IKZF

NX-2127 (ETX2514 Triethylamine) is an orally active BTK inhibitor that induces degradation of mutant BTKC481S in cells.NX-2127 has potent antiproliferative activity and inhibits the proliferation of BTKC481S mutant TMD8 cells.NX-2127 potently catalyzes the degradation of Ikaros (IKZF1) and Aiolos (IKZF3) at 25 nM and 54 nM, respectively. NX-2127 is associated with the immune system, stimulating T cell activation and increasing IL-2 production in primary human T cells.

Lenalidomide (CC-5013) is an immunomodulator with oral activity. Lenalidomide is a ligand for the ubiquitin E3 ligase cereblon (CRBN), which selectively ubiquitinates and degrades two lymphoid transcription factors, IKZF1 and IKZF3, via the CRBN-CRL4 ubiquitin ligase, and is commonly used in the synthesis of PROTAC products.

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).

NVP-DKY709 is a potent inhibitor of IKZF2 for the treatment of cancers.

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

GATA4-NKX2-5-IN-1 exhibits no activity on the protein kinases involved in the regulation of GATA4 phosphorylation, and it modulates the hypertrophic agonist-induced cardiac gene expression.GATA4-NKX2-5-IN-1  dose-dependently inhibits the GATA4–NKX2-5 tran

Lenalidomide hemihydrate is a derivative of Thalidomide, an orally active immunomodulator that acts as a molecular gel. It is a ligand for the ubiquitin E3 ligase cereblon, which selectively ubiquitinates and degrades two lymphoid transcription factors, IKZF1 and IKZF3, via the CRBN-CRL4 ubiquitin ligase.

FPFT-2216 is a molecular gel that degrades IKZF6, IKZF1, DE1D, and CK3α.FPFT-2216 has potential antitumor activity and can be used to study diseases of the immune system.FPFT-2216 is a molecular gel that degrades IKZF6, IKZF1, DE1D, and CK3α.

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.

TL4-12 is a specific MAP4K2/GCK inhibitor that inhibits IKZF1 and BCL-6.TL4-12 inhibits MM cell proliferation and induces apoptosis, and can be used in the study of multiple myeloma (MM).

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.

BMS-986449 is a CELMoD-type molecular gel that remodels the function of regulatory T cells (Treg) and enhances their anti-tumor immune responses by directing the E3 ubiquitin ligase, Cereblon, to target the degradation of IKZF2 (Helios) and IKZF4 (Eos). BMS-986449 has potential application in the study of advanced solid tumors.

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)

IKZF2-degrader 1 (Compound 31) is a molecular glue-type degrader of IKZF2 with a DC50 of 0.5 nM. It exhibits relatively low degradation activity against CK1α, with a DC50 of 210 nM. This compound is applicable in research focused on IKZF2-dependent cancers.

Cisd2 agonist 2 (compound 6), with an EC50 of 191 nM, is an orally active activator of Cisd2, a protein whose levels are associated with nonalcoholic fatty liver disease (NAFLD). In vivo studies have demonstrated that Cisd2 agonist 2 exhibits no significant toxicity in heterozygous hepatocyte-specific Cisd2 knockout (Cisd2hKO-het) mice [1].

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.

IKZF1-degrader-2 (Compound 3), an IKZF1 degrader, exhibits anticancer activity and low toxicity [1].

DEG-35 is a CRBN-dependent bifunctional degrader targeting IKZF2 and CK1α, with DC50 values of 1.4 nM and 4.4 nM for CK1α and IKZF2, respectively. It activates the p53 apoptotic pathway and is applicable for research related to acute myeloid leukemia (AML).

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.

IKZF1-degrader-1 (Compound 9-B) serves as a potent degrader of the IKZF1 protein, exhibiting a DC50 of 0.134 nM. It is applicable in the degradation of tumors [1].

ALV1 is a potent degradation agent of Ikaros and Helios, with similar degradation activity against IKZF1/2/3. ALV1 significantly reduced the protein abundance of IKZF1-4, CK1α (casein kinase 1α, CSNK1A1) and ribosomal protein RPL4, and induced Helios/CRBN dimerization, which promoted IL-2 secretion.

IKZF-IN-1 (Compound I) is a molecular glue that degrades the karos zinc finger family proteins (IKZF) IKZF 1/2/3/4 and is used as an immune modulator in cancer and viral infection research.