STC-15   Click here for help

GtoPdb Ligand ID: 12894

Synonyms: Example 2 [WO2021111124A1] | STC15
Compound class: Synthetic organic
Comment: STC-15 is an oral small molecule inhibitor of the the RNA methyltransferase METTL3. METTL3 'writes' N6-methyladenosine (m6A) modifications on mRNA and long non-coding RNA (lncRNA) targets, and these modifications regulate the stability, splicing, transport and translation of the m6A RNAs. METTL3‑mediated methylation has been implicated in the potentiation of tumour growth, cell invasion and metastasis. Inhibition of METTL3 function is proposed to induce anti-cancer immunity and reduce cancer growth [2-3].
The structure of STC-15 was disclosed at the American Chemical Society (ACS) meeting in August 2023. It is one of the compounds claimed in Storm Therapeutics' patent WO2021111124A1 [1].
Click here for help

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.

✖

View interactive charts of activity data across species
2D Structure
Click here for help

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.

✖
Click here for structure editor
Physico-chemical Properties
Click here for help

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.

✖
Hydrogen bond acceptors 7
Hydrogen bond donors 3
Rotatable bonds 8
Topological polar surface area 85.83
Molecular weight 415.49
XLogP 1
No. Lipinski's rules broken 0
SMILES / InChI / InChIKey
Click here for help

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.

✖
Canonical SMILES C1=CC2=NC(=CC(=O)N2C=C1)C(=O)NCC3=CC4=C(C=C3)C=C(CNCC5CCC5)N4
Isomeric SMILES O=C(NCC1=CC2=C(C=C(CNCC3CCC3)N2)C=C1)C4=CC(=O)N5C=CC=CC5=N4
InChI InChI=1S/C24H25N5O2/c30-23-12-21(28-22-6-1-2-9-29(22)23)24(31)26-14-17-7-8-18-11-19(27-20(18)10-17)15-25-13-16-4-3-5-16/h1-2,6-12,16,25,27H,3-5,13-15H2,(H,26,31)
InChI Key MFQFZLWCFZZHAI-UHFFFAOYSA-N
References
1. Blackaby WP, Hardick DJ, Thomas EJ, Brookfield FA, Shepherd J, Bubert C, Ridgill MP. (2021)
Polyheterocyclic compounds as mettl3 inhibitors.
Patent number: WO2021111124A1. Assignee: Storm Therapeutics Limited. Priority date: 01/12/2020. Publication date: 10/06/2021.
2. Guirguis AA, Ofir-Rosenfeld Y, Knezevic K, Blackaby W, Hardick D, Chan YC, Motazedian A, Gillespie A, Vassiliadis D, Lam EYN et al.. (2023)
Inhibition of METTL3 Results in a Cell-Intrinsic Interferon Response That Enhances Antitumor Immunity.
Cancer Discov, 13 (10): 2228-2247. [PMID:37548590]
3. Pan Y, Chen H, Zhang X, Liu W, Ding Y, Huang D, Zhai J, Wei W, Wen J, Chen D et al.. (2023)
METTL3 drives NAFLD-related hepatocellular carcinoma and is a therapeutic target for boosting immunotherapy.
Cell Rep Med, 4 (8): 101144. [PMID:37586322]