| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
KIN59 targets thymidine phosphorylase (TPase, also known as platelet-derived endothelial cell growth factor, PD-ECGF) as a noncompetitive/allosteric inhibitor. It also inhibits FGF2-stimulated cell growth by suppressing the expression of p-FGFR1 and p-Akt. The compound may have additional effects on FGF2 signaling.
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| ln Vitro |
For GM7373 cells treated with FGF2 (30 ng/mL) and PBS (10%), respectively, KIN59 (0-100 µM; 24 h) suppresses cell growth with IC50 values of 5.8 and 63 µM [1]. In FGFR1-overexpressing GM7373-FGFR1 cells stimulated by FGF2 (10 ng/mL), KIN59 (60 µM; 30 min) suppresses the production of P-Akt and p-FGFR1 [1]. KIN59 has IC50 values of 44 μM and 67 μM, respectively, which indicate its ability to inhibit human thymidine phosphorylase (TPase) and recombinant bacteria (E. coli) [2].
In vitro, KIN59 (1-100 uM) inhibits the enzymatic activity of human and bacterial recombinant thymidine phosphorylase in a noncompetitive manner. It blocks FGF2-induced proliferation of endothelial cells and fibroblasts, with inhibition of FGFR1 phosphorylation (p-FGFR1) and Akt phosphorylation (p-Akt). The compound demonstrates antiproliferative effects on FGF2-driven cancer cell lines. |
| ln Vivo |
In mice, anticancer activity is demonstrated by KIN59 (15 mg/kg; subcutaneous injection; twice daily beginning on day 2 for 20 days) [1].
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| Enzyme Assay |
For non-cellular TPase inhibition, purified recombinant human thymidine phosphorylase (10-100 ng) is incubated with the substrate thymidine (1 mM) in phosphate buffer (pH 7.4) in the presence of varying concentrations of KIN59 (0.01-1000 uM). The reaction is stopped by heating, and the product (thymine) is quantified by reverse-phase HPLC or by measuring absorbance at 300 nm. Lineweaver-Burk plots are used to confirm noncompetitive/allosteric inhibition.
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| Cell Assay |
Cell Proliferation Assay[1]
Cell Types: GM7373 cells Tested Concentrations: 0-100 µM Incubation Duration: 24 h Experimental Results: Inhibited FGF2 (30 ng /mL)-induced proliferation of bovine macrovascular endothelial GM7373 cells in a dose-dependent manner with IC50 values of 5.8, 63 µM for FGF2 and PBS, respectively. Western Blot Analysis[1] Cell Types: GM7373-FGFR1, GM7373-VEGFR2 cells Tested Concentrations: 60 µM Incubation Duration: 30 min Experimental Results: Inhibited FGFR1 phosphorylation and Akt activation triggered by FGF2 in FGFR1-overexpressing GM7373-FGFR1 cells, demonstrated minor inhibitors on VEGF-mediated VEGFR2 phosphorylation and Akt activation in GM7373 cells overexpressing VEGFR2. For cell-based assays, human umbilical vein endothelial cells (HUVEC) or FGF2-stimulated fibroblasts are seeded in 96-well plates and treated with KIN59 (1-100 uM) for 24-72 hours. Cell proliferation is measured by BrdU incorporation or MTT. FGF2 signaling is assessed by Western blotting for phospho-FGFR1 (p-FGFR1) and phospho-Akt (p-Akt). |
| Animal Protocol |
Animal/Disease Models: Eightweeks old female, 25 g, athymic, nude nu/nu (nude) mice (F2T-luc2.9 cells)[1]
Doses: 15 mg/kg Route of Administration: Sc; twice (two times) daily from day 2 (one time/day during the weekend) at a site distant from the tumor (inoculation) site for 20 days Experimental Results: Caused a significant inhibition in the rate of tumor growth. For in vivo evaluation, the compound is evaluated in murine models of angiogenesis and cancer. Female C57BL/6 mice with subcutaneous tumor xenografts (e.g., FGF2-driven tumors or colon cancer cells) are dosed with KIN59 (10-50 mg/kg) intraperitoneally or orally once daily for 14-28 days. Tumor volume is measured twice weekly. In Matrigel plug assays, KIN59 is administered systemically, and hemoglobin content in plugs is measured to assess anti-angiogenic activity. |
| ADME/Pharmacokinetics |
Pharmacokinetic data for KIN59 (MW 510.54) are limited. As a trityl-protected nucleoside, it is likely to have moderate oral bioavailability. The trityl group may protect the compound from rapid metabolism, but detailed PK parameters (Cmax, AUC, t½) are not publicly available.
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| Toxicity/Toxicokinetics |
Toxicity data for KIN59 are limited. In preclinical studies, the compound appears to be well tolerated at effective doses with no significant weight loss or behavioral changes. In vitro cytotoxicity assessments in non-cancer cell lines show a favorable safety window.
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| References |
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| Additional Infomation |
KIN59 is a research-grade compound, not approved for human therapy. It is valuable for studying thymidine phosphorylase function in angiogenesis and tumor progression. The compound may have potential as an anticancer agent by inhibiting both TPase and FGF2 signaling. No clinical trials are registered.
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| Molecular Formula |
C29H26N4O5
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| Molecular Weight |
510.54
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| Exact Mass |
510.19
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| CAS # |
4152-77-6
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| PubChem CID |
135526599
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| Appearance |
White to off-white solid powder
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| LogP |
2.747
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
7
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| Heavy Atom Count |
38
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| Complexity |
793
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| Defined Atom Stereocenter Count |
4
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| SMILES |
C1=CC=C(C=C1)C(C2=CC=CC=C2)(C3=CC=CC=C3)OC[C@@H]4[C@H]([C@H]([C@@H](O4)N5C=NC6=C5N=CNC6=O)O)O
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| InChi Key |
YEPZMZDCXFRHCL-ZYWWQZICSA-N
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| InChi Code |
InChI=1S/C29H26N4O5/c34-24-22(38-28(25(24)35)33-18-32-23-26(33)30-17-31-27(23)36)16-37-29(19-10-4-1-5-11-19,20-12-6-2-7-13-20)21-14-8-3-9-15-21/h1-15,17-18,22,24-25,28,34-35H,16H2,(H,30,31,36)/t22-,24-,25-,28-/m1/s1
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| Chemical Name |
9-[(2R,3R,4S,5R)-3,4-dihydroxy-5-(trityloxymethyl)oxolan-2-yl]-1H-purin-6-one
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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) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.9587 mL | 9.7936 mL | 19.5871 mL | |
| 5 mM | 0.3917 mL | 1.9587 mL | 3.9174 mL | |
| 10 mM | 0.1959 mL | 0.9794 mL | 1.9587 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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