Fused tricyclic pyrimidine-thieno-pyridine small molecule inhibitors of ubiquitin-specific protease 28

A compound of formula (I)

• or a pharmaceutically acceptable salt thereof, wherein:
• X1 is N;
• R1 is H or C1-5 alkyl;
• X2 is CR2;
• is a double bond;
• X3 is —CR3—;
• R2 and R3 are each independently H, halogen, —C(halogen)3, —C(═O)NR13R14, or C1-3 alkyl, or
• R2 and R3, together with the carbon atoms to which they are attached, form a 5-membered or a 6-membered carbocyclyl;
• or
• R1 and R2 together with the carbon atoms to which they are attached, form a 5-membered or a 6-membered carbocyclyl;
• R13 and R14 are each independently C1-3 alkyl, or
• R13 and R14, together with the nitrogen atom to which they are attached, form a 5- or a 6-membered heterocyclyl;
• Y1 is —S—;
• Y2 is H or —NR9R10;
• R9 is C1-2 alkyl, C7-10 aralkyl, or —C(═O)C1-2 alkyl;
• R10 is H or C1-2 alkyl, or
• R9 and R10, together with the atoms to which they are attached, form a 5-membered heterocyclyl or heteroaryl,
• Z1 is —C(═O)— or —C(═NR11)—;
• R11 is H or C1-2 alkyl, or Y2 and R11, together with the atoms to which they are attached, form a 5-membered or a 6-membered heterocyclyl or heteroaryl;
• Z4 is —NR5— or —O—;
• R5 is H or C1-2 alkyl;
• Z is a bond or C1-4 alkylene;
• Z3 is C5-7 cycloalkyl, C6 aryl, or 5- to 10-membered heteroaryl, wherein the C6 aryl is optionally substituted with one or more group selected from halogen, —OH, C1-2 alkoxyl, —N(R8)2, —S(═O)2NH2, and 5- to 10-membered heterocyclyl, wherein the 5- to 10-membered heterocyclyl is optionally substituted with one or more R4;
• or wherein the C6 aryl is optionally fused to a 5-membered or 6-membered heterocyclyl, wherein the 5-membered or 6-membered heterocyclyl is optionally substituted with one or more R4;
• and
• R4 is —C(═O)OC1-5 alkyl,
• provided the compound is not