ripretinib   Click here for help

GtoPdb Ligand ID: 9175

Synonyms: DCC-2618 | DCC2618 | Quinlock®
Approved drug
ripretinib is an approved drug (FDA (2020), EMA (2021))
Compound class: Synthetic organic
Comment: Ripretinib (DCC-2618) is an orally bioavailable, potent pan-KIT and PDGFRα kinase inhibitor that was developed by Dicephera Pharmaceuticals. It was designed for the treatment of malignancies that are driven by KIT and/or PDGFRα, for example gastrointestinal stromal tumors, glioblastoma multiforme and systemic mastocytosis. Ripretinib has activity across a broad range of resistance mutations in its target kinases, that emerge in response to imatinib treatment. Ripretinib binds to the 'switch pocket' of KIT, a domain that regulates the enzyme's catalytic conformation. Compounds that act in this way are often referred to as switch control inhibitors [1]. Another example of a switch control inhibitor is avapritinib.
The chemical structure shown here matches that supplied to the WHO for the INN, and this is claimed in patent WO2010051373 [2] as Example 39. Note that some PubChem SIDs are linked to an incorrect structure (as represented in PubChem CID 46208890).

ripretinib 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 3
Rotatable bonds 7
Topological polar surface area 88.05
Molecular weight 509.09
XLogP 5.71
No. Lipinski's rules broken 1

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 CNc1ncc2c(c1)n(CC)c(=O)c(c2)c1cc(NC(=O)Nc2ccccc2)c(cc1Br)F
Isomeric SMILES CNc1ncc2c(c1)n(CC)c(=O)c(c2)c1cc(NC(=O)Nc2ccccc2)c(cc1Br)F
InChI InChI=1S/C24H21BrFN5O2/c1-3-31-21-12-22(27-2)28-13-14(21)9-17(23(31)32)16-10-20(19(26)11-18(16)25)30-24(33)29-15-7-5-4-6-8-15/h4-13H,3H2,1-2H3,(H,27,28)(H2,29,30,33)
InChI Key CEFJVGZHQAGLHS-UHFFFAOYSA-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
The US FDA granted ripretinib (DCC-2618) orphan drug designation (ODD) for gastrointestinal stromal tumours (GIST) in 2014. EMA ODD for the same indication followed in 2017.

Following successful progress through clinical trials in patients with advanced GIST, the FDA authorised use for this indication in May 2020 (based on evidence from clinical trial NCT03353753). This approval permits ripretinib's use in patients who have received ≥3 kinase inhibitor regimens, including imatinib therapy. Click here to link to ClinicalTrials.gov's full list of DCC-2618 studies.