GNE-0011 is a monovalent, JQ1-based BRD4 degrader that is not linked to an E3 ligase binder, triggers proteasomal and ubiquitin-dependent selective degradation of BRD4 over BRD2 and BRD3.

TCIP1 is the most potent transcriptional/epigenetic CIP (chemical inducers of proximity) and specifically activates BCL6 target genes. TCIP1 kills diffuse large B cell lymphoma cell lines, including chemotherapy-resistant, TP53-mutant lines and exhibits cell-specific and tissue-specific effects. TCIP1 successfully killed large B cell lymphoma cell lines, including chemotherapy-resistant TP53-mutant lines and exhibited cell-specific and tissue-specific effects. The activation of apoptosis to cell death took place in just 72 hours.BCL6 is critical to the lymphatic system, and mice engineered without the BCL6 gene die of complex inflammatory reactions. BRD4 is heavily involved in genome function and stability across many processes. Concerns regarding utilizing these important gene expressions and how they might affect off-target healthy tissues were addressed in the study.TCIP1 acts in a context-specific manner requiring the expression of BRD4 and BCL6 to both be present in order to bind them and operate at a concentration that would occupy only a tiny fraction of the total BCL6 molecules.TCIP1 induced dramatic transcriptomic changes in the spleen, notably with an upregulation of the FOXO3 gene, which mirrored activity in the targeted cancer cells. Despite the significant transcriptomic changes in the spleen, TCIP1 was well tolerated without adverse effects, with no significant differences in mouse body weight and no noticeable abnormalities such as inflammatory infiltrates or apoptotic cells. BCL6-BRD4 TCIP1 (TCIP1) is a potent BCL6-BRD4 transcriptional/epigenetic chemical inducer of proximity (TCIP) by covalently linking BCL6 binder BI-3812 to BRD4 ligand JQ1, selectively kills DLBCL cells with EC50 of 1.3 nM against KARPAS422 cell. TCIP1 rapidly and robustly killed other DLBCL lines with high levels of BCL6, but JQ1 and BI3812 separately or together shows100–1,000-fold less-effective cell killing. TCIP1 is 200–10,000-fold more potent in killing DLBCL cells than the degradation of BRD4 by dBET1 and/or degradation of BCL6 by BI3802. TCIP1 induces a stable, cooperative protein-protein interaction between bromodomain 1 (BD1) of BRD4 and the BTB domain of BCL6. TCIP1 shows affinity for intracellular ternary complex of BRD4 with Kd of 340 nM in TR-FRET assays. TCIP1 induces G1/S and G2/M block in the cell cycle, TCIP1 (10 nM) represses MYC and its targets while activating pro-apoptotic genes in KARPAS422 cells. TCIP1 kills diffuse large B cell lymphoma cell lines, including chemotherapy-resistant, TP53-mutant lines, at EC50 of 1-10 nM in 72 h and exhibits cell-specific and tissue-specific effects, capturing the combinatorial specificity inherent to transcription.

DSPE-PEG14-COOH is a PEG-based PROTAC linker that can be used in the synthesis of PROTACs.

DSPE-PEG2-mal is a PEG-based PROTAC linker that can be used in the synthesis of PROTACs.

BSJ-05-037 is a potent and selective heterobifunctional degrader of ITK with DC50 of 17.6-41.8 nM in TCL lines DERL-2 and Hut78.

PROTAC BRD4 Degrader-13 (compound 9d) is a potent chimeric BRD4 degrader. PROTAC BRD4 Degrader-13 can be conjugated with STEAP1 and CLL1 antibodies to degrade the BRD4 protein in PC3 prostate cancer cells, with a DC50 of 0.025 nM and 6.0 nM, respectively.

MS40 is a cereblon (CRBN)-based proteolysis targeting chimera (PROTAC) degrader of the onco-target WD repeat domain 5 (WDR5) [1]. WDR5 is an integral component of the MLL/KMT2A lysine methyltransferase protein complex. The WDR5-binding component of MS40 is the selective inhibitor OICR-9429, and the CRBN-targeting moiety is the immunomodulatory drug pomalidomide. MS40 promotes degradation of WDR5 and the pomalidomide transcription factor neo-substrates IKZF1 and IKZF3.

XY-07-35 is a potent, selective HDAC6 proteolysis targeting chimera (PROTAC) degrader with IC50 of 48.5 nM.

GMB-475 is a degrader of BCR-ABL1 tyrosine kinase based on PROTAC, overcoming BCR-ABL1-dependent drug resistance. GMB-475 targets BCR-ABL1 protein and recruits the E3 ligase Von Hippel Lindau (VHL), resulting in ubiquitination and subsequent degradation of the oncogenic fusion protein[1].

ARV-471 is a best-in-class, orally active estrogen receptor (ER) PROTAC degrader. ARV-471 is developed for the research of breast cancer.

ZZ151 (ZZ-151) is a highly potent and selective SOS1 degrader PROTAC with DC50 of 15.7 nM (Dmax=100%).

YX968 is a potent, selecive HDAC3/8 dual PROTAC degrader with DC50 of 1.7 and 6.1 nM in degrading HDAC3 and HDAC8 respectively (MDA-MD-231 cell, 8 h).

WD6305 is a potent and selective proteolysis-targeting chimera (PROTAC) degrader of METTL3-METTL14 complex with DC50 of 140 nM (METTL3), Dmax of 91.9% in Mono-Mac-6 AML cell line.

UNC7700 (UNC-7700) is a potent EED-targeted PRC2 degrader, contains a unique cis-cyclobutane linker and potently degrades all PRC2 components EED (DC50=111 nM; Dmax=84%), EZH2WT/EZH2Y641N (DC50=275 nM; Dmax=86%) and SUZ12 (Dmax=44%) in DLBCL cells.

UBX-382 (UBX382) is a potent and orally available proteolysis-targeting chimera (PROTAC) that induces potent BTK degradation in DLBCL cell line with DC50 of 4.5 nM.

U7D-1 is a selective USP7-degrading Proteolysis Targeting Chimera (PROTAC). U7D-1 showed selective and effective USP7 degradation, and maintained potent cell growth inhibition in p53 mutant cancer cells.

TMX-4153 (TMX4153) is a bivalent PIP4K2C degrader (MOLT4 cells, DC50=24 nM, Dmax=921% at 1 uM) based on TMX-4084, rapidly and selectively degrades endogenous PIP4K2C.

TMX-2172 is a potent, selective CDK2 and CDK5 dual PROTAC degrader with IC50 of 6.5 nM and 6.8 nM for CDK2/cyclin A and CDK5/p25, respectively.

TD-802 is potent, cereblon-mediated androgen receptor PROTAC degrader, effectively inducs AR protein degradation with DC50 of 12.5 nM and Emax 93% in LNCaP prostate cancer cells.

SelDeg51 (Selective Degrader of FKBP51) is a potent, selective FKBP51 PROTAC with Kd of 18 nM, Emax=90%.

QA-68-ZU81 (QA-68) is a EA-89-based BRD9 degrader that incorporates the EA-89 warhead into a cereblon (CRBN)-targeting proteolysis-targeting chimera (PROTAC).

PTD10 is a highly potent BTK PROTAC degrader with DC50 of 0.5 nM in TMD8 cells, inhibits cell growth and induces apoptosis more potently than parent molecule GDC-0853.

PROTAC dCE-1 is a potent, selective CBP/EP300 degrader targeting the histone acetyltransferase (HAT) domain, with DC50 value of 1.3 μM in LP1 cells.

PIK5-12d is a highly potent, selective, first-in-class PIKfyve PROTAC degrader, potently degrades PIKfyve protein with DC50 value of 1.48 nM and Dmax value of 97.7% in prostate cancer VCaP cells.

MTX-23 is a proteolysis targeting chimera (PROTAC) degrader of androgen receptor (AR) splice variant-7 (AR-V7) and AR-full length (AR-FL) with DC50 of 0.37 and 2 uM, respectively.

MS3227 is a proteolysis-targeting chimera (PROTAC) that targets MDM2 by recruiting the E3 ligase VHL, resulting in proteasome-dependent degradation of MDM2.

MS147 (MS 147) is the first degrader of PRC1 core components, BMI1 and RING1B, comprises an EED small-molecule binder (EED226, Cat. PC-42321) linked to a ligand of the E3 ligase von Hippel-Lindau (VHL), degrades BMI1/RING1B in an EED-, VHL-, ubiquitinatio

MS132 is a highly potent and selective VHL-recruiting WDR5 PROTAC degrader with DC50 of 92 nM in MIA PaCa-2 cells.

LL-K8-22 is a potent, selective dual degrader of of CDK8 and cyclin C (MDA-MB-468 cell DC50, 2.52 and 2.64 uM), significantly degrades CDK8 without reducing CDK19 and does not degrade other cyclin proteins.

KYH1872 is a PROTAC that induces protein degradation via the KLHDC2 E3 ubiquitin ligase, KYH1872 is consisted of a C-terminal fragment of the SelK protein and promiscuous kinase inhibitor YHJ1039 via PGE linker.