Patent ID: 8741572

Claim:
A method for screening for a compound that modulates human mIGF1 translation that is regulated by the untranslated regions (UTRs) of the human mIGF1 mRNA, the method comprising: (a) contacting a compound with a first host cell engineered to express a first reporter protein translated from a first mRNA transcript comprising a first reporter gene coding sequence operably linked to a first 5′-UTR of human mIGF1 encoded by the nucleotide sequence of SEQ ID NO:1 and a first 3′-UTR of human mIGF1 encoded by the nucleotide sequence of SEQ ID NO:2, wherein the first 5′-UTR is upstream of the first reporter gene coding sequence and the first 3′-UTR is downstream of the first reporter gene coding sequence, and wherein the first reporter gene coding sequence is not mIGF1, and wherein at least one compound is 4-(4-aminophenylthio)-6-chloropyrimidin-2-amine, N,N-dimethyl-4-(5-nitro-1H-benzo[d]imidazol-2-yl)aniline, 1-chloro-3-propyl-benzoimidazo[1,2-a]pyridine-4-carbonitrile, 3-(2,3-dihydro-1H-benzo[f]cyclopenta[c]quinolin-4-yl)phenol, N-(4-(benzo[d]thiazol-2-yl)phenylcarbamothioyl)-4-ethoxy-3-nitrobenzamide, 2-amino-4-(3-(trifluoromethyl)phenyl)-4H-benzo[h]chromene-3-carbonitrile, or N-(5-(benzo[d]thiazol-2-yl)-2-methylphenylcarbamothioyl)-4-butoxybenzamide; and (b) contacting the compound with a second host cell engineered to express a second reporter protein translated from a second mRNA transcript comprising the first reporter gene coding sequence operably linked to a second 5′-UTR and a second 3′-UTR of a mRNA different from the first 5′-UTR of human mIGF1 and the first 3′-UTR of human mIGF1, wherein the second 5′-UTR is upstream of the first reporter gene coding sequence and the second 3′-UTR is downstream of the first reporter gene coding sequence; and (c) detecting the amount or activity of the first and second reporter proteins, wherein (i) an alteration in the amount or activity of the first reporter protein in the presence of the compound relative to the amount or activity of the first reporter protein in the absence of the compound or the presence of a negative control, and (ii) no alteration in or not a substantially altered amount or activity of the second reporter protein in the presence of the compound relative to the amount or activity of the second reporter protein in the absence of the compound or the presence of the negative control indicates that the compound modulates human mIGF1 translation that is regulated by the UTRs of human mIGF1 mRNA.