SHP836 (SHP-836) is a novel, potent, and allosteric inhibitor SHP2 with anticancer activity. It inhibits SHP2 an IC50 of 12 μM for the full length SHP2.
Physicochemical Properties
| Molecular Formula | C16H19CL2N5 |
| Molecular Weight | 352.261560678482 |
| Exact Mass | 351.101 |
| CAS # | 1957276-35-5 |
| PubChem CID | 76966642 |
| Appearance | Light green to green solid powder |
| LogP | 3.4 |
| Hydrogen Bond Donor Count | 2 |
| Hydrogen Bond Acceptor Count | 5 |
| Rotatable Bond Count | 2 |
| Heavy Atom Count | 23 |
| Complexity | 389 |
| Defined Atom Stereocenter Count | 2 |
| SMILES | ClC1C(=CC=CC=1C1C=NC(=NC=1N)N1C[C@@H](C)N[C@@H](C)C1)Cl |
| InChi Key | SKFRRNOLFFQBQU-AOOOYVTPSA-N |
| InChi Code | InChI=1S/C16H19Cl2N5/c1-9-7-23(8-10(2)21-9)16-20-6-12(15(19)22-16)11-4-3-5-13(17)14(11)18/h3-6,9-10,21H,7-8H2,1-2H3,(H2,19,20,22)/t9-,10+ |
| Chemical Name | 5-(2,3-dichlorophenyl)-2-[(3S,5R)-3,5-dimethylpiperazin-1-yl]pyrimidin-4-amine |
| 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 | SHP836 maintains SHP2's active conformation, which prevents the catalytic site from accessing the substrate and blocks it [1]. |
| References |
[1]. Structure based design of selective SHP2 inhibitors by De novo design, synthesis and biological evaluation. J Comput Aided Mol Des. 2019 Aug;33(8):759-774. [2]. Allosteric Inhibition of SHP2: Identification of a Potent, Selective, and Orally Efficacious Phosphatase Inhibitor. J Med Chem. 2016 Sep 8;59(17):7773-82. |
Solubility Data
| Solubility (In Vitro) | DMSO : ~250 mg/mL (~709.70 mM) |
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 6.25 mg/mL (17.74 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 62.5 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 6.25 mg/mL (17.74 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 62.5 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. 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. Solubility in Formulation 3: ≥ 6.25 mg/mL (17.74 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 62.5 mg/mL clear DMSO stock solution to 900 μL corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.8388 mL | 14.1941 mL | 28.3881 mL | |
| 5 mM | 0.5678 mL | 2.8388 mL | 5.6776 mL | |
| 10 mM | 0.2839 mL | 1.4194 mL | 2.8388 mL |