PD 404182

PD 404182 is an antiviral agent.^1,2 It inhibits the activity of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) main protease (M^pro), also known as 3C-like protease (3CL^pro; IC₅₀ = 0.081 µM), and prevents herpes simplex virus 1 (HSV-1) and HSV-2 infection in Vero cells when used at a concentration of 0.2 µM. PD 404182 also inhibits dimethylarginine dimethylaminohydrolase 1 (DDAH-1) and histone deacetylase 8 (HDAC8; IC₅₀s = 9 and 0.011 µM for the human enzymes, respectively), as well as bacterial KDO 8-P synthase (K_i = 0.026 µM), an enzyme important for LPS biosynthesis.^3,4,5 It reduces endothelial tube formation and LPS-induced nitric oxide (NO) production in primary human dermal microvascular endothelial cells.³

WARNING This product is not for human or veterinary use.

1. Brown, A.S., Ackerley, D.F., and Calcott, M.J. High-throughput screening for inhibitors of the SARS-CoV-2 protease using a FRET-biosensor. Molcecules 25(20), 4666 (2020).

2. Chamoun-Emanuelli, A.M., Bobart, M., Moncla, B., et al. Evaluation of PD 404,182 as an anti-HIV and anti-herpes simplex virus microbicide. Antimicrob. Agents Chemother. 58(2), 687-697 (2014).

3. Ghebremariam, Y.T., Erlanson, D.A., and Cooke, J.P. A novel and potent inhibitor of dimethylarginine dimethylaminohydrolase: a modulator of cardiovascular nitric oxide. J. Pharmacol. Exp. Ther. 348(1), 69-76 (2014).

4. Kleinschek, A., Meyners, C., Digiorgio, E., et al. Potent and selective non-hydroxamate histone deacetylase 8 inhibitors. ChemMedChem 11(23), 2598-2606 (2016).

5. Birck, M.R., Holler, T.P., and Woodard, R.W. Identification of a slow tight-binding inhibitor of 3-deoxy-d-manno-octulosonic acid 8-phosphate synthase. J. Am. Chem. Soc. 122, 9334-9335 (2000).