purine riboside derivative that blocks the enzyme non-competitively with thymidine or phosphate, and requires both the intact 5′-O-trityl group and the ribose–hypoxanthine scaffold for activity[2].
In vitro, KIN-59 (0–100µM) incubated muse aortic endothelial cells (MAECs) for 5 days poorly inhibited cell proliferation with an IC50 value of 78 ± 2µM. KIN-59 also dose-dependently slowed endothelial cell migration in a 16-hour wound-healing assay[3]. KIN-59 (250nmol) incubated fertilized chicken eggs with or without 10µl of TPase for 4 days. KIN-59 not only annihilated the TPase-induced angiogenesis but also efficiently inhibited the formation of normal chick chorioallantoic membrane vessels in the absence of exogenously added TPase[4]. KIN-59 (125–250μM) pretreatment on human or wild-type murine platelets for 5min before collagen, ADP, thrombin or collagen related peptide stimulation reversibly and dose-dependently suppressed induced aggregation[5].
In vivo, KIN-59 (15mg/kg) was injected subcutaneously in immunodeficient nude mice twice daily (once daily during the weekend) until day 20. KIN-59 inhibited the binding of fibroblast growth factor 2 (FGF2) to FGF receptor 1, preventing the growth and neovascularization of subcutaneous tumors induced by FGF2-transformed endothelial cells[6].
References:
[1] Liekens S, Balzarini J, Hernández A I, et al. Thymidine phosphorylase is noncompetitively inhibited by 5'-O-trityl-inosine (KIN59) and related compounds. Nucleosides Nucleotides Nucleic Acids. 2006;25(9-11):975-80.
[2] Casanova E, Hernandez A I, Priego E M, et al. 5'-O-tritylinosine and analogues as allosteric inhibitors of human thymidine phosphorylase. J Med Chem. 2006 Sep 7;49(18):5562-70.
[3] Liekens, S., Bronckaers, A., Hernández, A.I., et al. 5'-O-tritylated nucleoside derivatives: inhibition of thymidine phosphorylase and angiogenesis. Mol. Pharmacol. 70(2), 501-509 (2006).
[4] Liekens, S., Hernández, A.I., Ribatti, D., et al. The nucleoside derivative 5'-O-trityl-inosine (KIN59) suppresses thymidine phosphorylase-triggered angiogenesis via a noncompetitive mechanism of action. The Journal of Biological Chemisty 279(28), 29598-29605 (2004).
[5] Li W, Gigante A, Perez-Perez M J, et al. Thymidine phosphorylase participates in platelet signaling and promotes thrombosis. Circ Res. 2014 Dec 5;115(12):997-1006.
[6] Liekens, S., Bronckaers, A., Belleri, M., et al. The thymidine phosphorylase inhibitor 5'-O-tritylinosine (KIN-59) is an antiangiogenic multitarget fibroblast growth factor-2 antagonist. Mol. Cancer Ther. 11(4), 817-829 (2012).
| Kinase experiment [1]: | |
Preparation Method | 500μL reaction solution containing 10mM Tris-HCl pH 7.6, 1mM EDTA, 150mM NaCl, 2mM phosphate and 100μM thymidine with 0.025U enzyme TPase was incubated for 60min at room temperature. The samples taken at 0, 20, 40, 60min, 100μL aliquots were boiled, cooled and analyzed by RP-8 HPLC (267nm) to quantify thymine formation. KIN-59 (1mM, 100μM, 10μM, and 0μM) were added to the reaction mixture to test for TPase inhibition. |
Reaction Conditions | 0–1000μM; 60min |
Applications | KIN-59 inhibited TPase in a reversible, non-competitive manner with Ki value of about 39μM. |
| Cell experiment [2]: | |
Cell lines | Fetal bovine aortic endothelial GM7373 cells |
Preparation Method | Serum-starved FGFR1-overexpressing GM7373 cells and VEGFR2-overexpressing GM7373 cells were incubated with 60μM KIN-59 or vehicle for 30min, after which 10ng/mL FGF2 or 30ng/mL VEGF was added. |
Reaction Conditions | 60μM; 30min |
Applications | KIN-59 inhibited FGF2- but not VEGF-stimulated endothelial cell growth. |
| Animal experiment [2]: | |
Animal models | Female, athymic, nude nu/nu mice |
Preparation Method | Eight-week-old female, athymic, nude nu/nu mice, weighing about 25g, were inoculated subcutaneously with 200mL of serum-free DMEM containing 2×106 F2T-luc2.9 cells. KIN-59 treatment was started after 24 hours and continued till the end of the experiment. KIN-59 was administered subcutaneously at 15mg/kg, twice daily (once daily during the weekend) at a site distant from the tumor (inoculation) site. |
Dosage form | 15mg/kg; s.c; twice daily (once daily during the weekend) |
Applications | KIN-59 inhibited the binding of fibroblast growth factor 2 (FGF2) to FGF receptor 1, preventing the growth and neovascularization of subcutaneous tumors induced by FGF2-transformed endothelial cells. |
References: | |
| Cas No. | 4152-77-6 | SDF | |
| Synonyms | 5’-O-Tritylinosine | ||
| Chemical Name | 5'-O-(triphenylmethyl)-inosine | ||
| Canonical SMILES | O[C@H]1[C@@H](O)[C@H](N2C=NC3=C2N=CNC3=O)O[C@@H]1COC(C4=CC=CC=C4)(C5=CC=CC=C5)C6=CC=CC=C6 | ||
| Formula | C29H26N4O5 | M.Wt | 510.5 |
| Solubility | ≤0.3mg/ml in ethanol;16mg/ml in DMSO;5mg/ml in dimethyl formamide | 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. |
||
| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
|
1 mg | 5 mg | 10 mg |
| 1 mM | 1.9589 mL | 9.7943 mL | 19.5886 mL |
| 5 mM | 391.8 μL | 1.9589 mL | 3.9177 mL |
| 10 mM | 195.9 μL | 979.4 μL | 1.9589 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 9 reference(s) in Google Scholar.)