Table 1

Structure-activity relationships of 13 boronic acid proteasome inhibitors against purified proteasome activity (Ki) and their ability to inhibit cell growth across 60 tumor cell lines (average GI50) from the National Cancer Institute

Compound (NSC no./PS no.)StructureKi (nm)Average GI50 (nm)
681226/PS-273MorphCONH(CHNaphthyl)CONH(CHisobutyl)B(OH)20.26.3
681227/PS-293Enantio-PS-2732,30056,000
681228/PS-2968-Quinolyl sulfonylCONH(CHNaphthyl)CONH(CHisobutyl)B(OH)23.517
681229/PS-303NH2(CHNaphthyl)CONH(CHisobutyl)B(OH)21268
681231/PS-305MorphCONH(sCHNaphthyl)CONH(CHisobutyl)B(OH)21894,700
681234/PS-313NaphthylCH2CH2CONH(CHisobutyl)B(OH)2581,300
681236/PS-321MorphCONH(CHNaphthyl)CONH(CHPhe)B(OH)20.56.6
681237/PS-334CH3NH(CHNaphthyl)CONH(CHisobutyl)B(OH)23.513
681239/PS-341PyrazylCONH(CHPhe)CONH(CHisobutyl)B(OH)20.63.9
681242/PS-364PheCH2CH2CONH(CHisobutyl)B(OH)21,50010,000
683086/PS-3252-QuinolylCONH(CHhomoPhe)CONH(CHisobutyl)B(OH)2234
683094/PS-352PheCH2CH2CONH(CHPhe)CONH(CHisobutyl)B(OH)20.110
683098/PS-383PyridylCONH(CHpFPhe)CONH(CHisobutyl)B(OH)20.610