| Size | Price | Stock | Qty |
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| 10mg |
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| 25mg |
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| 50mg |
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| 100mg |
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| 250mg |
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| 500mg |
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| Other Sizes |
| Targets |
The primary target of KN1022 is the platelet-derived growth factor receptor (PDGFR), a receptor tyrosine kinase that plays a critical role in cell proliferation, migration, and angiogenesis. PDGFR is activated by the binding of platelet-derived growth factor (PDGF), leading to receptor dimerization and autophosphorylation. KN1022 inhibits the phosphorylation of PDGFR, thereby blocking the activation of downstream signaling pathways. The compound inhibits PDGFR phosphorylation with an IC50 of approximately 0.24-0.26 µM. By inhibiting PDGFR, KN1022 can modulate various cellular processes, including proliferation, migration, and angiogenesis. The compound's selectivity for PDGFR over other kinases is an important feature for its use as a research tool. KN1022 is a prototype quinazoline-based inhibitor, and its structure serves as a starting point for the development of more potent and selective PDGFR inhibitors.
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| ln Vitro |
In vitro, KN1022 inhibits PDGFR phosphorylation with an IC50 of approximately 0.24-0.26 µM. This inhibition leads to the blockade of downstream signaling pathways, including the PI3K/Akt and MAPK pathways, which are involved in cell proliferation, survival, and migration. In PDGFR-expressing cell lines, KN1022 inhibits cell proliferation and migration. The compound's in vitro activity is well-characterized and forms the basis for its use in PDGFR signaling research. KN1022 is a valuable tool for studying the role of PDGFR in various cellular processes, including angiogenesis, wound healing, and cancer.
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| ln Vivo |
In vivo, KN1022 has been evaluated in animal models of diseases where PDGFR signaling is implicated, including cancer and fibrosis. The compound inhibits PDGFR-mediated cellular processes in vivo. By blocking PDGFR phosphorylation, KN1022 can reduce tumor growth, angiogenesis, and fibrosis. The compound's in vivo activity is attributed to its ability to inhibit PDGFR signaling. Further studies are needed to fully characterize the compound's in vivo pharmacokinetics and efficacy in different disease models. The compound's selectivity for PDGFR is a key advantage for its use in vivo, as it minimizes off-target effects.
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| Enzyme Assay |
Cell-free kinase assays with KN1022 are performed using purified PDGFR kinase domain or immunoprecipitated PDGFR from cell lysates. The compound is incubated with ATP and peptide substrates at varying concentrations. Kinase activity is measured by radioactive phosphate incorporation or luminescent ADP detection to determine IC50 values. These cell-free assays are essential for characterizing the potency and selectivity of KN1022 as a PDGFR inhibitor. The compound's activity against other kinases is assessed to determine its selectivity profile. The cell-free assay data provide a quantitative measure of the compound's inhibitory activity and are used to compare its potency with other PDGFR inhibitors. These data are also important for understanding the structure-activity relationships (SAR) of the compound and for guiding the design of more potent and selective inhibitors.
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| Cell Assay |
In cellular assays, PDGFR-expressing cell lines are treated with KN1022 at various concentrations. PDGFR phosphorylation is assessed by Western blot using phospho-specific antibodies. Cell proliferation, migration, and survival are evaluated using MTT, wound healing, and apoptosis assays. These cellular assays are crucial for understanding the functional consequences of PDGFR inhibition and for validating the compound's activity as a PDGFR inhibitor. The compound's potency in cellular systems is consistent with its activity in cell-free assays. The results from these assays provide valuable information for the use of KN1022 in research applications.
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| Animal Protocol |
In vivo efficacy of KN1022 is evaluated in rodent models of PDGFR-driven diseases, including tumor xenografts and fibrosis models. The compound is administered via oral gavage or intraperitoneal injection. Tumor growth, fibrosis markers, and PDGFR phosphorylation in tissues are monitored. The compound's ability to inhibit PDGFR signaling in vivo is assessed by measuring the phosphorylation of PDGFR and downstream targets in tumor or tissue samples. These in vivo studies are essential for confirming the compound's efficacy in a physiologically relevant context and for guiding the development of PDGFR inhibitors as therapeutic agents.
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| ADME/Pharmacokinetics |
Pharmacokinetic properties of KN1022 are determined in preclinical studies. Parameters including oral bioavailability, half-life, and tissue distribution are evaluated following administration in rodents using LC-MS/MS analysis. The compound's bioavailability and half-life are important for determining the appropriate dosing regimen for in vivo studies. The compound's tissue distribution is also assessed to ensure that it reaches its target tissues. The pharmacokinetic data obtained from these studies are essential for designing appropriate dosing regimens and for interpreting the results of efficacy and toxicity studies.
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| Toxicity/Toxicokinetics |
Standard toxicology studies in rodents assess the safety profile of KN1022. Acute and repeat-dose toxicity, organ histopathology, hematological parameters, and clinical chemistry are evaluated. The compound's toxicity may include effects on the cardiovascular system, gastrointestinal tract, and other organs, given its kinase inhibitory activity. The compound is for research use only and has not been evaluated for human safety. Standard safety precautions should be followed when handling KN1022, including the use of appropriate personal protective equipment and adherence to institutional safety guidelines.
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| References | |
| Additional Infomation |
KN1022 (CAS 205255-11-4) is a research compound for laboratory use only. It is a selective inhibitor of PDGFR phosphorylation with an IC50 of approximately 0.24-0.26 µM. The compound is a quinazoline-based prototype PDGFR inhibitor used for SAR studies and cellular signaling research. KN1022 is not approved for human therapeutic use and is intended for research purposes only. It should be stored according to the manufacturer's recommendations, typically at -20°C, to ensure stability. When handling KN1022, researchers should follow standard safety protocols for handling chemical reagents, including the use of appropriate personal protective equipment and working in a well-ventilated area.
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| Molecular Formula |
C21H22N6O5
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| Molecular Weight |
438.436583995819
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| Exact Mass |
438.165
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| CAS # |
205255-11-4
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| PubChem CID |
9911005
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| Appearance |
Typically exists as solid at room temperature
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| LogP |
2.4
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
8
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
32
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| Complexity |
647
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| Defined Atom Stereocenter Count |
0
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| SMILES |
COC1=C(C=C2C(=C1)C(=NC=N2)N3CCN(CC3)C(=O)NC4=CC=C(C=C4)[N+](=O)[O-])OC
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| InChi Key |
ZIFCMJKHIXABHJ-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C21H22N6O5/c1-31-18-11-16-17(12-19(18)32-2)22-13-23-20(16)25-7-9-26(10-8-25)21(28)24-14-3-5-15(6-4-14)27(29)30/h3-6,11-13H,7-10H2,1-2H3,(H,24,28)
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| Chemical Name |
4-(6,7-dimethoxyquinazolin-4-yl)-N-(4-nitrophenyl)piperazine-1-carboxamide
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| Synonyms |
KN-1022KN1022KN 10221-Piperazinecarboxamide, 4-(6,7-dimethoxy-4-quinazolinyl)-N-(4-nitrophenyl)-
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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 | 2.2808 mL | 11.4041 mL | 22.8081 mL | |
| 5 mM | 0.4562 mL | 2.2808 mL | 4.5616 mL | |
| 10 mM | 0.2281 mL | 1.1404 mL | 2.2808 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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