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| Targets |
The primary target of JNJ-10198409 is the platelet-derived growth factor receptor (PDGFR), a receptor tyrosine kinase that plays a critical role in cell proliferation, migration, and angiogenesis. JNJ-10198409 is a relatively selective, orally active, and ATP competitive PDGF-RTK inhibitor. It shows good activity against PDGFR-β kinase (IC50=4.2 nM) and PDGFR-α kinase (IC50=45 nM). The compound also has potent antiproliferative activity in six of eight human tumor cell lines (IC50<0.033 μM) and is a potent inhibitor of the c-Abl kinase (IC50=22 nM).
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| ln Vitro |
JNJ-10198409 is a strong inhibitor of c-Abl kinase (IC50=22 nM) and exhibits strong antiproliferative action (IC50<0.033 μM) against six of eight human tumor cell lines [1][2].
In vitro, JNJ-10198409 inhibits PDGFR-β kinase with an IC50 of 4.2 nM and PDGFR-α kinase with an IC50 of 45 nM. It has potent antiproliferative activity in six of eight human tumor cell lines (IC50<0.033 μM) and is a potent inhibitor of the c-Abl kinase (IC50=22 nM). The compound's activity against multiple kinase targets contributes to its antiangiogenic and tumor cell antiproliferative effects. |
| ln Vivo |
In vivo, JNJ-10198409 is an orally active PDGF-RTK inhibitor. As a dual-mechanism, antiangiogenic, and tumor cell antiproliferative agent, it would be expected to have efficacy in tumor models and fibrotic disease models. However, specific in vivo efficacy data from animal models is not detailed in the available sources. The compound is for research use only and not for therapeutic applications.
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| Enzyme Assay |
For PDGFR inhibitors, standard cell-free assays involve measuring the kinase activity of recombinant PDGFR-α and PDGFR-β using peptide substrates. The compound is incubated with the enzyme, ATP, and substrate, and phosphorylation is detected by radioactive or fluorescent methods to determine IC50 values. Selectivity is assessed by profiling against a panel of kinases.
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| Cell Assay |
For PDGFR inhibitors, standard cellular assays involve treatment of cancer cell lines or PDGFR-dependent cells with the test compound for 48-72 hours. PDGFR autophosphorylation and downstream signaling (e.g., ERK, AKT) are measured by western blot. Cell proliferation, migration, and angiogenesis assays are performed. Cell viability is measured using MTT or CellTiter-Glo assays.
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| Animal Protocol |
For in vivo evaluation of PDGFR inhibitors, standard animal models include tumor xenograft models and models of fibrosis. The compound is typically administered orally for 2-4 weeks. Tumor growth, angiogenesis markers, and tissue histology are assessed.
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| ADME/Pharmacokinetics |
Metabolism / Metabolites
Known human metabolites of JNJ-10198409 include JNJ-10198409 N-glucuronide C and JNJ-10198409 N-glucuronide B. JNJ-10198409 has a molecular weight of 325.34 and formula C18H16FN3O2. It is soluble in DMSO at 83.33 mg/mL (256.13 mM). Powder can be stored at -20°C for 3 years; in solvent at -80°C for 6 months or at -20°C for 1 month. As an orally active compound, it would be expected to have favorable oral bioavailability. |
| Toxicity/Toxicokinetics |
No detailed toxicology data is publicly available for JNJ-10198409. As a research compound targeting PDGFR, standard preclinical toxicology would be required for therapeutic development. The compound's inhibition of PDGFR signaling could have effects on normal tissues, and comprehensive safety evaluation would be needed. The compound is for research use only and not for therapeutic applications.
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| References |
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| Additional Infomation |
JNJ-10198409 is a relatively selective, orally active, and ATP competitive PDGF-RTK inhibitor with an IC50 of 2 nM. It is a dual-mechanism, antiangiogenic, and tumor cell antiproliferative agent. JNJ-10198409 has good activity against PDGFR-β kinase (IC50=4.2 nM) and PDGFR-α kinase (IC50=45 nM). No regulatory approval for therapeutic use has been identified.
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| Molecular Formula |
C18H16FN3O2
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| Molecular Weight |
325.3434
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| Exact Mass |
325.122
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| Elemental Analysis |
C, 66.45; H, 4.96; F, 5.84; N, 12.92; O, 9.84
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| CAS # |
627518-40-5
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| PubChem CID |
9797370
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| Appearance |
Light yellow to yellow solid powder
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| Density |
1.4±0.1 g/cm3
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| Boiling Point |
528.8±50.0 °C at 760 mmHg
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| Flash Point |
273.6±30.1 °C
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| Vapour Pressure |
0.0±1.4 mmHg at 25°C
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| Index of Refraction |
1.671
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| LogP |
3.91
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
24
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| Complexity |
441
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| Defined Atom Stereocenter Count |
0
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| SMILES |
COC1=C(C=C2C(=C1)CC3=C2NNC3=NC4=CC=CC(=C4)F)OC
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| InChi Key |
ZDNURMVOKAERHZ-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C18H16FN3O2/c1-23-15-7-10-6-14-17(13(10)9-16(15)24-2)21-22-18(14)20-12-5-3-4-11(19)8-12/h3-5,7-9H,6H2,1-2H3,(H2,20,21,22)
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| Chemical Name |
N-(3-fluorophenyl)-6,7-dimethoxy-1,4-dihydroindeno[1,2-c]pyrazol-3-amine
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| Synonyms |
JNJ10198409; JNJ 10198409; JNJ-10198409
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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) |
DMSO : ~83.33 mg/mL (~256.13 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (6.39 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (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 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.08 mg/mL (6.39 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (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 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.0737 mL | 15.3685 mL | 30.7371 mL | |
| 5 mM | 0.6147 mL | 3.0737 mL | 6.1474 mL | |
| 10 mM | 0.3074 mL | 1.5369 mL | 3.0737 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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