IKZF Family Degrader

Pomalidomide, the third-generation immunomodulatory agent, acts as molecular glue. Pomalidomide interacts with the E3 ligase cereblon and induces degradation of essential Ikaros transcription factors.

Golcadomide (CC-99282) is a blood-brain barrier-permeable, orally active Cereblon (CRBN) E3 ligase modulator. Golcadomide induces Cereblon to form a closed active conformation, thereby recruiting and triggering the ubiquitin-mediated proteasomal degradation of transcription factors IKZF1, IKZF3, Ikaros and Aiolos. Golcadomide is applicable to research related to relapsed or refractory non-Hodgkin lymphoma, chronic lymphocytic leukemia/small lymphocytic lymphoma, and diffuse large B-cell lymphoma.

Cemsidomide (CFT7455) is a ubiquitin ligase pathway based IKZF1/3 (Ikaros/Aiolos) degrader with molecular glue activity. Cemsidomide has a GI₅₀ of 0.05 nM for NCIH929.1 cells. Cemsidomide is used in the research of multiple myeloma (MM).

FPFT-2216 is an orally active Molecular glue degrader targeting IKZF1, IKZF3, CK-1α, and PDE6D, with a DC₅₀ of 8 nM against PDE6D. FPFT-2216 mediates ubiquitin-proteasome degradation via the CRL4^CRBN E3 ubiquitin ligase complex and interacts with the non-isoprenoid-binding region of PDE6D. FPFT-2216 activates the p53 signaling pathway, inhibits the CBM complex/NF-κB pathway, upregulates IL-2, suppresses IL-1β and IL-6, and induces tumor cell Apoptosis. FPFT-2216 exhibits anticancer activity against multiple myeloma and lymphoma. FPFT-2216 can be used in research related to multiple myeloma, lymphoma, acute lymphoblastic leukemia, acute myeloid leukemia, pancreatic ductal adenocarcinoma, non-small cell lung cancer, and gastric adenocarcinoma.

DEG-77 is a molecular glue targeting IKZF2 and CK1α, with DC₅₀ values of 15.3 nM and 10 nM, respectively. DEG-77 exhibits significant anti-tumor activity, inducing increased transcriptional levels of the pro-apoptotic protein Bax and the cell cycle arrest protein p21. DEG-77 is applicable to the research of acute myeloid leukemia (AmL), diffuse large B-cell lymphoma and ovarian cancer.

PLX-4545 is an orally active, selective molecular glue degrader targeting IKZF2. Through a molecular glue mechanism, PLX-4545 binds to CRBN, recruits IKZF2 to form a ternary complex, and promotes its ubiquitination and proteasomal degradation. This further converts inhibitory regulatory T cells (T_reg) into effector-like T cells, enhances CD8⁺ T cell responses, and modulates the T_eff:T_reg balance. PLX-4545 also increases the production of the inflammatory cytokine IL-2 and reduces the suppressive activity of T_reg. PLX-4545 can be used in cancer immunotherapy research, and exhibits a synergistic effect when combined with immune checkpoint inhibitors such as anti-PD1.

BSJ-02-162 (CDK4/6-IN-11) is a CDK4/CDK6 and IKZF1/IKZF3 degrader, with DC₅₀ values of 32 nM and 6.1 nM against CDK4 and CDK6, respectively; its IC₅₀ ranges from 1 to 50 nM. BSJ-02-162 induces G1-phase cell cycle arrest, reduces phosphorylated retinoblastoma protein levels, and exerts antiproliferative activity in mantle cell lymphoma cells. BSJ-02-162 is applicable to research related to mantle cell lymphoma.

(S,S)-PLX-4545 (Compound I) is an orally active and cereblon-based molecular glue degrader of IKZF2 (zinc finger transcription factor Helios). (S,S)-PLX-4545 can be used for the study of IKZF2-mediated diseases or disorders, such as proliferative diseases or disorders and/or cancer.

Sontigidomide is a protein molecular glue degrader that can effectively degrade IKZF1/3 and GSPT1 proteins. Sontigidomide can be used to study inflammatory and immune system diseases. GSPT1/IKZF1/3 Molecular Glue Degrader

DEG-35 is a CRBN-dependent, dual IKZF2 and CK1α molecule glue degrader, with DC₅₀ values of 1.4 nM and 4.4 nM for CK1α and IKZF2, respectively. DEG-35 activates the p53 apoptosis pathway. DEG-35 can be used in the research for Acute Myeloid Leukemia (AML).

GSPT1 degrader-19 is a molecular glue degrader targeting GSPT1, IKZF1 and IKZF3, with DC₅₀ values of 0.88 nM, 11.54 nM and 13.84 nM, respectively, in MM.1S multiple myeloma cells. GSPT1 degrader-19 induces cereblon (CRBN)-dependent ubiquitination and proteasomal degradation of IKZF1, IKZF3, GSPT1 and GSPT2, and also reduces ZFP91 protein levels via a CRBN-dependent pathway. GSPT1 degrader-19 exerts antiproliferative effects on cancer cells, induces global proteomic changes including downregulation of novel substrates, and exhibits activity against multiple myeloma and leukemia cell lines. GSPT1 degrader-19 can be used in research related to multiple myeloma and leukemia.

(R)-Zelebrudomide ((R)-NX-2127) is an isomer of Zelebrudomide (HY-153220). Zelebrudomide is an orally active BTK-targeting PROTAC degrader, with DC₅₀ values of 4.5 nM and 31 nM against wild-type BTK and BTK^C481S mutant, respectively. Zelebrudomide recruits the cereblon E3 ubiquitin ligase complex to mediate the degradation of BTK. Zelebrudomide also acts as a molecular glue to bind the cereblon E3 ubiquitin ligase complex, mediating the degradation of IKZF1 and IKZF3. Zelebrudomide can be used in the research of B-cell malignancies.

MGD-28 is a potent, orally active, Cereblon (CRBN)-dependent IKAROS protein degrader that degrades IKZF1 (DC₅₀=3.8 nM), IKZF2 (DC₅₀=56.3 nM), and IKZF3 (DC₅₀=7.1 nM) in a dose-dependent manner. In addition, MGD-4 also degrades CK1α (DC₅₀=7.8 nM). MGD-28 has antiproliferative activity and can be used in multiple myeloma research.

PVTX-405 is a selective and oral active IKZF2 molecular glue degrader with a DC₅₀  of  0.7 nM and a D_max of 91%. PVTX-405 enhances degradation efficiency, significantly reduces off-target degradation, and alleviates hERG inhibition with IC₅₀ of 48 µM. PVTX-405 significantly inhibits the growth of MC38 tumors, with greater synergistic anti-cancer efficacy in combination with immune checkpoint therapies (ICTs) (anti-PD1 or anti-LAG3) in the MC38 mouse tumor xenograft model using Crbn^391V C57BL/6 mice.

FIZ1 degrader 1 is an IMiD-based molecular glue degrader. FIZ1 degrader 1 induces CRBN-dependent FIZ1 ubiquitination and proteasomal degradation; inhibition of the proteasome, ubiquitination or ubiquitination-like processes blocks this degradation. FIZ1 degrader 1 also induces the degradation of IKZF1, IKZF3 and ZFP91. FIZ1 degrader 1 is applicable to molecular glue-related research.

(1S,2S,3R)-PLX-4545 is the (1S,2S,3R) enantiomer of PLX-4545 (HY-159647). PLX-4545 is an orally active and selective cereblon-based molecular glue degrader of IKZF2 (zinc finger transcription factor Helios). PLX-4545 can reprogram immunosuppressive regulatory T cells into pro-inflammatory effector T cells, thereby enhancing anti-tumor immune responses.

3-Chlorobenzaldehyde (m-Chlorobenzenecarboxaldehyde) is a kind of biological materials or organic compounds that are widely used in life science research.

BMS-986482 is a CRBN-mediated IKZF1-4 (Ikaros family zinc finger 1-4) molecular glue degrader. BMS-986482's activity is driven by a non-traditional CELMoD core that selectively degrades the IKZF protein family. BMS-986482 can be used for the research of advanced solid tumors.

MGD-4 is an orally active, Cereblon (CRBN)-dependent IKAROS protein degrader that degrades IKZF1 (DC₅₀=67.2 nM), IKZF2 (DC₅₀=918.2 nM), and IKZF3 (DC₅₀=95.8 nM) in a dose-dependent manner. MGD-4 effectively inhibits the growth of multiple myeloma.

BMS-986482 acetate is a CRBN-mediated IKZF1-4 (Ikaros family zinc finger 1-4) molecular glue degrader. BMS-986482 acetate's activity is driven by a non-traditional CELMoD core that selectively degrades the IKZF protein family. BMS-986482 acetate can be used for the research of advanced solid tumors.