UCB-9260 (UCB9260; UCB 9260) is an oral anti-inflammatory drug that may be used to treat autoimmune conditions like Crohn's disease and rheumatoid arthritis. It functions as a TNF inhibitor, preventing TNF signaling by maintaining an asymmetric form of the trimer. After stimulating Hek-293 cells with TNF (10 pM), UCB-9260 inhibits NF-κB in vitro with a geometric mean IC50 of 202 nM. In a mouse rheumatoid arthritis-CIA model, UCB-9260 significantly lowers the clinical score in vivo.

Physicochemical Properties

Molecular Formula	C26H25N5O
Molecular Weight	423.509605169296
Exact Mass	423.21
Elemental Analysis	C, 73.74; H, 5.95; N, 16.54; O, 3.78
CAS #	1515888-53-5
Related CAS #	1515888-53-5
PubChem CID	72700327
Appearance	Brown to gray solid
LogP	3.5
Hydrogen Bond Donor Count	1
Hydrogen Bond Acceptor Count	4
Rotatable Bond Count	5
Heavy Atom Count	32
Complexity	613
Defined Atom Stereocenter Count	0
InChi Key	RZGFWGNCSYUEPR-UHFFFAOYSA-N
InChi Code	InChI=1S/C26H25N5O/c1-17-4-5-18(2)21(12-17)16-31-24-13-20(22-14-28-30(3)15-22)6-7-23(24)29-26(31)25(32)19-8-10-27-11-9-19/h4-15,25,32H,16H2,1-3H3
Chemical Name	[1-[(2,5-dimethylphenyl)methyl]-6-(1-methylpyrazol-4-yl)benzimidazol-2-yl]-pyridin-4-ylmethanol
Synonyms	UCB-9260; UCB9260; UCB 9260
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

Targets	TNF (Kd = 13 nM); NF-κB (Kd = 202 nM)
ln Vitro	UCB-9260 (0-10 μM) inhibits NF-κB with a geometric mean IC50 of 202 nM after TNF (10 pM) stimulation in in Hek-293 cells[1]. UCB-9260 inhibits TNF-dependent cytotoxicity with a geometric mean IC50 of 116 nM and a geometric mean IC50 of 120 nM, using human and mouse TNF, respectively.
ln Vivo	UCB-9260 (150 mg/kg; p.o.;twice daily for 7 days) shows a significant reduction of the clinical score. UCB-9260 (10-300 mg/kg; p.o.) dose-dependently inhibits human and mouse TNF-induced neutrophil recruitment to the peritoneal compartment in adult male Balb/c mice[1]. Animal Model: Aged 6-8 weeks adult male Balb/c mice ( CAIA model Dosage: 150 mg/kg Administration: p.o.; twice daily for 7days Result: Showed a significant reduction of the clinical score.
References	[1]. Small molecules that inhibit TNF signalling by stabilising an asymmetric form of the trimer.Nat Commun. 2019 Dec 19;10(1):5795.

Solubility Data

Solubility (In Vitro)

DMSO: 85~125 mg/mL (200.7~295.2 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 6.25 mg/mL (14.76 mM) (saturation unknown) in 10% DMSO + 40% PEG300 +5% Tween-80 + 45% Saline (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 62.5 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 + to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.3612 mL	11.8061 mL	23.6122 mL
	5 mM	0.4722 mL	2.3612 mL	4.7224 mL
	10 mM	0.2361 mL	1.1806 mL	2.3612 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.