ravoxertinib   Click here for help

GtoPdb Ligand ID: 9229

Synonyms: example 39 [WO2013130976] | GDC-0994
PDB Ligand
Compound class: Synthetic organic
Comment: Ravoxertinib (GDC-0994) is an orally available, small molecule selective inhibitor of extracellular signal-regulated kinase 1/2 (ERK1/2) in early clinical development [1]. It is compound 22 in [1]. ERK1 is formally known as mitogen-activated protein kinase 3 (MAPK3) and ERK2 as mitogen-activated protein kinase 1 (MAPK1). GDC-0994 is example 39 claimed in patent WO2013130976 [2].
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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

ravoxertinib is commercially available from our sponsors

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 Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/). 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 6
Hydrogen bond donors 2
Rotatable bonds 6
Topological polar surface area 97.86
Molecular weight 440.12
XLogP 3.65
No. Lipinski's rules broken 0

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
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.

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)

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Canonical SMILES OCC(n1ccc(cc1=O)c1ccnc(n1)Nc1ccnn1C)c1ccc(c(c1)F)Cl
Isomeric SMILES OC[C@@H](n1ccc(cc1=O)c1ccnc(n1)Nc1ccnn1C)c1ccc(c(c1)F)Cl
InChI InChI=1S/C21H18ClFN6O2/c1-28-19(5-8-25-28)27-21-24-7-4-17(26-21)13-6-9-29(20(31)11-13)18(12-30)14-2-3-15(22)16(23)10-14/h2-11,18,30H,12H2,1H3,(H,24,26,27)/t18-/m1/s1
InChI Key RZUOCXOYPYGSKL-GOSISDBHSA-N

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
No information available.
Summary of Clinical Use Click here for help
GDC-0994 is being evaluated in Phase 1 clinical trials. NCT01875705 is a dose-escalating trial in patients with locally advanced or metastatic solid tumors, and NCT02457793 is assessing GDC-0994 in combination with the MEK 1/2 inhibitor cobimetinib, again in patients with locally advanced or metastatic solid tumors.
Mechanism Of Action and Pharmacodynamic Effects Click here for help
ERK1/2 represent an essential node within the RAS/RAF/MEK/ERK signaling cascade that is commonly activated by oncogenic mutaions in pathway kinases such as RAF and MEK. It is hoped that simultaneous targeting of multiple nodes in the pathway, such as MEK and ERK, will provide enhanced clinical benefit, and may also reduce the incidence of acquired resistance which commonly develops to kinase inhibitors.
Clinical Trials
Clinical Trial ID Title Type Source Comment References
NCT01875705 A Dose-Escalation Study of GDC-0994 in Patients With Locally Advanced or Metastatic Solid Tumors Phase 1 Interventional Genentech, Inc.
NCT02457793 A Study of the Safety, Tolerability, and Effects of Cobimetinib and GDC-0994 in Patients With Locally Advanced or Metastatic Solid Tumors Phase 1 Interventional Genentech, Inc.