FM-381 HCl is a Chemical Probe For JAK3 and JAK3 specific reversible covalent inhibitor. It has strong isoform and kinome selectivity. FM-381 showed sufficient stability for in vivo application.
Physicochemical Properties
| Molecular Formula | C24H24N6O2 |
| Molecular Weight | 428.486364364624 |
| Exact Mass | 428.196 |
| CAS # | 2226521-65-7 |
| PubChem CID | 122197584 |
| Appearance | Light yellow to yellow solid powder |
| Density | 1.4±0.1 g/cm3 |
| Boiling Point | 749.8±70.0 °C at 760 mmHg |
| Flash Point | 407.3±35.7 °C |
| Vapour Pressure | 0.0±2.5 mmHg at 25°C |
| Index of Refraction | 1.709 |
| LogP | 3.77 |
| Hydrogen Bond Donor Count | 1 |
| Hydrogen Bond Acceptor Count | 5 |
| Rotatable Bond Count | 4 |
| Heavy Atom Count | 32 |
| Complexity | 785 |
| Defined Atom Stereocenter Count | 0 |
| SMILES | CN(C)C(=O)/C(=C/C1=CC=C(O1)C2=NC3=CN=C4C(=C3N2C5CCCCC5)C=CN4)/C#N |
| InChi Key | GJMZWYLOARVASY-NTCAYCPXSA-N |
| InChi Code | InChI=1S/C24H24N6O2/c1-29(2)24(31)15(13-25)12-17-8-9-20(32-17)23-28-19-14-27-22-18(10-11-26-22)21(19)30(23)16-6-4-3-5-7-16/h8-12,14,16H,3-7H2,1-2H3,(H,26,27)/b15-12+ |
| Chemical Name | (E)-2-cyano-3-[5-(3-cyclohexyl-3,5,8,10-tetrazatricyclo[7.3.0.02,6]dodeca-1,4,6,8,11-pentaen-4-yl)furan-2-yl]-N,N-dimethylprop-2-enamide |
| HS Tariff Code | 2934.99.9001 |
| 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) |
Biological Activity
| ln Vitro | FM-381 was evaluated against a panel of 410 kinases at doses of 100 nM and 500 nM. FM-381 had no relevant effect on the activity of any of the tested kinases except JAK3 at 100 nM. At a dose of 500 nM, FM-381 moderately inhibits 11 other kinases except JAK3, with residual activity below 50%. FM-381 was reported to be inactive in a chosen panel of frequently attacked BRDs (BRD4, BRPF, CECR, FALZ, TAF1, BRD9). FM-381 specifically suppresses JAK3 signaling in human CD4+ T cells. FM-381 has an apparent EC50 of 100 nM in a dose-dependent BRET test and blocks IL2-stimulated (JAK3/JAK1-dependent) STAT5 phosphorylation at 100 nM but not JAK3-independent STAT5 phosphorylation in humans IL6 (JAK1/2/TYK dependent) promotes STAT3 signaling in CD4+ T cells up to 1 µM [1]. |
| 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. |
Solubility Data
| Solubility (In Vitro) | DMSO : ~8.33 mg/mL (~19.44 mM) |
| 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 (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *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). 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)] *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. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL 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). Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 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 |