Histone Methyltransferase Degrader

CM112 is a hydrophobic tag-based PRMT1 degrader (DC₅₀ = 0.83 μM) with pan-inhibitory activity against type I PRMTs. CM112 induces proteasome-dependent degradation of PRMT1, inhibits the methyltransferase activities of PRMT1, PRMT3, PRMT4 and PRMT6, downregulates the stability of orphan receptor TR3, thereby interfering with the non-enzymatic scaffolding function of PRMT1. CM112 suppresses clonogenicity and proliferation of tumor cells. CM112 is applicable to research related to breast cancer and non-small cell lung cancer.

SKLB-0124 is a selective PRMT6 degrader based on a hydrophobic labeling (HyT) method. SKLB-0124 is a selective PRMT6 degrader with DC₅₀s of 15.4 μM and a 16.4 μM in HCC827 and MDA-MB-435 cells. SKLB-0124 does not degrade PRMT1 or PRMT8. SKLB-0124 exhibits an IC₅₀ on PRMT6 of 1.6 μM. SKLB-0124 induces proteasome dependent degradation of PRMT6 and significantly inhibits the proliferation. SKLB-0124 effectively induces apoptosis and cell cycle arrest. SKLB-0124 can be used for the studies of lung cancer and breast cancer.

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 G9a degrader-1 is a selective and orally active G9a PROTAC degrader with a DC₅₀ of 1.29 μM. PROTAC G9a degrader-1 inhibits the NF-κB signaling pathway, suppresses the proliferation and migration of cancer cells, promotes apoptosis and cell cycle arrest, and reduces the expression level of H3K9me2. In in vivo models, PROTAC G9a degrader-1 alleviates skin inflammation, reduces epidermal hyperplasia, and decreases Ki67 expression. PROTAC G9a degrader-1 can be used for the research of triple-negative breast cancer and psoriasis.

IHMT-EZH2-426 is an orally active and selective EZH2 degrader. IHMT-EZH2-426 forms a covalent bond with Cys663 of EZH2, inhibits its catalytic activity, and reduces the protein levels of EZH2 as well as the level of H3K27me3. IHMT-EZH2-426 acts as an antiproliferative agent against B-cell lymphoma and triple-negative breast cancer cells, and also exhibits anti-tumor related activity in Pfeiffer and MDA‑MB‑231 xenograft models. IHMT-EZH2-426 can be used in studies related to B-cell lymphoma and triple-negative breast cancer.

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 NSD2 degrader-1 is a PROTAC degrader that selectively targets NSD2, with a DC₅₀ of 0.37 μM. PROTAC NSD2 degrader-1 induces selective degradation of long and short isoforms of NSD2 containing the PWWP1 domain by forming a ternary complex with FBXO22. NSD2 degradation mediated by PROTAC NSD2 degrader-1 depends on the ubiquitin-proteasome system and the neddylation pathway. PROTAC NSD2 degrader-1 can be used in cancer-related research such as non-small cell lung cancer, multiple myeloma and prostate cancer.

RAPRMT5 is a PRMT5 CAP-TAC (proteinase complex-targeted chimeric agent) degrader. RAPRMT5 can induce PRMT5 to undergo proteasome-dependent, ubiquitin-independent degradation. RAPRMT5 can be used in the research of various cancers.

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.

PROTAC EZH2 Degrader-38 (Compound 17) is a EZH2 PROTAC degrader with an IC₅₀ of 165.00 nM. PROTAC EZH2 Degrader-38 functionally inhibits the methyltransferase activity of EZH2 and competitively binds to the SAM-binding pocket of the EZH2 SET domain.

PROTAC EZH2 Degrader-3 is a EZH2 PROTAC degrader. PROTAC EZH2 Degrader-3 induces the global degradation of the PRC2 complex (including EZH2, SUZ12, EED, RbAp48) via the ubiquitin-proteasome pathway and downregulates H3K27me3 levels. PROTAC EZH2 Degrader-3 inhibits cancer cell proliferation and induces their apoptosis. PROTAC EZH2 Degrader-3 can be used in research related to lymphoblastoma and diffuse large B-cell lymphoma.

PROTAC EZH2 Degrader-9 is orally active EZH2 PROTAC degrader degrading EZH2 via the ubiquitin-proteasome pathway. PROTAC EZH2 Degrader-9 downregulates PRC2 core subunits and potent inhibition of H3K27me3 without affecting common CRBN neosubstrates while it was selective over GSp'T1 and ikZF1/3. PROTAC EZH2 Degrader-9 exhibits potent antiproliferative activity against multiple cancer cell lines by inducing cell cycle and apoptosis. PROTAC EZH2 Degrader-9 reverses PRC2-mediated gene silencing and inhibiting EZH2 non-catalytic target gene activation. PROTAC EZH2 Degrader-9 can be used for leukemia, lymphoma, and non-small cell lung cancer research.

PROTAC EZH2 Degrader-26 (compound 11) is an EZH2 degrader developed based on PROTAC technology. PROTAC EZH2 Degrader-26 has an IC₅₀ of 5.80 nM against EZH2. PROTAC EZH2 Degrader-26 exhibits micromolar-level enzyme inhibitory activity against EZH1, with an EZH1 IC₅₀ of 0.06 μM.

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.