Use of caseinolytic protease p function as a biomarker of drug response to imipridone-like agents

A compound of the general Formula I:

• Z1-Q Formula I
• or a pharmaceutically acceptable salt thereof, wherein:
• Z1 is:
• Z2 is:
• Q is independently selected from the group consisting of:
• Ar1 and Ar2 are independently selected from aryl, heteroaryl, thiophenyl and phenyl;
• Ar1 may be optionally substituted with from 1 to 3 J groups;
• Ar2 is substituted with from 1 to 3 JJ groups;
• J is independently selected from halogen, —CN, (C1-C6)optionally substituted alkyl, (C3-C9)optionally substituted cycloalkyl, (C3-C9)cycloalkyl(C1-C6)alkyl, (C1-C6)haloalkyl, —CF3, —NH2, —NO2, —SH, —SR15, —OH, (C1-C6)optionally substituted alkoxy, —NR17R18, substituted (C3-C9)cycloalkyl(C1-C6)alkyl, (C3-C9)cycloalkyl(C2-C6)alkynyl, (C4-C8)cycloalkenyl, (C4-C8)cycloalkenyl(C1-C6)alkyl, aryl, heteroaryl, heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted heterocyclyl, —C(O)OH, ˜C(O)OR15, —OC(O)OR15, (C2-C6)alkynyl, (C2-C8)alkenyl, (C1-C6)haloalkyoxy, —S(O)2OR15, —SO2NR17R18, —S(O)2R15, —NR15S(O)2R16, —C(O)NR17R18, —C(O)R15, and —NR15C(O)R16;
• JJ is independently selected from halogen, —CN, (C1-C6)haloalkyl, (C1-C6)optionally substituted alkyl, —CF3, —NH2, —NO2, —SH, —SR15, —OH, (C1-C6)optionally substituted alkoxy, —NR17R18, aryl, heteroaryl, —C(O)OH, —C(O)OR15, —OC(O)OR15, (C2-C6)alkynyl, (C2-C8)alkenyl, (C1-C6)haloalkyoxy, —S(O)2OR15, —SO2NR17R18, —S(O)2R15, —NR15S(O)2R16, —C(O)NR17R18, —C(O)R15, and —NR15C(O)R16;
• R1, R2, R3, R4, R5, R6, R7 and R8 are each independently selected from hydrogen, halogen, —OH and (C1-C3) optionally substituted alkyl;
• R5 and R6 may be taken together to form ═O;
• R7 and R8 may be taken together to form ═O;
• R14 is independently selected from hydrogen, halogen, (C1-C6)optionally substituted alkyl, (C3-C6)cycloalkyl, (C1-C6)haloalkyl, (C2-C6)optionally substituted alkenyl, (C2-C6)optionally substituted alkynyl, —CN, —S(O)2R15, —NR17R18, —S(O)2R15, —C(NH)NH2, —C(O)R15, and —C(O)OR15;
• R15, R16, R17, R18 and R29 are independently selected from hydrogen and (C1-C6) optionally substituted alkyl;
• R17 and R18 together with nitrogen to which they are attached may form a ring of 3 to 6 atoms;
• W4 is independently selected from the group consisting of ═C(R14)- and nitrogen;
• A is independently selected from the group consisting of SS and
• G is independently selected from the group consisting of SS and
• M is independently selected from the group consisting of SS and
• E is independently selected from the group consisting of a single bond, SS, and
• SS is independently selected from the group consisting of:
• R20, R21, R26 and R27 are each independently selected from the group consisting of hydrogen, halogen and (C1-C6)optionally substituted alkyl;
• R22, R23, R24 and R25 are each independently selected from the group consisting of hydrogen, halogen, —CN, (C1-C6)optionally substituted alkyl, (C3-C9)optionally substituted cycloalkyl, (C3-C9)cycloalkyl(C1-C6)alkyl, (C1-C6)haloalkyl, —NH2, —NO2, —SH, —SR15, —OH, (C1-C6)optionally substituted alkoxy, —NR17R18, substituted (C3-C9)cycloalkyl(C1-C6)alkyl, (C3-C9)cycloalkyl(C2-C6)alkynyl, (C4-C8)cycloalkenyl, (C4-C8)cycloalkenyl(C1-C6)alkyl, aryl, heteroaryl, —C(O)OH, —C(O)OR15, —OC(O)OR15, (C2-C6)alkynyl, (C2-C8)alkenyl, (C1-C6)haloalkyoxy, —S(O)2OR15, —SO2NR17R18, —S(O)2R15, —NR15S(O)2R16, —C(O)NR17R18, —C(O)R15, and —NR15C(O)R16;
• R22 and R23 together with the carbon to which they are attached may form a nonaromatic ring having 3 to 6 carbon atoms;
• R22 and R23 together with the carbon to which they are attached may form a nonaromatic ring having 1-2 oxygen atoms;
• R24 and R25 together with the carbon to which they are attached may form a nonaromatic ring having 1-2 oxygen atoms;
• R24 and R25 together with the carbon to which they are attached may form a nonaromatic ring having 3 to 6 carbon atoms;
• R30 and R31 are each is independently selected from the group consisting of hydrogen and (C1-C6)optionally substituted alkyl.