Selective inhibitors of undifferentiated cells
AssigneesYissum Research Development Company of the Hebrew University of Jerusalem, Hoffmann-La Roche Inc.
InventorsUri Ben-David, Nissim Benvenisty, Payal Arora, Qing-Fen Gan, Ralph J. Garippa
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Abstract
Uses of a compound of any of Formulas I-VI as a cytotoxic inhibitor of undifferentiated cells are disclosed herein, as well as pharmaceutical compositions comprising a compound of any of Formulas I-VI, and methods for identifying a lead candidate for inhibiting undifferentiated cells. Further disclosed are uses of an SCD-1 inhibitor as a cytotoxic inhibitor of undifferentiated cells.
Claims23
1-22. (canceled)
A method of inhibiting undifferentiated cells, the method being effected by contacting undifferentiated cells with a compound selected from the group consisting of:
- a compound of Formula I
- a compound of Formula II
- a compound of Formula III
- a compound of Formula IV
- a compound of Formula V
- and
- a compound of Formula VI
- wherein:
- R1 is hydrogen, and
- R2 is selected from the group consisting of:
- hydrogen,
- 2,4-dioxo-5-fluoropyrimidin-1-ylcarbonyl,
- 2-methylbenzofuran-3-ylmethyleneamino,
- and
- —NH—R5, wherein R5 is selected from the group consisting of:
- pyridinylcarbonyl,
- 2-hydroxyl-2-phenyl-2-thiophen-2-yl-acetyl,
- (C1-6)alkyl-carbonyl,
- N-(ethoxycarbonylmethyl)-2,4-dioxo-pyrrolidine-3-ylidene-methyl,
- naphthylsulfonyl, and
- N-hydroxy-acetimidoyl;
- or wherein:
- R1 is benzoyl and R2 is 4-chlorobenzamido;
- and
- R3 and R4 are independently selected from the group consisting of hydrogen, halo, NH2, biphenyloxymethyl and (C1-4)alkyl,
- with the proviso that at least one of R1, R2, R3 and R4 is not hydrogen, halo, NH2 or (C1-4)alkyl.
A pharmaceutical composition comprising:
- a) a therapeutically effective amount of a compound selected from the group consisting of:
- a compound of Formula I
- a compound of Formula II
- a compound of Formula III
- a compound of Formula IV
- a compound of Formula V
- and
- a compound of Formula VI
- and
- b) a pharmaceutically acceptable carrier.
A method of treating a proliferative disease or disorder associated with proliferation of undifferentiated cells in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of a compound selected from the group consisting of:
- a compound of Formula I
- a compound of Formula II
- a compound of Formula III
- a compound of Formula IV
- a compound of Formula V
- and
- a compound of Formula VI
- thereby treating the proliferative disease or disorder.
A method of identifying a lead candidate for inhibiting pluripotent stem cells, the method comprising:
- (a) providing a plurality of samples of pluripotent stem cells, each of said samples comprising a different type of pluripotent stem cells;
- (b) contacting said samples with a candidate compound;
- and
- (c) monitoring a viability of said stem cells in said samples, whereby if said viability is reduced in at least two of said samples, said candidate compound is identified as capable of inhibiting pluripotent stem cells, thereby identifying the lead candidate.
A method of inhibiting pluripotent stem cells, the method being effected by contacting pluripotent stem cells with an SCD1 (Stearoyl-CoA desaturase-1) inhibitor.
Dependencies are inferred from the claim text.