CU-115

CU-115 is a potent TLR8 antagonist (IC50=1.04 µM), and shows selective for TLR8 over TLR7 (IC50=>50 µM). CU-115 decreases TNF-α and IL-1β production activated by R-848 in THP-1 cells.

Product information

CAS Number: 2471982-20-2

Molecular Weight: 569.21

Formula: C21H11F7INO2

Chemical Name: N-{4-[3,5-bis(trifluoromethyl)phenoxy]phenyl}-2-fluoro-6-iodobenzamide

Smiles: O=C(NC1C=CC(=CC=1)OC1C=C(C=C(C=1)C(F)(F)F)C(F)(F)F)C1=C(I)C=CC=C1F

InChiKey: QYSLCRYVUJORPX-UHFFFAOYSA-N

InChi: InChI=1S/C21H11F7INO2/c22-16-2-1-3-17(29)18(16)19(31)30-13-4-6-14(7-5-13)32-15-9-11(20(23,24)25)8-12(10-15)21(26,27)28/h1-10H,(H,30,31)

Technical Data

Appearance: Solid Power

Purity: ≥98% (or refer to the Certificate of Analysis)

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥12 months if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined

HS Tariff Code: 382200

How to use

In Vitro:

In endosomal and non-endosomal TLR specificity studies, Human embryonic kidney (HEK) 293 cells expressing human tolllike receptor (hTLR) gene and an inducible secreted embryonic alkaline phosphatase (SEAP) reporter gene were incubated with CU-115 for 16 hours. As a result, CU-115 displays activity for TLR7 and TLR8 at low concentrations (0.5 μM). CU-115 does not modulate the NF-kB inhibition induced by Pam2CSK4, Pam3CSK4, Poly(I:C), LPS, R848, and Flic in HEK-293 TLR1/2, TLR2/6, TLR3, and TLR4 cells. And CU-115 inhibits TLR9 signaling at 1, 5, and 20 µM and ~10-25% inhibition. CU-115 (5-20 µM) inhibits increases in type I IFN transcriptional activity induced by the ssRNA nucleic acid ligands 3p-hpRNA or G3-YSD in a luciferase reporter assay. CU-115 (0.5, 1.0, 5, and 20 µM; 16 hours) is nontoxic at low concentrations (0.5 and 20 μM) and toxic at 100 μM in Hek293 TLR7 and TLR8 cells. CU-115 also is nontoxic at low concentrations (0.5 and 20 μM) and displays partial toxicity at 100 μM in THP Dual cells. The enzyme-linked immunosorbent assay (ELISA) is performed to measure upregulation/inhibition of TNF-α in human THP-1 cells (hTHP-1). CU-115 (5-20 µM) abolishes the TNF-α production activated by R848 (1 µg/ml) in hTHP1. It also represses the expression of IL-1β in hTHP-1 cells. These results suggest that CU-115 suppresses TLR8 and TLR7 signaling pathways.

References:

1. Rosaura Padilla-Salinas, et al. Discovery of Novel Small Molecule Dual Inhibitors Targeting Toll-Like Receptors 7 and 8. J Med Chem. 2019 Nov 27;62(22):10221-10244.

Products are for research use only. Not for human use.