SPD304 dihydrochloride

SPD304 dihydrochloride is a selective TNF-α inhibitor, which promotes dissociation of TNF trimers and therefore blocks the interaction of TNF and its receptor. SPD304 has an IC50 of 22 µM for inhibiting in vitro TNF receptor 1 (TNFR1) binding to TNF-α.

Product information

CAS Number: 1049741-03-8

Molecular Weight: 620.53

Formula: C32H34Cl2F3N3O2

Chemical Name: 6, 7-dimethyl-3-{[methyl({2-[methyl({1-[3-(trifluoromethyl)phenyl]-1H-indol-3-yl}methyl)amino]ethyl})amino]methyl}-4H-chromen-4-one dihydrochloride

Smiles: Cl.Cl.CC1=CC2OC=C(CN(C)CCN(C)CC3=CN(C4=CC=CC=C34)C3=CC(=CC=C3)C(F)(F)F)C(=O)C=2C=C1C

InChiKey: GOZMBJCYMQQACI-UHFFFAOYSA-N

InChi: InChI=1S/C32H32F3N3O2.2ClH/c1-21-14-28-30(15-22(21)2)40-20-24(31(28)39)18-37(4)13-12-36(3)17-23-19-38(29-11-6-5-10-27(23)29)26-9-7-8-25(16-26)32(33,34)35;;/h5-11,14-16,19-20H,12-13,17-18H2,1-4H3;2*1H

Technical Data

Appearance: Solid Power

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

Solubility: Soluble in DMSO

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:

SPD304 (2 μM) significantly rescues the survivability of aHSCs, reduces the production of lipid hydroxides, and increased intracellular GSH. The co-treatment of GA (75 μM) and SPD304 (2 μM), down-regulate TRADD almost 2-fold (w/o inhibitor vs. w/ inhibitor) and p−RIP3 1.4−fold compared to GA alone, and promotes caspase 8 activation.

In Vivo:

SPD304 cannot be used in vivo due to its high toxicity.

References:

1. Molly M. He, et al. Small-Molecule Inhibition of TNF-α. Science 11 Nov 2005.
2. Alexiou P, et al. Rationally designed less toxic SPD-304 analogs and preliminary evaluation of their TNF inhibitory effects. Arch Pharm (Weinheim). 2014 Nov;347(11):798-805.
3. Mouhsine H, et al. Identification of an in vivo orally active dual-binding protein-protein interaction inhibitor targeting TNFα through combined in silico/in vitro/in vivo screening. Sci Rep. 2017 Jun 13;7(1):3424.

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