A compound of Formula I: ##STR00001##
wherein: X.sup.1-X.sup.8 are each independently C or N, wherein two adjacent X.sup.1-X.sup.8 are carbon-fused to a structure of Formula II: ##STR00002## X.sup.9-X.sup.12 are each independently C or N; A.sup.1, A.sup.2, and A.sup.3 are each independently selected from the group consisting of O, S, Se, N, NR, CR, CRR′, SiR, SiRR′, GeR, and GeRR′, with at least one of A.sup.1 and A.sup.2 being N or NR; each occurrence of is independently a single bond or a double bond, wherein one occurrence of is a single bond and one occurrence of is a double bond; each of R.sup.A, R.sup.B, and R.sup.c independently represents zero, mono, or up to a maximum allowed substitution to its associated ring; each of occurrence R, R′, R.sup.A, R.sup.B, and R.sup.C is independently a hydrogen or a substituent selected from the group consisting of Formula III, Formula IV, Formula V, Formula VI, Formula VII, Formula VIII, Formula IX, deuterium, halogen, alkyl, cycloalkyl, heteroalkyl, heterocycloalkyl, arylalkyl, alkoxy, aryloxy, amino, silyl, boryl, alkenyl, cycloalkenyl, heteroalkenyl, alkynyl, aryl, heteroaryl, acyl, carboxylic acid, ether, ester, nitrile, isonitrile, sulfanyl, sulfinyl, sulfonyl, phosphino, and combinations thereof, with at least one of R, R′, R.sup.A, R.sup.B, and R.sup.C comprising a group of Formula III, Formula IV, Formula V, Formula VI, Formula VII, Formula VIII, or Formula IX: ##STR00003## ##STR00004## each occurrence of Y.sup.1, Y.sup.2, and Y.sup.3 is independently absent, O, S, Se, NR, CRR′, SiRR′, or GeRR′; each occurrence of Ar.sup.1, and Ar.sup.2 is independently an optionally substituted aryl group or an optionally substituted heteroaryl group, wherein Ar.sup.1 and Ar.sup.2 are optionally joined or fused together to form a ring; each occurrence of X.sup.13-X.sup.20 is independently C or N, with the proviso that at least one of X.sup.13-X.sup.20 is N; each occurrence of A.sup.4 is selected from the group consisting of O, S, Se, NR, CRR′, SiRR′, and GeRR′; each occurrence of R.sup.X independently represents zero, mono, or up to a maximum allowed substitution to its associated ring; each occurrence of R.sup.X is in

The present invention relates to a targeted protease degradation (TED) platform, and specifically to a conjugate of target molecule-linker-E3 ligase ligand as shown in formula I, R.sub.T-L1-R.sub.E3 (formula I), wherein R.sub.T is a monovalent group of the target molecule, R.sub.E3 is a monovalent group of the E3 ligase ligand, L1 is the linker linking A and B, and L1 is as shown in formula II below: —W-L2-W.sup.2— (II).

Disclosed herein are methods and compounds for inducing DDB1- and CUL4-associated factor 16 (DCAF16)-mediated protein degradation in mammalian cells. In some embodiments, also disclosed herein are methods of modulating the substrate selectivity of a DCAF16-CUL4-RBX1-DDB1 complex (CRL4) for modulating protein degradation.

Disclosed herein are methods and compounds for inducing DDB1- and CUL4-associated factor 16 (DCAF16)-mediated protein degradation in mammalian cells. In some embodiments, also disclosed herein are methods of modulating the substrate selectivity of a DCAF16-CUL4-RBX1-DDB1 complex (CRL4) for modulating protein degradation.

Provided are a compound superior in a cytotoxic action on cancer cells, an action inducing degradation of BET protein in cancer cells, and an inhibitory action on the binding of BET protein and acetylated histone, and useful as an anticancer agent, a BET protein degradation inducer or a BET protein inhibitor. A compound represented by the following formula (I) ##STR00001##
wherein each symbol is as defined in the specification, or a pharmacologically acceptable salt thereof.

Provided are a compound superior in a cytotoxic action on cancer cells, an action inducing degradation of BET protein in cancer cells, and an inhibitory action on the binding of BET protein and acetylated histone, and useful as an anticancer agent, a BET protein degradation inducer or a BET protein inhibitor. A compound represented by the following formula (I) ##STR00001##
wherein each symbol is as defined in the specification, or a pharmacologically acceptable salt thereof.

There are provided new heterobifunctional agents designed to mediated formation of protein-protein dimers and promote ubiquitination of a protein of the dimer. Also provided are methods of synthesizing the agents, pharmaceutical formulations including the agents, and methods of using the agents to treat, ameliorate or cure diseases characterized by protein over-expression or malfunction.

There are provided new heterobifunctional agents designed to mediated formation of protein-protein dimers and promote ubiquitination of a protein of the dimer. Also provided are methods of synthesizing the agents, pharmaceutical formulations including the agents, and methods of using the agents to treat, ameliorate or cure diseases characterized by protein over-expression or malfunction.

A material comprising a group of formula (I): (I) wherein: X and Y are each independently selected from S, O or Se; Ar1, Ar2, Ar3 and Ar4 are each independently an unsubstituted or a substituted benzene, an unsubstituted or a substituted 5- or 6-membered heteroaromatic group or are absent; A.sup.1 and A.sup.2 are each independently an unsubstituted or a substituted benzene, an unsubstituted or a substituted 5- or 6-membered heteroaromatic group, a non-aromatic 6-membered ring having ring atoms selected from C, N, S and O or are absent; R.sup.1 is H or a substituent; R.sup.2 and R.sup.3 are each independently H or a substituent; and * represents a point of attachment to a hydrogen or non-hydrogen substituent.

##STR00001##

A material comprising a group of formula (I): (I) wherein: X and Y are each independently selected from S, O or Se; Ar1, Ar2, Ar3 and Ar4 are each independently an unsubstituted or a substituted benzene, an unsubstituted or a substituted 5- or 6-membered heteroaromatic group or are absent; A.sup.1 and A.sup.2 are each independently an unsubstituted or a substituted benzene, an unsubstituted or a substituted 5- or 6-membered heteroaromatic group, a non-aromatic 6-membered ring having ring atoms selected from C, N, S and O or are absent; R.sup.1 is H or a substituent; R.sup.2 and R.sup.3 are each independently H or a substituent; and * represents a point of attachment to a hydrogen or non-hydrogen substituent.

##STR00001##