| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
|
| Targets |
ARRY-382 targets colony-stimulating factor 1 receptor (CSF1R/c-Fms), a receptor tyrosine kinase expressed primarily on macrophages and monocytes. By inhibiting CSF1R signaling, ARRY-382 blocks the survival, proliferation, and recruitment of immunosuppressive tumor-associated macrophages, thereby enhancing anti-tumor immunity.
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|---|---|
| ln Vitro |
In vitro, ARRY-382 potently inhibits CSF1R/c-Fms kinase activity with an IC50 of 9 nM. It effectively blocks CSF-1-induced proliferation and survival of macrophages, reduces the secretion of immunosuppressive cytokines (e.g., IL-10, TGF-beta), and enhances T-cell activation in co-culture systems.
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| Enzyme Assay |
A biochemical kinase inhibition assay is performed using purified CSF1R/c-Fms enzyme (0.5-2 nM) and a peptide substrate in the presence of ATP (10 uM). ARRY-382 (0.01-1000 nM) is incubated with the reaction mixture for 30-60 min at room temperature. Kinase activity is measured using a luminescence-based ADP detection kit or by radioactive 33P-ATP incorporation, and IC50 is calculated by curve fitting.
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| Cell Assay |
Human peripheral blood mononuclear cells (PBMCs) or isolated monocytes are differentiated into macrophages in the presence of M-CSF (10-50 ng/mL) for 5-7 days. Cells are then treated with ARRY-382 (0.1-1000 nM) for 1-24 h. Cell viability is assessed by MTT assay, and cytokine levels (e.g., IL-10, IL-6, TNF-alpha) in the supernatant are measured by ELISA. For co-culture studies, macrophages are co-cultured with T-cells, and T-cell activation markers (e.g., IFN-gamma, CD69) are analyzed by flow cytometry.
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| Animal Protocol |
In vivo efficacy is evaluated in syngeneic tumor mouse models (e.g., MC38 colon carcinoma or B16 melanoma). ARRY-382 is administered orally at 10-60 mg/kg once daily for 10-21 days. Tumor volume is measured every 2-3 days, and tumor-infiltrating immune cells are analyzed by flow cytometry to assess tumor-associated macrophage (TAM) reduction and CD8+ T-cell increase.
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| ADME/Pharmacokinetics |
ARRY-382 is orally bioavailable with good plasma exposure. In preclinical studies, it exhibits a half-life (t1/2) of approximately 4-8 h in rodents, with Cmax achieved within 1-3 h post-dose (Tmax). Plasma protein binding is moderate to high. Clearance occurs primarily via hepatic metabolism, likely involving CYP450 enzymes.
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| Toxicity/Toxicokinetics |
Preclinical toxicology studies have shown ARRY-382 to be generally well-tolerated. Potential adverse effects may include mild hepatotoxicity, reversible changes in serum alkaline phosphatase (ALP) or ALT, and slight myelosuppression due to CSF1R inhibition. No significant target-independent toxicities were reported. Comprehensive safety profiling would be required for clinical advancement.
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| References | |
| Additional Infomation |
ARRY-382, a cFMS tyrosine kinase inhibitor, is a small-molecule oral drug that inhibits the colony-stimulating factor-1 receptor (CSF1R; cFMS) and possesses potential antitumor activity. ARRY-382 binds to cFMS and inhibits its activity. By blocking the colony-stimulating factor-1 (CSF-1)-cFMS signaling pathway, this drug may inhibit the proliferation of cFMS-overexpressing tumor cells. cFMS is a tyrosine kinase receptor that is overexpressed in certain tumor cell types and plays an important role in the regulation of macrophage differentiation and cell proliferation.
ARRY-382 has completed Phase 1 clinical trials for advanced solid tumors. It was evaluated as monotherapy and in combination with anti-PD-1 immunotherapy. While initial development has been paused, the compound remains a valuable research tool for studying CSF1R inhibition and tumor-associated macrophage biology. |
| Molecular Formula |
C32H36N8O2
|
|---|---|
| Molecular Weight |
564.680645942688
|
| Exact Mass |
564.296
|
| CAS # |
1313407-95-2
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| PubChem CID |
67259771
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| Appearance |
Solid powder
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| LogP |
3.9
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| Hydrogen Bond Donor Count |
1
|
| Hydrogen Bond Acceptor Count |
7
|
| Rotatable Bond Count |
9
|
| Heavy Atom Count |
42
|
| Complexity |
913
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
O(C1C=CN2C(C=1)=NC=C2C(NC1=CC=CC2=C1C(C1CC1)=NN2CC1C=CC=C(C)N=1)=O)CCN1CCN(C)CC1
|
| InChi Key |
JUPOTOIJLKDAPF-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C32H36N8O2/c1-22-5-3-6-24(34-22)21-40-27-8-4-7-26(30(27)31(36-40)23-9-10-23)35-32(41)28-20-33-29-19-25(11-12-39(28)29)42-18-17-38-15-13-37(2)14-16-38/h3-8,11-12,19-20,23H,9-10,13-18,21H2,1-2H3,(H,35,41)
|
| Chemical Name |
N-[3-cyclopropyl-1-[(6-methylpyridin-2-yl)methyl]indazol-4-yl]-7-[2-(4-methylpiperazin-1-yl)ethoxy]imidazo[1,2-a]pyridine-3-carboxamide
|
| Synonyms |
c-Fms-IN-12 ARRY-382 ARRY382 c-Fms IN-12
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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 | 1.7709 mL | 8.8546 mL | 17.7091 mL | |
| 5 mM | 0.3542 mL | 1.7709 mL | 3.5418 mL | |
| 10 mM | 0.1771 mL | 0.8855 mL | 1.7709 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.
Link: https://clinicaltrials.gov/ct2/show/NCT02880371
Conditions:Advanced Solid TumorsProducts are for research use only; We do not sell to patients
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