Home MAPK ERK inhibitor MK-8353 (SCH900353) For research use only.

MK-8353 (SCH900353)

MK-8353 (SCH900353) is an orally bioavailable, selective, and potent ERK inhibitor that inhibits activated ERK1 and ERK2 in vitro, with IC50 values of 23.0 nM and 8.8 nM, respectively (IMAP kinase assay), and nonactivated ERK2, with an IC50 of 0.5 nM (MEK1-ERK2-coupled assay).

MK-8353 (SCH900353) Chemical Structure

MK-8353 (SCH900353) Chemical Structure

CAS No. 1184173-73-6

Purity & Quality Control

Batch: S870101 DMSO]50 mg/mL]false]Water]Insoluble]false]Ethanol]Insoluble]false Purity: 99.92%
99.92

MK-8353 (SCH900353) Related Products

Signaling Pathway

ERK Signaling Pathways

ERK Signaling Pathway

Biological Activity

Description MK-8353 (SCH900353) is an orally bioavailable, selective, and potent ERK inhibitor that inhibits activated ERK1 and ERK2 in vitro, with IC50 values of 23.0 nM and 8.8 nM, respectively (IMAP kinase assay), and nonactivated ERK2, with an IC50 of 0.5 nM (MEK1-ERK2-coupled assay).
Targets
ERK2 [1]
(Cell-free assay)		 ERK1 [1]
(Cell-free assay)
7 nM 20 nM
In vitro
In vitro

MK-8353 is a potent and selective inhibitor of both active and inactive ERK1 and ERK2 kinases (IC50=20 and 7 nM, respectively). MK-8353 is not a potent inhibitor of human CYPs 1A2, 2C9, 2C19 or 2D6 but inhibits CYP 3A4 (pre-incubation) in vitro and shows inhibition of CYP 3A4 and 2C8 (IC50 = 1.7 & 3.5 μM), which can cause drug-drug interactions when co administered with drugs that are primarily metabolized by CYP 2C8 or 3A4. MK-8353 is a weak inhibitor of hERG current, producing 16% inhibition at 0.6 μM. The IC50 values for inhibiting cell prolifertion are 371, 51, and 23 nM in A2058, HT-29, and Colo-205 cells respectively. In addition to inhibiting the kinase activity of ERK, MK-8353 prevents the phosphorylation of ERK by MEK[1]. MK-8353 demonstrates kinase selectivity over a 227-human kinase panel; no additional kinase in the panel is inhibited by more than 35% at the 0.1 μM concentration, and only 3 kinases (CLK2, FLT4, and Aurora B) are inhibited >50% at the 1.0 μM concentration[2].
Cell Research Cell lines A2058 cells
Concentrations 0, 3, 10, 30, 100, 300 nM
Incubation Time 24 hours
Method

A2058 cells (1 × 106 cells per 10-cm dish) were treated with increasing concentrations of MK-8353 (nM) for 24 hours. Whole cell lysates were subjected to immunoblot analysis.
Experimental Result Images Methods Biomarkers Images PMID
Western blot pERK / ERK / pRSK / RSK pERK / ERK / pRSK / RSK 29467321
In Vivo
In vivo

The in vivo pharmacokinetics and metabolism of MK-8353 are evaluated in male CD1 mice, Sprague Dawley (SD) rats, guinea pigs, beagle dogs, and cynomologus monkeys. With the exception of monkeys, MK-8353 shows moderate clearance after IV administration in all species, with a half-life range of 1.3-2.8 hr and a mean residence time range of 1.5-4.0 hr. Acceptable oral bioavailability is seen in mice, rats and dogs (23-80%) but low oral bioavailability in monkeys (2%). The permeability observed in Caco-2 cells was high (135 nm/sec), suggesting that intestinal absorption and permeability in humans should also be high. The steady-state volume of distribution in mice, dogs and monkeys are in the range of 0.9-3.3 L/kg, while in rats it is 0.1 L/kg. MK-8353 displays anti-tumor efficacy in several BRAF-mutant models[1].
Animal Research Animal Models Female athymic nude mice (inoculated with Colo-205 cancer cells) or SCID mice (inoculated with SK-MEL-28 melanoma cells)
Dosages 30, 45 and 60 mg/kg
Administration p.o.
NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT03745989 Completed
Solid Tumors
Merck Sharp & Dohme LLC
 February 22 2019 Phase 1

Chemical Information & Solubility

Molecular Weight 691.84 Formula

C37H41N9O3S
CAS No. 1184173-73-6 SDF --
Smiles CC(C)OC1=NC=C(C=C1)C2=NNC3=C2C=C(C=C3)NC(=O)C4(CCN(C4)CC(=O)N5CCC(=CC5)C6=CC=C(C=C6)C7=NN(C=N7)C)SC
Storage (From the date of receipt) 3 years -20°C powder

In vitro
Batch:

DMSO : 50 mg/mL ( (72.27 mM) Moisture-absorbing DMSO reduces solubility. Please use fresh DMSO.)

Water : Insoluble

Ethanol : Insoluble


Molecular Weight Calculator

In vivo
Batch:

Add solvents to the product individually and in order.


In vivo Formulation Calculator

Preparing Stock Solutions

Molarity Calculator

Mass Concentration Volume Molecular Weight

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)

mg/kg g μL

Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)

% DMSO % % Tween 80 % ddH2O
%DMSO %

Calculation results:

Working concentration: mg/ml;

Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid 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 master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such
as vortex, ultrasound or hot water bath can be used to aid dissolving.

Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

Tel: +1-832-582-8158 Ext:3
If you have any other enquiries, please leave a message.

* Indicates a Required Field

Please enter your name.
Please enter your email. Please enter a valid email address.
Please write something to us.
Tags: buy MK-8353 (SCH900353) | MK-8353 (SCH900353) supplier | purchase MK-8353 (SCH900353) | MK-8353 (SCH900353) cost | MK-8353 (SCH900353) manufacturer | order MK-8353 (SCH900353) | MK-8353 (SCH900353) distributor