Physicochemical Properties
| Molecular Formula | C26H33N9O3S |
| Molecular Weight | 551.66 |
| Exact Mass | 551.242 |
| CAS # | 1643497-70-4 |
| PubChem CID | 121595975 |
| Appearance | Typically exists as solid at room temperature |
| LogP | 2.8 |
| Hydrogen Bond Donor Count | 2 |
| Hydrogen Bond Acceptor Count | 10 |
| Rotatable Bond Count | 9 |
| Heavy Atom Count | 39 |
| Complexity | 970 |
| Defined Atom Stereocenter Count | 1 |
| SMILES | CC[C@H](C)N1C2=CC(=NC=C2C(=N1)N3CC(C3)C(C)(C)O)NC4=NC(=NC=C4)C5=CN(N=C5)S(=O)(=O)C6CC6 |
| InChi Key | RDWYRIOEHIKPRE-INIZCTEOSA-N |
| InChi Code | InChI=1S/C26H33N9O3S/c1-5-16(2)35-21-10-23(28-12-20(21)25(32-35)33-14-18(15-33)26(3,4)36)30-22-8-9-27-24(31-22)17-11-29-34(13-17)39(37,38)19-6-7-19/h8-13,16,18-19,36H,5-7,14-15H2,1-4H3,(H,27,28,30,31)/t16-/m0/s1 |
| Chemical Name | 2-[1-[1-[(2S)-butan-2-yl]-6-[[2-(1-cyclopropylsulfonylpyrazol-4-yl)pyrimidin-4-yl]amino]pyrazolo[4,3-c]pyridin-3-yl]azetidin-3-yl]propan-2-ol |
| 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 | EGFR-IN-2 (Compound 21) activates the mutant del<746-750 cell line PC9 and the wild-type cell line H292. It also inhibits EGFR autophosphorylation in the double mutant TMLR cell line H1975 and the double mutant TMdel cell line PC9-ER, with IC50 values of 0.027 μM, 0.009 μM, 0.033 μM, and 0.218 μM, respectively. Furthermore, EGFR-IN-2 demonstrated strong antiproliferative effects on the single activating mutant PC9 cell line (IC50=0.151 μM) and the T790M mutant-carrying H1975 cell line (IC50=0.361 μM). Furthermore, when assessed in the 225 kinase panel, EGFR-IN-2 also demonstrated good selectivity towards other kinases (>70% inhibition of 12/225 kinases when tested at 0.1 μM, 61-fold higher than the TMLR Ki, 63 times TMLR Ki) TMdel Ki) [1]. |
| ln Vivo | In the mouse H1975 (TMLR) xenograft model, EGFR-IN-2 (compound 21) was investigated to investigate its inhibitory effect on pEGFR levels in vivo. Following an oral dosage of 21 50 mg/kg, free plasma concentrations of EGFR-IN-2 were sustained for 8 hours, and they either matched or surpassed the 0.027 μM in vitro p-EGFR IC50. The p-EGFR IC50 coverage was increased to 16 hours postdose when administered at a dose of 100 mg/kg. At these time points, corresponding knockdown of p-EGFR and downstream effectors pERK1/2 and AKT levels was seen, indicating in vivo target involvement. Following intravenous and oral administration, EGFR-IN-2 in mice exhibited a plasma clearance of 104 mL/kg/min and a bioavailability of 19%. Dogs have a 30% oral bioavailability and a plasma clearance of 13 mL/kg per minute [1]. |
| References |
[1]. Discovery of a Noncovalent, Mutant-Selective Epidermal Growth Factor Receptor Inhibitor. J Med Chem. 2016 Oct 13;59(19):9080-9093. |
Solubility Data
| 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 |
| 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 | 1.8127 mL | 9.0636 mL | 18.1271 mL | |
| 5 mM | 0.3625 mL | 1.8127 mL | 3.6254 mL | |
| 10 mM | 0.1813 mL | 0.9064 mL | 1.8127 mL |