TTT-3002   Click here for help

GtoPdb Ligand ID: 11134

Synonyms: TTT3002
Compound class: Synthetic organic
Comment: TTT-3002 is an experimental indolocarbazole kinase inhibitor. It was originally reported as a LRRK2 inhibitor (including activity against the G2019S and R1441C mutations) [3]. Subsequent analysis revealed that TTT-3002 overcomes activating and drug resistance mutations in FLT3 in acute myeloid leukemia cells [2] and is active against FLT3-associated leukemias in vitro and in vivo [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 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.

✖
Hydrogen bond acceptors 6
Hydrogen bond donors 3
Rotatable bonds 2
Topological polar surface area 103.31
Molecular weight 465.18
XLogP 4.74
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
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.

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/)

✖
Canonical SMILES CNC(=O)[C@@]1(N)C[C@@H]2O[C@@]1(C)n1c3ccccc3c3c1c1n2c2ccccc2c1c1c3CNC1=O
Isomeric SMILES CNC(=O)[C@@]1(N)C[C@@H]2O[C@@]1(C)n1c3ccccc3c3c1c1n2c2ccccc2c1c1c3CNC1=O
InChI InChI=1S/C27H23N5O3/c1-26-27(28,25(34)29-2)11-18(35-26)31-16-9-5-3-7-13(16)20-21-15(12-30-24(21)33)19-14-8-4-6-10-17(14)32(26)23(19)22(20)31/h3-10,18H,11-12,28H2,1-2H3,(H,29,34)(H,30,33)/t18-,26+,27-/m0/s1
InChI Key DCAYZGCTSXLIHO-FYCNXDEQSA-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/)
Bioactivity Comments
The antiproliferative activity of TTT-3002 in cancer cell lines is more potent in FLT3-dependent cells (those with activating mutations or high levels of WT expression and autocrine activation) compared to FLT3-independent cell lines [1].
Selectivity at enzymes
Key to terms and symbols Click column headers to sort
Target Sp. Type Action Value Parameter Concentration range (M) Reference
leucine rich repeat kinase 2 Hs Inhibitor Inhibition 9.1 pIC50 - 3
⤷ pIC50 9.1 (IC50 7x10-10 M) [3]
Description: Measuring inhibition of LRRK2-catalyzed phosphorylation of the specific peptide substrate LRRKtide iv vitro
Selectivity at catalytic receptors
Key to terms and symbols Click column headers to sort
Target Sp. Type Action Value Parameter Concentration range (M) Reference
fms related receptor tyrosine kinase 3 Hs Inhibitor Inhibition 9.1 pIC50 - 1
⤷ pIC50 9.1 (IC50 7.2x10-10 M) [1]
Description: Inhibition of FLT3 phosphorylation in Molm14 human leukemia cells that carry the FLT3/ITD activation mutation