| Size | Price | Stock | Qty |
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| 1mg |
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| 50mg | |||
| Other Sizes |
| Targets |
KX02 targets two distinct molecular entities: Src kinase and tubulin. Src is a non-receptor tyrosine kinase involved in cell proliferation, migration, and survival, and is frequently overactivated in cancer. KX02 inhibits Src kinase activity, thereby blocking downstream signaling pathways. The compound also binds to tubulin heterodimers and inhibits microtubule polymerization, disrupting mitotic spindle formation and leading to cell cycle arrest and apoptosis.
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| ln Vitro |
In GL261 cells, KX2-361 (0-200 nM, 24-72 hours) decreases Src autophosphorylation [1]. U87 cells are stimulated in the G2/M phase of the cell cycle by KX2-361 (0-270 nM). T98G, GL261, and U87 cell lines all exhibit indicator lights when exposed to KX2-361 (0-800 nM)[1]. Proteins that polymerize microtubules are inhibited by KX2-361 (5 µM). Keep in mind that after 270 nM, coupling effects totally end [1]. The ontological structure of entities [1].
In vitro, KX02 exhibits anti-tumor activity against glioblastoma (GBM) cell lines and induces apoptosis. The compound inhibits both Src kinase activity and tubulin polymerization, resulting in concentration-dependent inhibition of tumor cell proliferation. KX02 is effective against GBM cells, including those that are resistant to conventional chemotherapies. The compound's dual mechanism of action makes it a potent inhibitor of cancer cell growth, with synergistic effects from the combination of Src inhibition and microtubule disruption. |
| ln Vivo |
Long-term survival is achieved and the growth of orthotopic GL261 brain tumors is greatly delayed by KX2-361 [1]. KX2-361 showed substantial brain penetration in mice given the lung cancer medication (20 mg/kg), with an observed brain Cmax of 4025±319 ng/g and a total exposure (AUClast) of 5044± 15 minutes post-pregnancy 355 h ng/g[1].
In vivo, KX02 has demonstrated efficacy in a murine model of glioblastoma, providing long-term survival benefits. The compound is orally bioavailable and readily crosses the blood-brain barrier (BBB) in mice. In orthotopic GBM models, oral administration of KX02 results in significant tumor growth inhibition and prolonged survival compared to vehicle-treated controls. The compound's ability to cross the BBB is a critical feature for the treatment of brain tumors. |
| Enzyme Assay |
The non-cellular assay for KX02 involves measuring its inhibitory activity against Src kinase using in vitro kinase assays. Recombinant Src kinase is incubated with a substrate peptide and ATP in the presence of varying concentrations of KX02. The phosphorylation of the substrate is quantified using radioactive or luminescent detection methods. For tubulin polymerization inhibition, purified tubulin is incubated with KX02, and microtubule assembly is monitored by turbidity at 340 nm.
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| Cell Assay |
The cellular assay for KX02 involves treating cultured glioblastoma cells with the compound and measuring its effects on cell viability, proliferation, and apoptosis. Cells are treated with KX02 at various concentrations, and cell viability is assessed using MTT or CellTiter-Glo assays. Apoptosis is measured by flow cytometry using Annexin V/PI staining. Src phosphorylation and tubulin polymerization are assessed by Western blotting and immunofluorescence microscopy.
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| Animal Protocol |
In the in vivo efficacy study, immunocompromised mice are implanted orthotopically with human glioblastoma cells. KX02 is administered orally at various doses daily for several weeks. Tumor growth is monitored by bioluminescence imaging or MRI. Survival is recorded as the primary endpoint. At the end of the study, brains are harvested for histological examination and pharmacokinetic analysis.
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| ADME/Pharmacokinetics |
KX02 has a molecular weight of 405.5 and a molecular formula of C₂₄H₂₄FN₃O₂. The compound is soluble in DMSO but not in water. It shows good oral bioavailability and readily crosses the BBB in mice. KX02 should be stored at 4°C, protected from light. Stock solutions should be stored in aliquoted, tightly sealed vials and used within 1 month.
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| Toxicity/Toxicokinetics |
KX02 is generally well-tolerated in preclinical studies at therapeutically effective doses. In murine models, the compound does not cause significant weight loss or overt toxicity at doses that produce antitumor efficacy. Comprehensive toxicology data are limited to preclinical findings. KX02 is not approved for clinical use and is strictly a research compound.
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| References | |
| Additional Infomation |
KX2-361, a Src/tubulin inhibitor, is a lipophilic, orally effective inhibitor of Src kinase activity and tubulin polymerization with potential antitumor activity. After oral administration, KX2-361 binds to and inhibits Src kinase activity, thereby suppressing downstream signaling and the proliferation of Src kinase-expressing tumor cells. KX2-361 also binds to tubulin heterodimers and inhibits microtubule polymerization, thereby disrupting microtubule formation, mitosis, and cell proliferation. Src is a non-receptor tyrosine kinase that is overexpressed in various tumor cell types and plays a crucial role in tumor cell proliferation, angiogenesis, migration, and metastasis.
KX02 (KX2-361) is a dual Src/tubulin inhibitor that has been studied for the treatment of glioblastoma. Its ability to cross the blood-brain barrier and its oral bioavailability make it a promising candidate for brain tumor research. The compound has been evaluated in preclinical studies and has shown long-term survival benefits in murine models of glioblastoma. KX02 represents a novel approach to targeting glioblastoma through the combined inhibition of Src kinase and microtubule dynamics. |
| Molecular Formula |
C24H24FN3O2
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|---|---|
| Molecular Weight |
405.4734
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| Exact Mass |
405.185
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| CAS # |
897016-26-1
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| Related CAS # |
897016-26-1;1571072-87-1 (besylate);
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| PubChem CID |
11545920
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| Appearance |
White to off-white solid powder
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| Density |
1.2±0.1 g/cm3
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| Boiling Point |
660.1±55.0 °C at 760 mmHg
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| Flash Point |
353.0±31.5 °C
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| Vapour Pressure |
0.0±2.0 mmHg at 25°C
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| Index of Refraction |
1.598
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| LogP |
2
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
30
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| Complexity |
535
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
CMKKPJNMYLOUCE-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C24H24FN3O2/c25-21-3-1-2-18(14-21)16-27-24(29)15-22-7-4-20(17-26-22)19-5-8-23(9-6-19)28-10-12-30-13-11-28/h1-9,14,17H,10-13,15-16H2,(H,27,29)
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| Chemical Name |
N-[(3-fluorophenyl)methyl]-2-[5-(4-morpholin-4-ylphenyl)pyridin-2-yl]acetamide
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| Synonyms |
KX-2-361 KX 02 KX2-361 KX02 KX-02KX 2-361
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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 | 2.4663 mL | 12.3314 mL | 24.6627 mL | |
| 5 mM | 0.4933 mL | 2.4663 mL | 4.9325 mL | |
| 10 mM | 0.2466 mL | 1.2331 mL | 2.4663 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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