GSK3494245

• CAT Number: I028369
• CAS Number: 2080410-41-7
• Molecular Formula: C21H23FN6O2
• Molecular Weight: 410.45
• Purity: 98%
• Synonyms: GSK3494245; GSK 3494245; GSK-3494245; DDD01305143; DDD-01305143; DDD 01305143
• Target: Metabolic Enzyme/Protease
• Solubility: Soluble in DMSO
• Appearance: Solid powder
• Storage: Store at -20°C
• IUPAC Name: N-[4-fluoro-3-(3-morpholin-4-ylimidazo[1,2-a]pyrimidin-7-yl)phenyl]pyrrolidine-1-carboxamide
• InChI: InChI=1S/C21H23FN6O2/c22-17-4-3-15(24-21(29)27-6-1-2-7-27)13-16(17)18-5-8-28-19(14-23-20(28)25-18)26-9-11-30-12-10-26/h3-5,8,13-14H,1-2,6-7,9-12H2,(H,24,29)
• InChIKey: SAJUCKZZYFFICP-UHFFFAOYSA-N
• SMILES: C1CCN(C1)C(=O)NC2=CC(=C(C=C2)F)C3=NC4=NC=C(N4C=C3)N5CCOCC5

GSK3494245（Cat No.:I028369）, also known as DDD01305143, is a potent, orally active inhibitor targeting the chymotrypsin-like activity of the Leishmania donovani proteasome, with an IC₅₀ of 0.16 μM.It binds selectively between the β4 and β5 subunits of the parasite’s proteasome, disrupting protein degradation essential for parasite survival. In preclinical studies, GSK3494245 demonstrated significant efficacy, achieving over 95% reduction in parasite load in infected mice.Its moderate inhibition of human proteasome activity (IC₅₀ of 13 μM for purified 26S) suggests a favorable safety profile.These attributes position GSK3494245 as a promising candidate for treating visceral leishmaniasis.

Reference

1: Wyllie S, Brand S, Thomas M, De Rycker M, Chung CW, Pena I, Bingham RP, Bueren-Calabuig JA, Cantizani J, Cebrian D, Craggs PD, Ferguson L, Goswami P, Hobrath J, Howe J, Jeacock L, Ko EJ, Korczynska J, MacLean L, Manthri S, Martinez MS, Mata-Cantero L, Moniz S, Nühs A, Osuna-Cabello M, Pinto E, Riley J, Robinson S, Rowland P, Simeons FRC, Shishikura Y, Spinks D, Stojanovski L, Thomas J, Thompson S, Viayna Gaza E, Wall RJ, Zuccotto F, Horn D, Ferguson MAJ, Fairlamb AH, Fiandor JM, Martin J, Gray DW, Miles TJ, Gilbert IH, Read KD, Marco M, Wyatt PG. Preclinical candidate for the treatment of visceral leishmaniasis that acts through proteasome inhibition. Proc Natl Acad Sci U S A. 2019 May 7;116(19):9318-9323. doi: 10.1073/pnas.1820175116. Epub 2019 Apr 8. PMID: 30962368; PMCID: PMC6511062.