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| Targets |
JTE-952 targets the colony-stimulating factor-1 receptor (CSF-1R, also known as cFMS), a type III receptor tyrosine kinase. CSF-1R is activated by its ligands, CSF-1 and IL-34, and plays critical roles in the survival, proliferation, and differentiation of macrophages, osteoclasts, and other myeloid cells. By inhibiting CSF-1R, JTE-952 modulates macrophage function and has potential applications in inflammatory and autoimmune diseases. The compound has IC50 values of 13 nM for CSF1R and 261 nM for TrkA, demonstrating selectivity for CSF-1R. JTE-952 is a Type II inhibitor that binds to the inactive conformation of the kinase.
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| ln Vitro |
JTE-952 demonstrates potent in vitro activity as a CSF-1R inhibitor. The compound has IC50 values of 13 nM for CSF1R and 261 nM for TrkA, demonstrating selectivity for CSF-1R. Its activity is concentration-dependent, with potent inhibition observed at nanomolar concentrations. JTE-952 is a Type II selective inhibitor of CSF-1R. The compound's potency and selectivity make it a valuable tool for studying CSF-1R biology and evaluating CSF-1R inhibition as a therapeutic strategy for inflammatory and autoimmune diseases. The compound's in vitro activity has been characterized in kinase assays and cell-based systems.
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| ln Vivo |
In a mouse model of collagen-induced arthritis (CIA model), JTE-952 (3 mg/kg, oral, once daily) treatment decreases the overall progression of clinical scores, including inflammation and bone degradation [1].
In vivo, JTE-952 has demonstrated efficacy in a mouse collagen-induced model of arthritis. As an orally bioactive CSF-1R inhibitor, the compound modulates macrophage function and reduces inflammation in autoimmune disease models. JTE-952 is effective against a mouse collagen-induced model of arthritis. The compound's oral bioavailability makes it suitable for convenient dosing in research settings. Its in vivo efficacy in arthritis models supports its potential for inflammatory disease research. Comprehensive in vivo efficacy data have been reported in research publications. |
| Enzyme Assay |
In vitro kinase assays for JTE-952 involve measuring the inhibition of CSF-1R kinase activity. Recombinant CSF-1R kinase is incubated with varying concentrations of the test compound, ATP, and a peptide substrate. The transfer of the phosphate group from ATP to the substrate is quantified using radioactive [33P]-ATP or by detecting phosphorylated peptide using a luminescent method such as the ADP-Glo assay. IC50 values are calculated by plotting percent inhibition against compound concentration using non-linear regression analysis. The compound has IC50 values of 13 nM for CSF1R and 261 nM for TrkA. Selectivity assays compare the compound's activity against a panel of other kinases. Each concentration is typically tested in duplicate or triplicate.
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| Cell Assay |
In vitro cellular assays for JTE-952 are performed using cell lines that express CSF-1R, such as macrophages or CSF-1R-transfected cells. Cells are treated with varying concentrations of the compound for defined time periods. CSF-1R phosphorylation and downstream signaling (e.g., ERK, AKT) are assessed by Western blot using phospho-specific antibodies. Cell proliferation and survival are measured using MTT or CellTiter-Glo assays. Macrophage differentiation and function can be assessed using appropriate assays. Cytotoxicity is assessed in parallel using standard viability assays to ensure that observed effects are not due to cell death. IC50 values for inhibition of CSF-1R phosphorylation or cell proliferation are calculated from dose-response curves.
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| Animal Protocol |
Animal/Disease Models: Collagen-induced arthritis mouse model (CIA model) [1].
Doses: 3 mg/kg. Doses: Orally, one time/day. Experimental Results: diminished overall progression of clinical scores, including inflammation and bone erosion. In vivo animal studies for JTE-952 are conducted using rodent models of inflammatory and autoimmune diseases, particularly the mouse collagen-induced arthritis model. The compound is administered via oral gavage at various doses and schedules. Arthritis severity is assessed by clinical scoring of paw swelling and inflammation. Joint histopathology is performed to assess inflammation, cartilage destruction, and bone erosion. Inflammatory cytokine levels are measured in serum and joint tissues. Pharmacokinetic studies assess drug concentrations in plasma and tissues. Animals are monitored for clinical signs and body weight. Efficacy is expressed as reduction in arthritis severity and improvement in histopathological parameters compared to vehicle-treated controls. |
| ADME/Pharmacokinetics |
Pharmacokinetic properties of JTE-952 have been characterized in preclinical studies. The compound has a molecular formula of C30H34N2O6 and a molecular weight of 518.60 g/mol. It is orally bioactive, making it suitable for convenient dosing in research settings. Comprehensive pharmacokinetic parameters including half-life, volume of distribution, clearance, and oral bioavailability have been characterized in animal models. The compound's pharmacokinetic profile supports its use in preclinical studies of inflammatory and autoimmune diseases. Detailed pharmacokinetic data are available from research publications.
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| Toxicity/Toxicokinetics |
JTE-952 is intended for laboratory research use only and has not undergone comprehensive clinical toxicology testing. As a CSF-1R inhibitor that modulates macrophage function, the compound would be expected to have effects on immune function and inflammation. Standard in vitro cytotoxicity assays in cell lines are typically performed alongside efficacy studies to rule out nonspecific toxicity. In vivo, animals are monitored for signs of toxicity including body weight changes, behavioral abnormalities, and clinical observations. Comprehensive toxicological characterization including genotoxicity and repeated-dose toxicity studies has been conducted as part of preclinical development. The compound is not approved for human use and is strictly intended for research purposes.
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| References | |
| Additional Infomation |
JTE-952 is a potent, orally bioactive, Type II selective inhibitor of CSF-1R/cFMS with IC50 values of 13 nM for CSF1R and 261 nM for TrkA. It is effective against a mouse collagen-induced model of arthritis. The compound has a molecular formula of C30H34N2O6 and a molecular weight of 518.60 g/mol. JTE-952 has not entered clinical trials and has not received regulatory approval for any indication. It is available from research chemical suppliers for non-clinical research purposes only. JTE-952 is a valuable research tool for studying CSF-1R biology and developing new therapies for inflammatory and autoimmune diseases.
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| Molecular Formula |
C30H34N2O6
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| Molecular Weight |
518.6008
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| Exact Mass |
518.241
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| CAS # |
1255303-54-8
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| PubChem CID |
49806372
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| Appearance |
White to off-white solid powder
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| LogP |
2.9
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
12
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| Heavy Atom Count |
38
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| Complexity |
736
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| Defined Atom Stereocenter Count |
1
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| SMILES |
O(C1C([H])=C([H])C(=C([H])C=1OC([H])([H])[H])C1([H])C([H])([H])N(C(C2C([H])=C(C([H])([H])OC([H])([H])[C@]([H])(C([H])([H])O[H])O[H])C([H])=C([H])N=2)=O)C1([H])[H])C([H])([H])C1C([H])=C([H])C(=C([H])C=1[H])C1([H])C([H])([H])C1([H])[H]
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| InChi Key |
LTTJGQBDGMNWHJ-SANMLTNESA-N
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| InChi Code |
InChI=1S/C30H34N2O6/c1-36-29-13-24(8-9-28(29)38-18-20-2-4-22(5-3-20)23-6-7-23)25-14-32(15-25)30(35)27-12-21(10-11-31-27)17-37-19-26(34)16-33/h2-5,8-13,23,25-26,33-34H,6-7,14-19H2,1H3/t26-/m0/s1
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| Chemical Name |
[3-[4-[(4-cyclopropylphenyl)methoxy]-3-methoxyphenyl]azetidin-1-yl]-[4-[[(2S)-2,3-dihydroxypropoxy]methyl]pyridin-2-yl]methanone
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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 Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture and light. |
| 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 (~192.83 mM)
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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 | 1.9283 mL | 9.6413 mL | 19.2827 mL | |
| 5 mM | 0.3857 mL | 1.9283 mL | 3.8565 mL | |
| 10 mM | 0.1928 mL | 0.9641 mL | 1.9283 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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