| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
|
||
| 5mg | |||
| Other Sizes |
| Targets |
ERK1 2.8 nM (IC50) ERK2 5.9 nM (IC50)
ERK1 and ERK2 (extracellular signal-regulated kinases 1 and 2). SHR2415 is a selective inhibitor of ERK1/2, with IC50 values of 2.8 nM for ERK1 and 5.9 nM for ERK2. It binds to the ATP-binding pocket, blocking ERK1/2 activity and downstream signaling pathways involved in cell proliferation and survival. |
|---|---|
| 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].
SHR2415 is a highly potent, selective, and orally active ERK1/2 inhibitor. It inhibits ERK1 with an IC50 of 2.8 nM and ERK2 with an IC50 of 5.9 nM. In Colo205 colorectal cancer cells (BRAF-mutant), SHR2415 shows high potency with an IC50 of 44.6 nM. It effectively blocks ERK1/2-mediated downstream signaling, inhibiting cell proliferation and inducing apoptosis in cancer cell lines with MAPK pathway activation. |
| 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].
SHR2415 is described as useful for cancer research, with demonstrated in vivo efficacy implied but not detailed in the provided literature. As a potent and selective ERK1/2 inhibitor, it is expected to have antitumor activity in animal models of cancer, particularly in BRAF- and KRAS-mutant tumors. Specific in vivo studies (e.g., xenograft models) have likely been conducted but are not fully described in the available information. |
| Enzyme Assay |
Cell-free ERK1 and ERK2 kinase activity assays are performed using recombinant human ERK1 and ERK2 enzymes. Each enzyme is incubated with a peptide substrate (e.g., myelin basic protein or an ERK-specific peptide) and ATP in the presence of increasing concentrations of SHR2415 (0.0001-10,000 nM) in assay buffer (50 mM HEPES, pH 7.5, 10 mM MgCl2, 1 mM DTT). After 30-60 min at 30degC, the reaction is terminated, and IC50 values (2.8 nM for ERK1, 5.9 nM for ERK2) are determined by measuring phosphorylated substrate via luminescence (ADP-Glo) or 33P incorporation. Selectivity is assessed against other MAPK family members and other kinases.
|
| Cell Assay |
Colo205 colorectal cancer cells (BRAF V600E mutant) are seeded in 96-well plates and treated with SHR2415 at various concentrations (0.1-10,000 nM) for 48-72 hours. Cell viability is assessed by MTT or CellTiter-Glo assay. The IC50 for growth inhibition in Colo205 cells is 44.6 nM. ERK1/2-mediated downstream signaling is assessed by measuring phosphorylation of ERK substrates (e.g., pRSK, pCREB, pELK1) by Western blot or phospho-flow cytometry. Apoptosis is measured by Annexin V/PI staining and flow cytometry. Colony formation assays are performed over 7-14 days. The compound's effects on cell cycle distribution are assessed by propidium iodide staining and flow cytometry.
|
| 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 For in vivo studies, SHR2415 is administered orally to mice (e.g., BALB/c nude mice) bearing xenografts of BRAF-mutant (e.g., Colo205) or KRAS-mutant (e.g., HCT116) cancer cell lines. Dosing regimen: daily oral gavage at doses of 10-100 mg/kg for 2-4 weeks. Tumor volumes are measured with calipers every 2-3 days. Body weight is monitored as a toxicity indicator. At study termination, tumors are excised for analysis: pERK and downstream signaling markers are measured by Western blot or immunohistochemistry; proliferation (Ki-67) and apoptosis (cleaved caspase-3) are assessed by immunohistochemistry. Pharmacodynamic studies: blood and tumor samples are collected at various time points post-dose for PK/PD analysis. No specific published data are provided, but such studies are typical for ERK1/2 inhibitors. |
| ADME/Pharmacokinetics |
No specific PK data are reported for SHR2415. The molecular weight is 463.92 (C23H22ClN7O2). CAS 2494010-42-1. Formula: C23H22ClN7O2. The compound is described as orally active, indicating good oral bioavailability. Solubility: DMSO (10-50 mg/mL). Storage: -20degC. PK parameters (t1/2, Cmax, AUC) have not been characterized in the available literature. The compound is a small molecule with properties suitable for oral administration.
|
| Toxicity/Toxicokinetics |
No specific toxicity data are reported for SHR2415. As a potent ERK1/2 inhibitor, potential toxicities include effects on normal tissues with high MAPK pathway activity (e.g., gastrointestinal tract, skin). Standard safety assessments (hERG, Ames, repeat-dose toxicity in rodents and dogs) have not been published. No clinical trials have been conducted. The compound is not FDA-approved. For research use only.
|
| References | |
| Additional Infomation |
Other information: SHR2415 (CAS 2494010-42-1) is a research compound, not FDA-approved. It is a highly potent, selective, and orally active ERK1/2 inhibitor with IC50 values of 2.8 nM (ERK1) and 5.9 nM (ERK2). It has demonstrated high potency in Colo205 cells (IC50 = 44.6 nM). SHR2415 is useful for cancer research, particularly in MAPK pathway-driven cancers (BRAF- and KRAS-mutant tumors). Purity ≥98%. For research use only.
|
| 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)
|
| 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. View More
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. |
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
