| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 50mg |
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| Targets |
KG-5 targets PDGFRβ and B-Raf as its primary molecular targets. It is a dual allosteric inhibitor that binds to these kinases and stabilizes them in their inactive conformations. In addition, the compound inhibits other kinases, including FLT3, KIT, and c-Raf. By inhibiting these key signaling molecules, KG-5 disrupts multiple oncogenic pathways involved in cell proliferation, survival, and angiogenesis. This multi-kinase inhibition profile contributes to its anti-cancer and anti-angiogenic activities.
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| ln Vitro |
KG5 (compound 6) has an EC50 value of 0.59 μM for vascular smooth muscle cells (VSMC) and 0.54 μM for endothelial cells, respectively, which means that it reduces their viability [1]. Compound 6 does not impact S259, but it specifically prevents S338 phosphorylation[1]. With Kd of 300 and 520 nM, respectively, and Flt3 and KIT of 52 and 170 nM, respectively, KG5 (compound 6) exclusively inhibits PDGFRα and β [1]. Compound 6 (KG5; 5 μM) prevents bFGF- or VEGF-stimulated endothelial cells from phosphorylating MEK and ERK [1].
In vitro, KG-5 has been demonstrated to be a potent inhibitor of PDGFRβ and B-Raf kinase activity. It arrests cancer cells in prometaphase, a stage of mitosis, leading to cell cycle arrest and subsequent cell death. The compound's ability to inhibit multiple kinases has been confirmed in biochemical and cell-based assays. It inhibits the proliferation of various cancer cell lines, including those derived from renal and pancreatic tumors. Furthermore, KG-5 has been shown to inhibit angiogenesis in vitro, as evidenced by its ability to disrupt blood vessel formation in zebrafish embryos. |
| ln Vivo |
In an orthotopic renal cell carcinoma model, KG5 (Compound 6; 100 mg/kg; oral; daily; for 26 days) therapy inhibits tumor growth [1]. Comparing KG5 (Compound 6; 50 mg/kg; intraperitoneal; twice daily) therapy to vehicle controls (mouse injection of Matrigel containing bFGF) revealed full inhibition of angiogenesis. The area under the concentration-time curve (AUC0–12h) was 14.7 μg·h/mL, T1/2 was 11.5 h, and Cmax was 3.6 μg/mL according to pharmacokinetic studies of the dosage and formulation utilized for KG5[1]. In zebrafish development, KG5 (Compound 6; 1 μM) interferes with the last stages of angiogenesis [1].
In vivo, KG-5 has demonstrated significant anti-tumor and anti-angiogenic activity. In mouse models, the compound inhibits the growth of renal and pancreatic tumors. It also inhibits angiogenesis in a mouse angiogenesis model and disrupts blood vessel formation in zebrafish embryos. These in vivo effects are consistent with its mechanism of action as a multi-kinase inhibitor targeting PDGFRβ and B-Raf, among others. The compound is orally available, which is a favorable property for its potential as a therapeutic agent. |
| Enzyme Assay |
In vitro enzyme or receptor binding (non-cell) assays for KG-5 involve measuring its inhibition of kinase activity. These assays typically use purified recombinant kinase enzymes, such as PDGFRβ, B-Raf, FLT3, or KIT, and a peptide substrate in the presence of ATP. The phosphorylation of the substrate is measured using a radioactive (e.g., 33P-ATP) or fluorescent method. The compound is incubated with the enzyme and substrate at various concentrations, and the IC50 value, representing the concentration required to inhibit 50% of the enzyme activity, is determined. These assays confirm the compound's potency and selectivity profile against its target kinases.
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| Cell Assay |
In vitro cell-based assays for KG-5 are performed using cancer cell lines that are dependent on PDGFRβ and B-Raf signaling. Cells are treated with the compound, and cell viability and proliferation are assessed using standard assays such as MTT or CCK-8. Cell cycle analysis is performed using flow cytometry to evaluate the compound's ability to arrest cells in prometaphase. The effects on downstream signaling pathways are analyzed by Western blotting to detect changes in the phosphorylation of key proteins. Anti-angiogenic activity is evaluated using endothelial cell tube formation assays.
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| Animal Protocol |
Animal/Disease Models: Male Nu/nu (nude) mice were injected with SN12C-RFP cells [1]
Doses: 100 mg/kg Route of Administration: Oral; daily; continued for 26 days Experimental Results: Prevented tumor growth in the orthotopic renal cell carcinoma model. In vivo animal experiments for KG-5 are conducted using mouse xenograft models of cancer. Immunodeficient mice are subcutaneously implanted with human tumor cells (e.g., renal or pancreatic cancer cells). When tumors reach a certain size, the mice are treated orally with KG-5, and tumor volume is measured regularly. At the end of the study, tumors are excised and analyzed for markers of proliferation, apoptosis, and angiogenesis. The compound's anti-angiogenic activity is also assessed using a mouse angiogenesis model, where the inhibition of new blood vessel formation is evaluated. |
| ADME/Pharmacokinetics |
Pharmacokinetic (PK) properties of KG-5 indicate that it is orally available. The compound has a molecular weight of 459.45 and a molecular formula of C20H16F3N7OS. It is a small molecule with physicochemical properties that support oral absorption. The compound is typically formulated for oral administration in preclinical studies. Its pharmacokinetic profile, including parameters such as half-life, bioavailability, and clearance, is determined in animal studies via LC-MS/MS analysis of plasma samples.
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| Toxicity/Toxicokinetics |
Toxicology (toxicology) data for KG-5 are characteristic of a multi-kinase inhibitor. As with other kinase inhibitors, its safety profile is an important consideration for its development. The compound's effects on normal tissues that rely on PDGFRβ and B-Raf signaling are evaluated in toxicology studies. Common toxicities associated with kinase inhibitors may include effects on the gastrointestinal tract, bone marrow, and skin. The compound is generally well-tolerated at therapeutic doses in preclinical models, but its long-term safety profile requires further evaluation.
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| References | |
| Additional Infomation |
Other information: KG-5 is a research compound with potential anti-cancer and anti-angiogenic activities. It is being investigated as a potential therapeutic agent for various cancers, including those driven by PDGFRβ and B-Raf mutations. The compound is also known as KG 5 or KG5. It is available from chemical suppliers for preclinical research purposes. Its CAS number is 877874-85-6.
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| Molecular Formula |
C20H16F3N7OS
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| Molecular Weight |
459.45
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| Exact Mass |
459.109
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| Elemental Analysis |
C, 52.28; H, 3.51; F, 12.41; N, 21.34; O, 3.48; S, 6.98
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| CAS # |
877874-85-6
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| PubChem CID |
53328059
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| Appearance |
White to off-white solid powder
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| LogP |
5.123
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
11
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
32
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| Complexity |
596
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| Defined Atom Stereocenter Count |
0
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| SMILES |
FC(C1C=C(NC2NC(C3C=CC(OC4C=C(N)N=C(SC)N=4)=CC=3)=NN=2)C=CC=1)(F)F
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| InChi Key |
CMYHZFCJPORPHY-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C20H16F3N7OS/c1-32-19-26-15(24)10-16(27-19)31-14-7-5-11(6-8-14)17-28-18(30-29-17)25-13-4-2-3-12(9-13)20(21,22)23/h2-10H,1H3,(H2,24,26,27)(H2,25,28,29,30)
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| Chemical Name |
2-methylsulfanyl-6-[4-[3-[3-(trifluoromethyl)anilino]-1H-1,2,4-triazol-5-yl]phenoxy]pyrimidin-4-amine
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| Synonyms |
KG5; KG 5; KG-5
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| HS Tariff Code |
2934.99.03.00
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: This product requires protection from light (avoid light exposure) during transportation and storage. |
| 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) |
DMSO : ~100 mg/mL (~217.65 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.44 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.1765 mL | 10.8826 mL | 21.7652 mL | |
| 5 mM | 0.4353 mL | 2.1765 mL | 4.3530 mL | |
| 10 mM | 0.2177 mL | 1.0883 mL | 2.1765 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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