E1/E2/E3 Enzyme Degrader

XMU-MP-8 (SKPer1) is a potent molecular glue degrader that targets the oncoprotein SKP2. XMU-MP-8 simultaneously binds to the F-box domain of SKP2 (K_d ≈ 36 μM) and the N-terminal TPR domain of the E3 ligase STUB1 (K_d ≈ 2.5 μM), forming a stable SKP2-SKPer1-STUB1 ternary complex (K_d ≈ 8.9 nM) that induces SKP2 ubiquitination and proteasomal degradation. XMU-MP-8 selectively eliminates SKP2-expressing cancer cells. XMU-MP-8 exhibits substantial tumour suppression with good safety profiles in vivo. XMU-MP-8 can be used for cancer research, such as non-small cell lung adenocarcinoma (NSCLC) and prostatic adenocarcinoma.

CRBN-6-5-5-VHL is a potent and selective VHL E3 ligand-based Cereblon (CRBN) PROTAC degrader with a DC₅₀ value of 1.5 nM. CRBN-6-5-5-VHL forms a heterotrimeric complex with CRBN and VHL E3 ligase, thereby promoting CRBN ubiquitination and proteasomal degradation without inducing VHL degradation. CRBN-6-5-5-VHL protects myeloma from the toxic effects of IMiDs. CRBN-6-5-5-VHL can be used in the research of multiple myeloma.

PROTAC CRBN Degrader-1 (Compound 14a) is a VHL-CRBN heterodimerization PROTAC degrader that achieves a selective degradation of CRBN by binding two E3 ubiquitin ligases (VHL and CRBN) to each other.

MS181 is a BMI1 and RING1B degrader with antiproliferative activity. MS181 induces degradation via an EED-, CRBN-, and ubiquitin-proteosome system-dependent pathway, with preferential targeting over PRC2 components. MS181 acts in VHL-defective cancer cells. MS181 serves as a chemical biology tool to study PRC1 roles in cancer. MS181 can be used for the research of myelogenous leukemia, renal cell carcinoma, metastatic prostate cancer, triple negative breast cancer.

PROTAC SKP2 Degrader-1 is a PROTAC degrader targeting SKP2, with a K_d value of 6.28 μM. PROTAC SKP2 Degrader-1 induces targeted degradation of SKP2 via the ubiquitin-proteasome system. PROTAC SKP2 Degrader-1 stabilizes the expression of SOCS1 and regulates the expression of immunoproteasomes through the JAK/STAT pathway, thereby inhibiting tumor cell proliferation. PROTAC SKP2 Degrader-1 is applicable for cancer-related research.

RNF5-IN-1 is a selective small-molecule inhibitor and degrader of the E3 ubiquitin ligase RNF5. RNF5-IN-1 directly binds to the N-terminal cytosolic domain of RNF5 with a K_D of 594 nM, inhibits the E3 ubiquitin ligase activity of RNF5, and exhibits selectivity over Hrd1 and Praja1. RNF5-IN-1 promotes the degradation of RNF5 via the p97/VCP-dependent endoplasmic reticulum-associated degradation (ERAD) and proteasome pathway. RNF5-IN-1 inhibits the retrotranslocation of misfolded proteins. RNF5-IN-1 is applicable for research on mechanisms related to cystic fibrosis.

PROTAC RNF4 degrader-1 is a RNF4 PROTAC degrader (K_d = 64.5 nM) that degrades RNF4 via the ubiquitin-proteasome system. PROTAC RNF4 degrader-1 induces DNA damage, apoptosis, and exhibits antiproliferative activity in cancer cells. PROTAC RNF4 degrader-1 displays antitumor activity with no obvious side effects in mouse models. PROTAC RNF4 degrader-1 is applicable to the research of hepatocellular carcinoma.

MRT-31619 is a selective CRBN Molecular glue degrader, with an IC₅₀ of 14 nM and an EC₅₀ of 72 nM. MRT-31619 triggers ubiquitination and proteasomal degradation of CRBN. MRT-31619 serves as a chemical knockout tool for CRBN depletion to evaluate the dependence of other molecular glues on CRBN. MRT-31619 is applicable to the research of CRBN-related disease models.

PROTAC BET Degrader-13 is a BET PROTAC degrader that recruits TRIM21. PROTAC BET Degrader-13 utilizes wild-type TRIM21 to mediate the degradation of PML-eGFP-BRD4 (BD2) fusion protein aggregates, with an EC₅₀ of 1.4 μM in A549 cells expressing TRIM21-FLAG. PROTAC BET Degrader-13 can be used for research on targeted protein degradation and protein aggregate clearance.

Cbl-b-IN-21 is a PROTAC target protein ligand (Ligands for Target Protein for PROTACs). Cbl-b-IN-21 can be used for synthesis PROTAC Cbl-b-IN-1 (HY-159608).

PROTAC Cbl-b-IN-1 (compound 64) is a potent Cbl-b PROTAC degrader with a DC₅₀ of less than 30 nM. PROTAC Cbl-b-IN-1 can be used for cancer research.

Americanin A is a Neolignan. Americanin A can be isolated from the seeds of Phytolacca americana. Americanin A activates ATM and ATR, initiating the subsequent signal transduction cascades that include Chk1, Chk2, and tumor suppressor p53. Americanin A targets selectively Skp2 for degradation and thereby stabilizes p27. Americanin A suppresses the activity of Cyclin B1 and its partner cdc2 to prevent entry into Mitosis. Americanin A induces Apoptosis by producing excessive ROS. Americanin A has anti-cancer activity against colorectal cancer.

MRT-31619 formate is a molecular gel degrader (MGD) targeting CRBN. MRT-31619 formate drives the self-dimerization of the E3 ligase by mimicking the degradation subunit, and promotes its rapid, effective and selective degradation through the ubiquitin-proteasome system.