| CPC C07K 16/18 (2013.01) [A61K 31/40 (2013.01); A61K 31/439 (2013.01); A61P 35/00 (2018.01); G01N 33/574 (2013.01); A61K 45/06 (2013.01)] | 4 Claims |
|
1. A method for predicting a therapeutic effect of a chemotherapy using an antitumor agent comprising an LSD1 inhibitor in a cancer patient, comprising
obtaining a sample containing tumor cells from said cancer patient,
measuring INSM1 expression in said sample,
determining that the expression level of INSM1 is equal to or higher than a predetermined cut-off point, and
administering said antitumor agent comprising an LSD1 inhibitor to said cancer patient,
wherein the LSD1 inhibitor is a biphenyl compound represented by Formula (I) below,
 wherein:
ring A represents pyrrolidinyl, piperidinyl, piperazinyl, azepanyl, diazepanyl,
 2,7-diazaspiro[3.4]octanyl, 3,7-diazaspiro[3.4]octanyl, 2,7 diazaspiro[3.5]nonanyl, 2,8-diazaspiro[3.5]nonanyl, 3,7-diazaspiro[3.5]nonanyl, 3,8-diazaspiro[4.4]nonanyl, 3,8-diazaspiro[4.5]decanyl, or 9-oxa-diazaspiro[3.5]nonanyl;
ring B represents phenyl, naphthyl, pyridyl, pyrazolopyridyl,
pyrazolopyrimidinyl, indolyl, indolinyl, 2-oxo-indolinyl, indazolyl,
benzoimidazolyl, benzoisoxazolyl, benzothiazolyl, benzotriazolyl,
imidazopyridinyl, quinolinyl, isoquinolinyl, quinoxalinyl, quinazolinyl,
phthalazinyl, 2-oxo-2,3-dihydrobenzo[d]oxazolyl, 1,3-dihydroisobenzofuranyl,
dihydrobenzooxazinyl, benzodioxolyl, dihydrobenzodioxynyl, or 2-oxo-2,3-dihydrobenzo[d]thiazolyl,
R1 represents nitro or cyano;
R2 represents fluorine, and is present at the ortho position relative to R1 on the phenyl;
R3 represents amino, methylamino, ethylamino, isopropylamino, dimethylamino, cyclobutylamino, or methyl, wherein when two or more R3s are present, R3s may be identical or different;
R4 represents fluorine, chlorine, bromine, iodine, nitro, cyano, carboxy, methyl, ethyl, n-propyl, isopropyl, tert-butyl, difluoromethyl, trifluoromethyl, fluoroethyl, aminoethyl, hydroxymethyl, hydroxyethyl, hydroxypropyl, hydroxydimethylethyl, hydroxymethylpropyl, hydroxymethylbutyl, hydroxyethylbutyl, carboxymethyl, carbamoylmethyl, methylcarbamoylmethyl, dimethylcarbamoylmethyl, acetylaminoethyl, methoxyethyl, hydroxycyclopropylmethyl, hydroxycyclopropylethyl, hydroxycyclobutylmethyl, methylcarbonyloxyethyl, isobutenyl, methoxy, hydroxypropoxy, cyclopropyl, hydroxymethyl cyclopropyl, methoxymethyl cyclopropyl, hydroxycyclopropyl cyclopropyl, phenylcarbamoyl cyclopropyl, benzyloxy, dimethylamino, carbamoyl, methylcarbamoyl, or
dimethylcarbamoyl, wherein when two or more R4s are present, R4s may be identical or different;
R5 and R6 may be identical or different, and each represent hydrogen or C1-C6 alkyl;
R5 and R6 may otherwise form oxo or thioxo together;
when R5 and R6 are identical or different, and each represent hydrogen or
C1-C6 alkyl, at least one of R5 and R6 is hydrogen;
l represents an integer of 0 to 2;
m represents an integer of 0 to 2;
n represents an integer of 0 to 3;
when l is 2, two R2s may be identical or different;
when m is 2, two R3s may be identical or different; and
when n is 2 to 3, two to three R4s may be identical or different,
or a salt thereof, GSK2879552, ORY-1001, or GSK690.
|