TTI-101   Click here for help

GtoPdb Ligand ID: 12268

Synonyms: C188-9 [2] | TTI 101 | TTI101
Compound class: Synthetic organic
Comment: TTI-101(formerly C188-9) is an orally bioavailable STAT3 transcription factor inhibitor. It blocks the tyrosine residue phosphorylation by Janus kinase (JAK) that mediates STAT3 activation, leading to downregulation of STAT3-mediated gene expression. This mechanism of action is considered as a valid approach for the treatment of inflammation, fibrosis, and a range of cancers [1,3].
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 3
Hydrogen bond donors 3
Rotatable bonds 5
Topological polar surface area 104.24
Molecular weight 471.11
XLogP 6.29
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 COc1ccc(cc1)S(=O)(=O)Nc1cc(c(c2c1cccc2)O)c1c(O)ccc2c1cccc2
Isomeric SMILES COc1ccc(cc1)S(=O)(=O)Nc1cc(c(c2ccccc12)O)c1c(ccc2ccccc12)O
InChI InChI=1S/C27H21NO5S/c1-33-18-11-13-19(14-12-18)34(31,32)28-24-16-23(27(30)22-9-5-4-8-21(22)24)26-20-7-3-2-6-17(20)10-15-25(26)29/h2-16,28-30H,1H3
InChI Key QDCJDYWGYVPBDO-UHFFFAOYSA-N
References
1. Bharadwaj U, Kasembeli MM, Robinson P, Tweardy DJ. (2020)
Targeting Janus Kinases and Signal Transducer and Activator of Transcription 3 to Treat Inflammation, Fibrosis, and Cancer: Rationale, Progress, and Caution.
Pharmacol Rev, 72 (2): 486-526. [PMID:32198236]
2. Brotherton-Pleiss C, Yue P, Zhu Y, Nakamura K, Chen W, Fu W, Kubota C, Chen J, Alonso-Valenteen F, Mikhael S et al.. (2021)
Discovery of Novel Azetidine Amides as Potent Small-Molecule STAT3 Inhibitors.
J Med Chem, 64 (1): 695-710. [PMID:33352047]
3. Jung KH, Yoo W, Stevenson HL, Deshpande D, Shen H, Gagea M, Yoo SY, Wang J, Eckols TK, Bharadwaj U et al.. (2017)
Multifunctional Effects of a Small-Molecule STAT3 Inhibitor on NASH and Hepatocellular Carcinoma in Mice.
Clin Cancer Res, 23 (18): 5537-5546. [PMID:28533225]
4. Xu X, Kasembeli MM, Jiang X, Tweardy BJ, Tweardy DJ. (2009)
Chemical probes that competitively and selectively inhibit Stat3 activation.
PLoS One, 4 (3): e4783. [PMID:19274102]