ikzf3 degrader

CFT7455 (Cemsidomide) is an anti-cancer agent showing high affinity to the cereblon E3 ligase with a Kd of 0.9 nM. CFT7455 is an orally active degrader of zinc finger transcription factors Ikaros (IKZF1), and Aiolos (IKZF3).

PROTAC CARM1/IKZF3 degrader-1 (Compound 074) inhibits CARM1, reducing the methylation level of its substrate BAF155. This PROTAC degrader works by degrading IKZF 1/3 via a CRBN-dependent mechanism. It suppresses MYC protein expression, thereby inhibiting the proliferation of various multiple myeloma cells. Additionally, PROTAC CARM1/IKZF3 degrader-1 can induce apoptosis in H929 cells and overcomes resistance to immunomodulatory drugs (IMiDs, such as pomalidomide). It is applicable for cancer and immunology research. (Pink: ligand for target protein CARM1/IKZF3 ligand 1; Active form of target protein ligand: EZM 2302; Black: linker; Blue: ligand for E3 ligase Cereblon Thalidomide 4-fluoride)

IKZF3 Degrader 1 (compound 19a) acts as an effective IKZF3 degrader with an EC50 of 0.012 μM and a minimal yield of 9.2%. It enhances the association of IKZF3 with Cereblon (CRBN), subsequently facilitating the ubiquitination and degradation of IKZF3.

Homo-PROTAC cereblon degrader 1 is a highly potent and efficient cereblon (CRBN) degrader with only minimal effects on IKZF1 and IKZF3.

MGD-28 is a potent, orally active Cullin-CRBN-dependent IKZF family protein degrader that dose-dependently degrades IKZF1 (Ikaros), IKZF2 (Helios), and IKZF3 (Aiolos) at nanomolar strengths.MGD-28 also degrades CK1α, and has shown antiproliferative activity against a variety of hematologic cancer cell lines showing antiproliferative activity in vitro and antitumor effects in in vivo assays, and is commonly used in multiple myeloma (MM) and hematological disorders.

MGD-4 is an orally active, Cereblon (CRBN)-dependent degrader of IKAROS proteins that demonstrates dose-dependent degradation of IKZF1 (DC50=67.2 nM), IKZF2 (DC50=918.2 nM), and IKZF3 (DC50=95.8 nM). The compound effectively inhibits the growth of multiple myeloma.

MS40 is a WDR5 PROTAC that selectively degrades WDR5 and serves as a novel degrader for immune-modulating compounds (IMiDs), including the new substrates CRBN and Ikaros zinc finger (IKZF) transcription factors IKZF1 and IKZF3. MS40 facilitates the degradation of WDR5, resulting in the dissociation of the MLL/KMT2A complex from chromatin, thereby reducing H3K4me2 levels. In vitro, MS40 inhibits the growth of primary leukemia patient cells, and in vivo, it suppresses the expansion of patient-derived xenografts.

Thalidomide-NH-C4-Boc is a compound that acts as a ligand and linker for the E3 ligase (Cereblon). It is utilized in the synthesis of PROTAC CARM1/IKZF3 degrader-1.

CARM1/IKZF3 ligand 1 functions as an inhibitor of CARM1 and serves as a target protein ligand for the synthesis of PROTAC CARM1/IKZF3 degrader-1.

Tert-Butyl 6-aminocaproate (Tert-butyl 6-aminohexanoate) is a PROTAC linker. It is utilized in the synthesis of the PROTAC CARM1/IKZF3 degrader-1.

IKZF2-degrader 2 is a selective, orally active molecular glue degrader for IKZF2, with DC50 values of 0.5 nM (HiBit) and 1.8 nM (FACS). It facilitates ubiquitination and degradation of target proteins by recruiting the CRL4-CRBN E3 ubiquitin ligase. IKZF2-degrader 2 shows moderate degradation activity against SALL4 (DC50 of 9 nM) but does not significantly degrade IKZF1, IKZF3, CK1α, or GSPT1. This compound is suitable for research in cancer immunology.

DIX-01 is a molecular glue degrader that simultaneously induces CRBN-mediated degradation of IKZF1/3 and GSPT1, with DC50 values of 19.80 nM for IKZF1, 45.31 nM for IKZF3, and 120.1 nM for GSPT1. It exhibits potent nanomolar antiproliferative activity across various cancer cell lines. Additionally, DIX-01 induces apoptosis in MV4-11 cells and significantly inhibits the growth of leukemia cells in zebrafish models. This compound is utilized in the study of malignant hematological tumors.

Zomiradomide is a PROTAC degradation agent targeting IRAK4, with oral bioavailability, and can also degrade Ikaros (IKZF1) and Aiolos (IKZF3), thereby inhibiting the NF-κB signalling pathway and activating the type I interferon signalling pathway, exhibiting anticancer activity against B-cell lymphoma.