| Size | Price | Stock | Qty |
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| 2mg |
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| 5mg |
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| 10mg |
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| 25mg |
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| Other Sizes |
Purity: ≥98%
| Targets |
p38α (p38 mitogen-activated protein kinase). [1]
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| ln Vitro |
ARRY-797 reduced phosphorylated p38α in heart tissue homogenates from treated LmnaH222P/H222P mice compared to placebo, as shown by immunoblotting. It did not reduce phosphorylation of ERK1/2, indicating selectivity for p38α. [1]
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| ln Vivo |
Oral administration of ARRY-797 (30 mg/kg twice daily for 4 weeks) to 16-week-old LmnaH222P/H222P mice significantly prevented left ventricular dilatation and deterioration of fractional shortening. Echocardiography showed that treated mice had significantly smaller left ventricular end-diastolic diameter (LVEDD: 4.0 ± 0.1 mm vs. placebo 4.6 ± 0.1 mm, P<0.005), smaller left ventricular end-systolic diameter (LVESD: 3.0 ± 0.2 mm vs. placebo 3.9 ± 0.1 mm, P<0.05), and increased fractional shortening (FS: 25.0 ± 2.7% vs. placebo 14.6 ± 1.3%, P<0.005). [1]
ARRY-797 treatment also significantly reduced the expression of mRNAs encoding sarcomere-related proteins (Mlc-1a and Acta2) and natriuretic peptides (Nppa and NppB) in hearts of LmnaH222P/H222P mice, but did not reduce expression of collagen genes Col1a1 and Col1a2 involved in cardiac fibrosis. [1] |
| Cell Assay |
Cardiomyocyte isolation: Ventricular cardiomyocytes were isolated from 16-week-old LmnaH222P/H222P and wild-type mice. Hearts were removed, aorta cannulated, and perfused with Ca2+-free buffer followed by collagenase I/II solution. Left ventricular tissue was teased apart and individual cells released by pipetting. Ca2+ concentration was gradually increased to 500 μM. Protein extracts from isolated cardiomyocytes were then used for immunoblotting to detect phosphorylated p38α. [1]
Immunoblotting: Protein extracts from heart tissue or isolated cardiomyocytes were separated by SDS-PAGE, transferred to nitrocellulose membranes, and blotted with primary antibodies against p38α, phosphorylated p38α, MKK6, phosphorylated MKK6, ERK1/2, and phosphorylated ERK1/2. Secondary antibodies were horseradish peroxidase-conjugated, and recognized proteins were visualized by enhanced chemiluminescence. [1] |
| Animal Protocol |
Mouse treatment: Male LmnaH222P/H222P mice (16 weeks of age) were treated with ARRY-797 (ARRY-371797) at a dose of 30 mg/kg twice daily by oral gavage for 4 weeks. The compound was dissolved in Water for Injection (WFI) at a concentration of 0.5 mg/mL. Placebo control received the same volume of WFI. Treatment continued until 20 weeks of age, after which mice were analyzed by echocardiography and then sacrificed for biochemical studies. [1]
Echocardiography: Mice were anesthetized with 1.5% isoflurane in O2 and placed on a heating pad. A 30 MHz transducer was applied to the chest wall. Cardiac ventricular dimensions and fractional shortening were measured in 2D mode and M-mode. [1] |
| Toxicity/Toxicokinetics |
ARRY-797 is a highly selective, potent p38α inhibitor that was under investigation in a Phase II clinical trial for acute inflammatory pain at the time of the study. In the LmnaH222P/H222P mouse model of dilated cardiomyopathy caused by lamin A/C mutation, it prevented left ventricular dilatation and deterioration of cardiac function but did not reduce fibrosis. The study suggests that p38α inhibition may be a potential therapeutic strategy for LMNA cardiomyopathy. [1]
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| References |
Hum Mol Genet.2012 Oct 1;21(19):4325-33.
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| Molecular Formula |
C22H26F2N4O2
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| Molecular Weight |
416.47
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| Exact Mass |
416.202
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| CAS # |
1036404-17-7
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| Related CAS # |
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| PubChem CID |
46883775
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| Appearance |
Typically exists as solid at room temperature
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| LogP |
3.9
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
8
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| Heavy Atom Count |
30
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| Complexity |
565
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CC(C)CN1C2=CC(=C(C=C2C=N1)OC3=C(C=C(C=C3)F)F)C(=O)NCCN(C)C
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| InChi Key |
IFGWYHGYNVGVRB-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C22H26F2N4O2/c1-14(2)13-28-19-11-17(22(29)25-7-8-27(3)4)21(9-15(19)12-26-28)30-20-6-5-16(23)10-18(20)24/h5-6,9-12,14H,7-8,13H2,1-4H3,(H,25,29)
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| Chemical Name |
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| Synonyms |
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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 |
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| 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) |
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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 | 2.4011 mL | 12.0057 mL | 24.0113 mL | |
| 5 mM | 0.4802 mL | 2.4011 mL | 4.8023 mL | |
| 10 mM | 0.2401 mL | 1.2006 mL | 2.4011 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.
ARRY-371797prevents LV dilatation and deterioration of FS inLmnaH222P/H222Pmice. (A) Schematic representation of the treatment protocol ofLmnaH222P/H222Pmice withARRY-371797.Hum Mol Genet.2012 Oct 1;21(19):4325-33. |
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ARRY-371797decreases expression of genes encoding proteins involved in sarcomere organization and natriuretic peptides but not collagens inLmnaH222P/ H222Pmice.Hum Mol Genet.2012 Oct 1;21(19):4325-33. |
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