GPX4 Degrader

PROTAC GPX4 degrader-1 is a glutathione peroxidase 4 (GPX4) PROTAC degrader with a DC₅₀ of 30 nM. PROTAC GPX4 degrader-1 induces ROS accumulation and ferroptosis in cancer cells. PROTAC GPX4 degrader-1 inhibits cell growth and reduces GPX4 levels in tumor tissues. PROTAC GPX4 degrader-1 can be used in research related to various cancers including fibrosarcoma, non-small cell lung cancer, and melanoma.

PROTAC GPX4 degrader-4 is a potent GPX4 PROTAC degrader, with DC₅₀ values of 1366.67 nM and 475.15 nM in T24 and RT4 cells, respectively. PROTAC GPX4 degrader-4 targets and degrades GPX4 protein via the ubiquitin-proteasome system, thereby inducing cellular ferroptosis. PROTAC GPX4 degrader-4 can be used for research on bladder cancer.

PROTAC GPX4 degrader-3 is a glutathione peroxidase 4 (GPX4) PROTAC degrader with a DC₅₀ of 0.019 μM in HT1080 cells. PROTAC GPX4 degrader-3 degrades GPX4 primarily via the ubiquitin-proteasome system (UPS) in a dose- and time-dependent manner. PROTAC GPX4 degrader-3 induces lipid peroxidation (LPO) and ROS accumulation, thereby triggering ferroptosis (ferroptosis). PROTAC GPX4 degrader-3 exhibits in vitro anti-tumor activity against cancer cells. PROTAC GPX4 degrader-3 can be used in the research of fibrosarcoma, triple-negative breast cancer, and renal cell carcinoma.

PROTAC GPX4 degrader-5 (compound N15) is an efficient and highly selective PROTAC GPX4 degrader (DC₅₀ = 28 nM). PROTAC GPX4 degrader-5 can induce ferroptosis and has low toxicity to normal cells. PROTAC GPX4 degrader-5 can significantly increase ROS. PROTAC GPX4 degrader-5 exerts anti proliferative effects on various tumor cells. PROTAC GPX4 degrader-5 is commonly used in cancer research.

GPX4 degrader-1 (Compound RS-1) is a hydrophobic tagging (HyT)-mediated GPX4 degrader (DC₅₀: 8.9 nM in HT1080 cells) GPX4 degrader-1 induces GPX4 degradation. GPX4 degrader-1 induces Ferroptosis. GPX4 degrader-1 increases lipid ROS. GPX4 degrader-1 demonstrates potent antitumor efficacy in a murine mammary carcinoma model.

ZX703 is a GPX4 PROTAC degrader with a DC₅₀ of 0.135 μM. ZX703 degrades GPX4 via the ubiquitin-proteasome and autophagy-lysosome pathways. ZX703 induces the accumulation of ROS, thereby triggering Ferroptosis. ZX703 can be used in studies related to fibrosarcoma and prostate cancer.

NC-R17 is a PROTAC degrader that targets glutathione peroxidase 4 (GPX4) for degradation by recruiting cereblon. With RSL3 as its parent core, NC-R17 binds non-covalently to GPX4. NC-R17 exhibits moderate GPX4 degradation activity in tumor cells and can be used in studies related to ferroptosis (ferroptosis) and tumors.

GDCNF-11 is a type of HSP90 interaction-mediated protein degradation chimera (HIM-PROTAC) degrader that targets and degrades GPX4, with a DC₅₀ of 0.08 μM. GDCNF-11 mediates the ubiquitination and proteasome-dependent degradation of GPX4 by recruiting GPX4 to form a ternary complex with HSP90, increases intracellular lipid peroxides and ROS, and ultimately triggers Ferroptosis. GDCNF-11 inhibits tumor growth in mouse models, downregulates GPX4 protein in xenograft tumors, and upregulates the lipid peroxidation marker. GDCNF-11 can be used for the research of fibrosarcoma.

PROTAC GPX4 degrader-2 is a cIAP-recruiting GPX4 PROTAC degrader with a DC₅₀ of 1.68 μM. PROTAC GPX4 degrader-2 forms a ternary complex with GPX4 and cIAP, and induces GPX4 degradation via the ubiquitin-proteasome system pathway. PROTAC GPX4 degrader-2 induces Mitochondrial depolarization and Ferroptosis. PROTAC GPX4 degrader-2 exhibits antiproliferative effects in cancer cells. PROTAC GPX4 degrader-2 can be used for the research of fibrosarcoma.

USP30-IN-20 is an orally active USP30 inhibitor (K_d = 1.61 μM, IC₅₀ = 12.8 μM). USP30-IN-20 induces ferroptosis by promoting ubiquitination-mediated degradation of GPX4. USP30-IN-20 inhibits the proliferation, migration, invasion, and stemness of prostate cancer cells. USP30-IN-20 induces G0/G1 cell cycle arrest and ROS levels in prostate cancer cells. USP30-IN-20 exhibits significant anti-tumor efficacy in PC3 cell subcutaneous xenografts in mice. USP30-IN-20 can be used for the study of advanced prostate cancer.

GPX4-AUTAC is a GPX4-targeting autophagy-mediated degrader (AUTAC). GPX4-AUTAC consists of an inhibitor ML162-yne (HY-153748), a degradation tag FBnG (HY-W073762) and a glycol linker (HY-W021401). GPX4-AUTAC promotes the ubiquitination of GPX4 by E3 ligase TRAF6, and enhances the binding with GPX4 and p62, leading to the selective autophagy-dependent degradation of GPX4. GPX4-AUTAC significantly induces ferroptosis and shows a potent anti-cancer activity in breast cancer cells, breast cancer-derived organoids (PDOs) and MDA-MB-231 tumor xenograft mice model, with potent synergistic effects when combined with Sulfasalazine (SAS) (HY-14655) or chemotherapy drugs (Paclitaxel (HY-B0015) or Cisplatin (HY-17394)).

MB-Buf is a conjugation of methylene blue (HY-14536) and bufalin (HY-N0877) . MB-Buf can targeting degrade GPX4 upon light activation. MB-Buf can induce cell apoptosis, ferroptosis, and ROS production. MB-Buf can be used for the research of cancer, such as breast cancer.

ZX782 is a HyT GPX4 degrader and a ferroptosis inducer, which induces GPX4 degradation and significantly increases lipid ROS accumulation in HT1080 cells. ZX782 can be used to treat AD by reducing the size and/or number of brain amyloid plaques and by inhibiting the spread of IL-1beta-positive microglial-like cells around amyloid plaques. ZX782 is labeled with hydrophobic benzyl alcohol (HBA) and appears bright blue under acidic conditions, which can be used for quantitative determination. ZX782 is composed of target protein ligand (red part) ML-210 (HY-100003), PROTAC linker (black part) Bromo-PEG2-CH2-Boc (HY-141371) and Hty molecule (blue part) Adamantan-1-ylmethanamine (HY-W037848). The conjugate consisting of Hyt and linker parts is Adamantan-C-amide-PEG2-C-Br (HY-161974), and the activity control of the target protein ligand is Hydroxyl-ML-210 (HY-161973).