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FM-381 (FM381) is a potent, specific, covalent reversible inhibitor of JAK3 with anti-inflammatory activity. It inhibits JAK with IC50 of 127 pM for JAK3, and is 410, 2700 and 3600-fold selective over JAK1, JAK2 and TYK2, respectively. FM-381 targets the unique Cys909 at the gatekeeper position +7 in JAK3. FM381 has no relevant effect on the activity of any tested kinases except JAK3 at a concentration of 100 nM. At 500 nM, FM381 moderately inhibits 11 other kinases besides JAK3 with residual activities below 50%. FM-381 is found to be inactive in a selectivity panel of frequently hit BRDs (BRD4, BRPF, CECR, FALZ, TAF1, BRD9).
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Physicochemical Properties
| Molecular Formula |
C24H24N6O2
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| Molecular Weight |
428.49
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| Exact Mass |
428.196
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| CAS # |
2226521-65-7
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| Related CAS # |
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| PubChem CID |
122197584
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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 |
749.8±70.0 °C at 760 mmHg
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| Flash Point |
407.3±35.7 °C
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| Vapour Pressure |
0.0±2.5 mmHg at 25°C
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| Index of Refraction |
1.709
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| LogP |
3.77
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
32
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| Complexity |
785
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| Defined Atom Stereocenter Count |
0
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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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Biological Activity
| ln Vitro |
FM-381 is tested at 100 nM and 500 nM concentrations against a panel of 410 kinases. At 100 nM, FM-381 has no discernible impact on the activity of any of the examined kinases other than JAK3. Eleven additional kinases, including JAK3, are moderately inhibited by FM-381 at 500 nM, with residual activity less than 50%. A selectivity panel of frequently hit BRDs (BRD4, BRPF, CECR, FALZ, TAF1, BRD9) reveals that FM-381 is inactive. Human CD4+ T cells with specific JAK3 signaling inhibition from FM-381. In the dose-dependent BRET experiment, FM-381 exhibits an apparent EC50 of 100 nM. It also inhibits phosphorylation of STAT5 induced by IL2 (JAK3/JAK1 dependent) at 100 nM, but not JAK3 independent IL6 (JAK1/2/TYK dependent) stimulated STAT3 signaling in human CD4+ T cells up to 1 µM[1].
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| ln Vivo |
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| Animal Protocol |
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| References |
[1]. Selective JAK3 Inhibitors with a Covalent Reversible Binding Mode Targeting a New Induced Fit Binding Pocket. Cell Chem Biol. 2016 Nov 17;23(11):1335-1340.
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Solubility Data
| Solubility (In Vitro) |
| DMSO:20 mg/mL (46.7 mM) | | Water:< 1mg/mL | | Ethanol:2 mg/mL (4.6 mM) |
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| Solubility (In Vivo) |
(Please use freshly prepared in vivo formulations for optimal results.)
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| Preparing Stock Solutions |
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1 mg |
5 mg |
10 mg |
| 1 mM |
2.3338 mL |
11.6689 mL |
23.3378 mL |
| 5 mM |
0.4668 mL |
2.3338 mL |
4.6676 mL |
| 10 mM |
0.2334 mL |
1.1669 mL |
2.3338 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. |
