Proteolysis targeting chimera compound

A compound represented by formula (I), or a pharmaceutically acceptable salt, a stereoisomer, a tautomer, a cis-trans isomer, a solvate, a hydrate, a polymorph, a prodrug or an isotope variant thereof, and a mixture thereof:

• wherein,
• the POI is
• represents a single bond or a double bond, alternatively a double bond;
• each RP is independently selected from H, D, halogen, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl and C2-6 alkynyl;
• s is selected from 1, 2 and 3;
• XP is selected from N and CRP;
• W is selected from H, D, halogen, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl and 5- to 10-membered heteroaryl;
• said W is optionally substituted with 1, 2 or 3 RW;
• RW is selected from H, D, —C(O)Ra, —C(O)NRbRc, —C(O)ORa, —OC(O)Ra, —NRbC(O)Ra, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl and C2-6 alkynyl;
• the a-terminal of the POI is connected to Q via C0-3 alkylene, and the b-terminal is connected to L;
• L is
• represents a single bond, a cis- or trans-double bond, alternatively a cis-double bond;
• each XL is independently selected from a chemical bond, —O—, C1-6 alkylene, C2-6 alkenylene, C2-6 alkynylene, C3-10 cycloalkylene, 5- to 10-membered heterocyclylene, C6-10 arylene and 5- to 10-membered heteroarylene;
• the XL is optionally deuterated, up to completely deuterated;
• each m is independently selected from 0, 1, 2, 3, 4, 5, 6, 7, 8, 9 and 10;
• each n is independently selected from 0, 1, 2, 3, 4, 5, 6, 7, 8, 9 and 10;
• each p is independently selected from 0, 1, 2, 3, 4 and 5;
• each q is independently selected from 1, 2, 3, 4 and 5;
• the b-terminal of L is connected to POI, and the c-terminal is connected to E3, or the c-terminal of L is connected to POI, and the b-terminal is connected to E3;
• E3 is
• RE1, RE2, RE3 or RE4 are independently selected from H and D, and at least one pair of RE1 and RE2, RE3 and RE4 represents ═O, ═S or ═N—OH;
• the c-terminal of E3 is connected to L, and the d-terminal is connected to Q via C0-3 alkylene;
• Q is
• L1 and L2 are independently selected from NH and O;
• XQ is selected from —P(O)(YQ—RQ)—, —S(O)— and —C(O)—XQ1—C(O)—;
• YQ is selected from NH and O;
• XQ1 is selected from a chemical bond, C1-6 alkylene, C2-6 alkenylene, C2-6 alkynylene, —C1-6 alkylene-O—C1-6 alkylene, —C1-6 alkylene-NRb—C1-6 alkylene, C3-10 cycloalkylene, 5- to 10-membered heterocyclylene, C6-10 arylene and 5- to 10-membered heteroarylene, and the XQ1 is optionally substituted with 1, 2, 3, 4 or 5 independently selected R #;
• RQ is selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, 5-to 10-membered heterocyclyl, C6-10 aryl and 5- to 10-membered heteroaryl;
• Ra, Rb and Rc are independently selected from H, C1-6 alkyl and C1-6 haloalkyl;
• R # is selected from H, halogen, OH, NH2, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl and C2-6 alkynyl.