CU-115 is a disabling TLR8 antagonist (IC50=1.04 µM) and shows activity against TLR8 and TLR7 (IC50=>50 µM). The decrease in CU-115 is caused by R-848-activated TNF-α and IL-1β production in THP-1 cells.

Physicochemical Properties

Molecular Formula	C21H11F7INO2
Molecular Weight	569.211
Exact Mass	568.972
CAS #	2471982-20-2
PubChem CID	154734323
Appearance	White to off-white solid powder
Density	1.7±0.1 g/cm3
Boiling Point	427.3±45.0 °C at 760 mmHg
Flash Point	212.2±28.7 °C
Vapour Pressure	0.0±1.0 mmHg at 25°C
Index of Refraction	1.577
LogP	5.16
Hydrogen Bond Donor Count	1
Hydrogen Bond Acceptor Count	9
Rotatable Bond Count	4
Heavy Atom Count	32
Complexity	615
Defined Atom Stereocenter Count	0
InChi Key	QYSLCRYVUJORPX-UHFFFAOYSA-N
InChi Code	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)
Chemical Name	N-[4-[3,5-bis(trifluoromethyl)phenoxy]phenyl]-2-fluoro-6-iodobenzamide
HS Tariff Code	2934.99.9001
Storage	Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Shipping Condition	Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Biological Activity

ln Vitro

Human embryonic kidney (HEK) 293 cells expressing human Toll-like receptor (hTLR) genes and inducible secretory embryonic alkaline phosphatase (SEAP) reporter genes were compared with CU -115 combined for 16 hours in endosomal and non-endosomal TLR specificity experiments. Therefore, at low doses (0.5 μM), CU-115 shows action against TLR7 and TLR8. Among HEK-293 TLR1/2, TLR2/6, TLR3, and TLR4 cells, CU-115 did not affect the NF-kB inhibition produced by Pam2CSK4, Pam3CSK4, Poly(I:C), LPS, R848, or Flic. Between 10 and 25 percent is the amount that CU-115 inhibits TLR9 signaling at 1, 5, and 20 µM. CU-115 (5–20 µM) suppresses the increase in type I IFN transcriptional activity caused by the ssRNA nucleic acid ligand 3p–hpRNA or G3–YSD in a luciferase reporter test. In Hek293 TLR7 and TLR8 cells, CU-115 (0.5, 1.0, 5, and 20 µM; 16 hours) is lethal at 100 µM and benign at low concentrations (0.5 and 20 µM). Additionally, at low concentrations (0.5 and 20 μM), CU-115 was harmless; but, at 100 μM, it partially harmed THP Dual cells. TNF-α upregulation/inhibition in human THP-1 cells was assessed using the enzyme-linked immunosorbent assay (ELISA) (hTHP-1). TNF-α production in hTHP1 triggered by R848 (1 µg/ml) is eliminated by CU-115 (5–20 µM). In hTHP-1 cells, it also suppresses the expression of IL-1β. These findings suggest that TLR8 and TLR7 signaling pathways are inhibited by CU-115.

References

[1]. Discovery of Novel Small Molecule Dual Inhibitors Targeting Toll-Like Receptors 7 and 8. J Med Chem. 2019 Nov 27;62(22):10221-10244.

Solubility Data

Solubility (In Vitro)

DMSO : ~100 mg/mL (~175.68 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.5 mg/mL (4.39 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	1.7568 mL	8.7841 mL	17.5682 mL
	5 mM	0.3514 mL	1.7568 mL	3.5136 mL
	10 mM	0.1757 mL	0.8784 mL	1.7568 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.