MK-8353   Click here for help

GtoPdb Ligand ID: 9974

Synonyms: MK8353 | SCH900353
PDB Ligand
Compound class: Synthetic organic
Comment: MK-8353 (formerly know as SCH900353) is an orally bioavailable dual mechanism ERK1/2 inhibitor, i.e. it inhibits ERK1/2 catalytic activity and phosphorylation of ERK1/2 [1]. It has improved pharmacokinetic properties in comparison to SCH772984 (a preclinical ERK1/2 inhibtor tool compound) and has shown preliminary anti-tumour efficacy in patients with BRAF or RAS mutated metastatic melanoma and colorectal cancers.
(Note: ERK1= MAPK3, ERK2= MAPK1).
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Ligand Activity Visualisation Charts

These are box plot that provide a unique visualisation, summarising all the activity data for a ligand taken from ChEMBL and GtoPdb across multiple targets and species. Click on a plot to see the median, interquartile range, low and high data points. A value of zero indicates that no data are available. A separate chart is created for each target, and where possible the algorithm tries to merge ChEMBL and GtoPdb targets by matching them on name and UniProt accession, for each available species. However, please note that inconsistency in naming of targets may lead to data for the same target being reported across multiple charts.

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View interactive charts of activity data across species
2D Structure
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2D Structure

An image of the ligand's 2D structure. For small molecules with SMILES these are drawn using the NCI/CADD Chemical Identifier Resolver. Click on the image to access the chemical structure search tool with the ligand pre-loaded in the structure editor. For other types of ligands, e.g. longer nucleotides and peptides, a manually drawn representation of the molecule may be provided.

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Physico-chemical Properties
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Physico-chemical Properties

Calculated molecular properties are available for small molecules and natural products (not peptides). Properties were generated using the CDK toolkit. All properties were selected to enable the prediction of the Lipinski Rule-of-Five profile or ‘druglikeness’ for each ligand. For more info on each category see the help pages.

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Hydrogen bond acceptors 9
Hydrogen bond donors 2
Rotatable bonds 12
Topological polar surface area 159.46
Molecular weight 691.31
XLogP 5.1
No. Lipinski's rules broken 1
SMILES / InChI / InChIKey
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SMILES / InChI / InChIKey

SMILES (Simplified Molecular Input Line Entry Specification) A specification for unambiguously describing the structure of chemical molecules using short ASCII strings. Canonical SMILES specify a unique representation of the 2D structure without chiral or isotopic specifications. Isomeric SMILES include chiral specification and isotopes.

Standard InChI (IUPAC International Chemical Identifier) and InChIKey InChI is a non-proprietary, standard, textual identifier for chemical substances designed to facilitate linking of information and database searching. An InChIKey is a simplified version of a full InChI, designed for easier web searching.

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Canonical SMILES CSC1(CCN(C1)CC(=O)N1CCC(=CC1)c1ccc(cc1)c1ncn(n1)C)C(=O)Nc1ccc2c(c1)c(n[nH]2)c1ccc(nc1)OC(C)C
Isomeric SMILES CS[C@]1(CCN(C1)CC(=O)N1CCC(=CC1)c1ccc(cc1)c1ncn(n1)C)C(=O)Nc1ccc2c(c1)c(n[nH]2)c1ccc(nc1)OC(C)C
InChI InChI=1S/C37H41N9O3S/c1-24(2)49-32-12-9-28(20-38-32)34-30-19-29(10-11-31(30)41-42-34)40-36(48)37(50-4)15-18-45(22-37)21-33(47)46-16-13-26(14-17-46)25-5-7-27(8-6-25)35-39-23-44(3)43-35/h5-13,19-20,23-24H,14-18,21-22H2,1-4H3,(H,40,48)(H,41,42)/t37-/m0/s1
InChI Key KPQQGHGDBBJGFA-QNGWXLTQSA-N
No information available.
Summary of Clinical Use Click here for help
A Phase 1 study of MK-8353 as a single agent in patients with advanced solid tumours (NCT01358331) was terminated; results from this trial were published by MOschos et al. (2018) [1]. ClinicalTrials.gov has trial number NCT01358331 listed as 'recruiting', and this study is designed to evaluate the eficacy of MK-8353 in combination with the approved PD-1 checkpoint inhibitor pembrolizumab, in patients with advanced colorectal cancer.
Clinical Trials
Clinical Trial ID Title Type Source Comment References
NCT01358331 A Study of the Safety, Tolerability, and Efficacy of MK-8353 in Participants With Advanced Solid Tumors (MK-8353-001) Phase 1 Interventional Merck Sharp & Dohme Corp.
NCT02972034 Study of MK-8353 in Combination With Pembrolizumab (MK-3475) in Participants With Advanced Malignancies (MK-8353-013) Phase 1 Interventional Merck Sharp & Dohme Corp.