Histone Methyltransferase Degrader

UNC8153 TFA is a potent and selective nuclear receptor-binding SET domain-containing 2 (NSD2)-targeted degrader with a K_d of 24 nM. UNC8153 TFA reduces the cellular levels of both NSD2 protein (DC₅₀ in cell U2OS is 0.35 μM) and the H3K36me2 chromatin mark. UNC8153 TFA contains a simple warhead that confers proteasome-dependent degradation of NSD2.

UNC8732 is an NSD2 degrader with a K_d value of 76 nM for NSD2, and achieves highly selective degradation of NSD2 across the detectable proteome. UNC8732 acts as a prodrug; its primary amine is metabolized to an aldehyde, which forms a reversible covalent interaction with Cys326 in the FIST_C domain of FBXO22, recruiting the SCF_FBXO22 ubiquitin ligase complex to mediate polyubiquitination and proteasomal degradation of NSD2. UNC8732 serves as a chemical probe to investigate NSD2-associated disease phenotypes and study the functions of NSD2 in nuclear signaling and epigenetics. UNC8732 can be used in studies of acute lymphoblastic leukemia.

EED226-COOH is an EED226-derived ligand for target protein EED ligand for PROTAC, binds to a ligand for VHL via linker to form UNC6852 (HY-130708) to degrade PRC2.

MS159 is a potent nuclear receptor binding SET structural domain protein 2 (NSD2) PROTACdegrader. MS159 inhibits the growth of tumour cells. MS159 is a useful chemical tool for exploring the role of NSD2 in health and disease.

G9D-4 TFA is a G9a PROTAC degrader. G9D-4 TFA induces G9a degradation, reduces H3K9me2 levels, and prevents GLP interference via the CRBN ternary complex, proteasome and ubiquitin-like modification-dependent pathways. G9D-4 TFA exerts antiproliferative activity and induces Apoptosis in pancreatic cancer cells. G9D-4 TFA can be used for research on pancreatic cancer.

UNC8153 is a potent and selective nuclear receptor-binding SET domain-containing 2 (NSD2)-targeted degrader with a K_d of 24 nM. UNC8153 reduces the cellular levels of both NSD2 protein (DC₅₀ in cell U2OS is 0.35 μM) and the H3K36me2 chromatin mark. UNC8153 contains a simple warhead that confers proteasome-dependent degradation of NSD2.

PROTAC BLIMP-1 degrader-1 is an orally active BLIMP-1 PROTAC degrader with an EC₅₀ of 13.1 nM. PROTAC BLIMP-1 degrader-1 recruits the neprilysin (CRBN) E3 ligase to mediate ubiquitination and subsequent degradation of BLIMP-1α via the 26S proteasome, without affecting the BLIMP-1β isoform. PROTAC BLIMP-1 degrader-1 inhibits cancer cell proliferation and tumor growth. It can be used in research related to multiple myeloma.

UNC10088 is a molecular glue targeting NSD2. UNC10088 mediates the formation of a stable ternary complex between SCFFBXO22 and the NSD2 PWWP1 domain. UNC10088 promotes ubiquitination of the SCFFBXO22-dependent NSD2 PWWP1 domain through reversible covalent bonding with the C326 region of FBXO22. UNC10088 could be used in cancer research.

PROTAC EZH2 Degrader-12 (compound 3) is a CRBN-recruiting PROTAC-based EZH2 degrader with an EZH2 IC₅₀ of 3.90 nM and EZH1 IC₅₀ of 5.24 μM.

PROTAC EZH2 Degrader-30 (compound 67) is ais a PROTAC protein degrader targeting EZH2 with an IC₅₀ of 6.22 μM against SU-DHL-6 cells. PROTAC EZH2 Degrader-30 can be used for the research of diffuse large B-cell lymphoma.

PROTAC EZH2 Degrader-17 (compound 52) is a PROTAC protein degrader targeting EZH2 with an antiproliferative IC₅₀ of 18.32 μM in lymphoma cells. PROTAC EZH2 Degrader-17 exhibits antiproliferative activity against lymphoma cells. PROTAC EZH2 Degrader-17 can be used for the research of lymphoma.

WIZ-IN-1 (Example 2) is a Wiz inhibitor (DC₅₀: 0.36 μM). WIZ-IN-1 can be used for research of inherited blood disorders (e.g., hemoglobinopathies, e.g., beta- hemoglobinopathies), such as sickle cell disease and beta-thalassemia.

PROTAC EZH2 Degrader-15 (compound 5) is an EZH2-targeting PROTAC. PROTAC EZH2 Degrader-15 functionally inhibits EZH2 methyltransferase activity.

PROTAC CARM1 degrader-2 is a selective PROTAC-based CARM1 degrader with a DC₅₀ of 8.8 nM in breast cancer cells. PROTAC CARM1 degrader-2 mediates CARM1 protein degradation in a ubiquitin ligase- and proteasome-dependent manner, and reduces the methylation level of downstream substrates of CARM1. PROTAC CARM1 degrader-2 can be used in breast cancer-related research.

PROTAC EZH2 Degrader-10 is a selective PROTAC protein degrader targeting EZH2. PROTAC EZH2 Degrader-10 can be used for the research of cancer.

PROTAC EZH2 Degrader-35 (compound U3i (44)) is a PROTAC protein degrader targeting EZH2 with a human EZH2 K_a of 16.19 nM. PROTAC EZH2 Degrader-35 exhibits antiproliferative activity in triple-negative breast cancer cells and minimal cytotoxicity in normal human epithelial, hepatic, renal cells.PROTAC EZH2 Degrader-35 can be used for the research of triple-negative breast cancer.

ND-L11B is a potent degrader of nuclear receptor binding SET domain protein 2 (NSD2) and RE-IIBP, with the DC₅₀ of 1.48 and 0.8 μM, the D_max is closed to 80 %.

WIZ degrader 1 is a degrader for widely interspaced zinc finger motifs (WIZ) with an AC₅₀ of 2 nM. WIZ degrader 1 induces the expression of fetal hemoglobin (HbF) with an EC₅₀ of 6 mM. WIZ degrader 1 is used in research of inherited blood disorders.

PROTAC EZH2 Degrader-37 (compound 16) is a PROTAC protein degrader targeting EZH2 with a target IC₅₀ of 144 nM. PROTAC EZH2 Degrader-37 is applicable to lymphoma-related research.

PROTAC EZH2 Degrader-28 is an EZH2 PROTAC degrader. PROTAC EZH2 Degrader-28 promotes the ubiquitination and degradation of EZH2. PROTAC EZH2 Degrader-28 can be used for lymphoma-related research.