E1/E2/E3 Enzyme Degrader

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.

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.

RNF5-IN-1 (FX12) is a selective RNF5 degrader. RNF5-IN-1 binds to RNF5 and inhibits its E3 activity, and promotes proteasomal degradation of RNF5 in an endoplasmic reticulum (ER)-associated degradation (ERAD) way in cells. RNF5-IN-1 inhibits α-1-antitrypsin (NHK) dislocation with an IC₅₀ value of 2.7 μM. RNF5-IN-1 can be used for research of cystic fibrosis, acute myeloid leukemia, and certain viral infections.

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.

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.

JP-2-196 hydrochloride is a covalent molecular glue degrader targeting RNF126. JP-2-196 hydrochloride induces the formation of a ternary complex between RNF126 and target proteins (e.g., BRD4, AR-V7), promoting their ubiquitination and proteasomal degradation. JP-2-196 hydrochloride is promising for research of cancers (e.g., prostate cancer, leukemia).

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.