Physicochemical Properties
| CAS # | 2494010-42-1 |
| Appearance | Off-white to light yellow solid powder |
| 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
| Targets | ERK1 2.8 nM (IC50) ERK2 5.9 nM (IC50) |
| ln Vitro | SHR2415 possesses inhibitory activity for ERK1 and ERK2 with IC50 values of 2.8 nM and 5.9 nM, respectively[1]. SHR2415 exhibits the cellular potency with an IC50 value of 44.6 nM in Colo205 cells[1]. |
| ln Vivo | SHR2415 (iv; 1 mg/kg for mouse and rat; po; 2 mg/kg for mouse, rat, and dog) exhibits a decent in vivo exposure and a good PK profile across species[1]. SHR2415 (25, 50 mg/kg; po; once daily, for 14 days) exhibits strong in vivo effectiveness in a mouse Colo205 xenograft model along with acceptable PK profiles across species[1]. |
| Animal Protocol |
Animal/Disease Models: Mouse, Rat and Dog[1] Doses: 1 mg/kg (mouse and rat), 0.5 mg/kg (dog), 2 mg/kg (mouse, rat, and dog) Route of Administration: iv (mouse and rat) and po (mouse, rat, and dog) Experimental Results: Species Mouse Rat Dog Cmax(ng/mL) 604 219 526 AUC0-tp.o. (ng/mL·h) 2460 726 3271 t1/2p.o. (h) 3.5 2.1 3.2 CL(mL/min/kg ) 12.2 25.3 10.5 F (%) 90.8 45.8 101. Animal/Disease Models: Balb/c mouse Colo205 tumor xenograft model[1] Doses: 25, 50 mg/kg Route of Administration: po; one time/day, for 14 days Experimental Results: Cpds ID @ Dose Plasma Tumor AUC-tumor/AUC-plasma TGI(%) Cmax (ng/mL) AUC (h*ng/mL) Cmax (ng/mL) AUC (h*ng/mL) SHR2415@25 mg/kg 5147 21364 9460 30260 1.42 112 |
| References |
[1]. Discovery of SHR2415, a Novel Pyrrole-Fused Urea Scaffold ERK1/2 Inhibitor. ACS Med Chem Lett. 2022 Apr 1;13(4):701-706. |
Solubility Data
| Solubility (In Vitro) | DMSO: 100 mg/mL (215.55 mM) |
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.39 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 25.0 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: ≥ 2.5 mg/mL (5.39 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 25.0 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: ≥ 2.5 mg/mL (5.39 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 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |