ubiquitination in 1

Ubiquitination-IN-1 is an inhibitor of ubiquitination and Cksl-Skp2 protein-protein interaction (IC50: 0.17 μM).

HM90822 is a novel synthetic apoptotic protein (IAP) antagonist that induces apoptosis in human pancreatic cancer cells through proteasome-dependent degradation of IAPs containing the BIR2/3 structural domain.HM90822 inhibits the expression of XIAP and cIAP1/2 proteins in HM822-sensitive Panc-1 and BxPC-3 cells, induces ubiquitylation of IAPs and promotes induces IAP ubiquitination and promotes proteasome-dependent IAP degradation.

Smurf1-IN-A01 (A01) is a ubiquitin ligase Smad ubiquitination regulatory factor-1 inhibitor (Kd: 3.664 nM) that enhances BMP-2 responsiveness by preventing Smurf1-mediated Smad1/5 degradation.

β-Naphthoflavone-CH2-OH (β-NF-CH2-OH) serves as an AhR E3 ligase ligand, forming chimeric molecules when connected to a protein ligand through a linker, resulting in PROTACs or SNIPERs (e.g., β-naphthoflavone-JQ1). These chimeric molecules recruit the AhR E3 ligase complex by incorporating AhR ligands. By inducing ubiquitination-mediated degradation, PROTACs effectively target and degrade cancer-promoting proteins [1].

E3 ligase Ligand 10 serves as a ligand for E3 ubiquitin ligase and can be conjugated to a protein ligand through a linker, resulting in the formation of PROTACs. These PROTACs act as inducers of ubiquitination-mediated degradation, specifically targeting cancer-promoting proteins[1].

E3 ligase Ligand 18 is a small molecule ligand that specifically binds to E3 ubiquitin ligase, and E3 ligase Ligand 18 can be chemically linked to a protein-targeting ligand through a molecular linker to construct proteolysis-targeting chimeras (PROTACs), which subsequently induce ubiquitination-mediated degradation of disease-related proteins such as oncogenic factors, thereby supporting the study of targeted protein degradation in cancer biology.

XMU-MP-9, a bifunctional compound, targets the C2 domain of Nedd4-1 and the allosteric site of K-Ras. It enhances the interaction and induces conformational changes within the Nedd4-1/K-Ras complex. Furthermore, XMU-MP-9 facilitates the ubiquitination and degradation of various K-Ras mutants and inhibits the proliferation of cells with these mutants. This compound is useful in cancer research.

JCS-1 is a potent DcpSPROTAC degrader. It non-covalently binds to DcpS via an RG3039-based warhead and recruits the E3 ligase VHL. JCS-1 facilitates the ubiquitination and degradation of DcpS at nanomolar concentrations, with a DC50 of 87 nM in MOLM-14 cells. This compound can be utilized in research on acute myeloid leukemia and other DcpS-dependent genetic disorders.

RNF5 agonist 1 (analog-1), a structural analog of the RNF5 inhibitor inh-02, is a potent RNF5 agonist. In CFBE41o- cells expressing F508del-CFTR, RNF5 agonist 1 enhances the ubiquitination of ATG4B.

PROTAC HDAC6 degrader 2 (Compound 1) is an HDAC6 PROTAC degrader with an IC50 value of 0.643 μM. It facilitates the ubiquitination and degradation of HDAC6 and is applicable in research on hematological and solid cancers.

HDAC-IN-85 (Compound 1) is an HDAC inhibitor capable of crossing the blood-brain barrier. It exhibits inhibitory effects on brain tumor cell lines and can induce acetylation, resulting in DNA double-strand breaks and promoting RAD51 ubiquitination, which disrupts the DNA repair process. HDAC-IN-85 is applicable in studies of glioblastoma.

PROTACc-Met degrader-3 (Compound 22b) is a c-Met PROTAC degrader. It facilitates the ubiquitination and degradation of c-Met, with a DC50 of 0.59 nM in EBC-1 cells. PROTACc-Met degrader-3 is applicable in lung cancer research.

(S,R,S)-AHPC-Boc derivative 1 (Compound 80-9; VH032-Boc derivative 1) is a selective proteasomal degrader targeting MALT1, which recruits the E3 ubiquitin ligase CRBN to form a ternary complex with MALT1. This interaction leads to the ubiquitination and subsequent proteasomal degradation of MALT1. By disrupting the CBM complex, (S,R,S)-AHPC-Boc derivative 1 inhibits the NF-κB signaling pathway and shows potential in inducing apoptosis in ABC-DLBCL cells. It holds promise for research into MALT1-dependent cancers, such as diffuse large B-cell lymphoma (DLBCL).

HEMTACWEE1degrader-1 is a WEE1-targeting heterobifunctional chimeric degrader (HEMTAC) facilitated by HSP90, exhibiting an HSP90 enzyme inhibitory activity with an IC50 of 16.76 nM. It enhances the ubiquitination and subsequent degradation of WEE1, effectively blocking the G2/M cell cycle transition. This compound shows anticancer properties in patient-derived xenograft (PDX) models of acute myeloid leukemia (AML). HEMTACWEE1degrader-1 is utilized in AML research.

MS2133 is a DOT1L PROTAC degrader. It facilitates the ubiquitination and degradation of DOT1L in THP-1 and MV4-11 cells, with DC50 values of 56 nM and 25 nM, respectively, and reduces H3K79 methylation. MS2133 also inhibits the growth of MLL-r leukemia cells, demonstrating anticancer activity.

Hdm2 E3ligaseinhibitor 1 (Compound 1) is a reversible inhibitor of Hdm2-mediated p53 protein ubiquitination, with an IC50 of 12.7 μM. It binds to Hdm2, blocking the transfer of ubiquitin catalyzed by Hdm2 from pre-linked Ub-Ubc4 to p53, thereby inhibiting p53 ubiquitination, stabilizing p53 protein in tumor cells, and exerting antitumor activity.

PROTAC JAK2 degrader-1 (Compound 10i) is a JAK2 PROTAC degrader with a DC50 of 27.35 nM against JAK2V617F. It facilitates the ubiquitination and degradation of JAK2. This compound also inhibits the phosphorylation of JAK2, STAT3, and STAT5, and is applicable in the study of myeloproliferative neoplasms.

FC-14369 is a PROTAC degrader targeting the HIV-1Nef protein (HIV-1Nef protein) with a DC50 value of 160 nM. By means of its bifunctional structure, FC-14369 binds to both Nef and Cereblon E3 ubiquitin ligase, facilitating Nef ubiquitination and proteasomal degradation. This action restores the expression of cell surface CD4 and MHC-I, thereby inhibiting HIV-1 replication. FC-14369 is applicable in the study of HIV infection and AIDS.

EN219 is a synthetic recruiter of the E3 ubiquitin ligase RNF114 and binds specifically to cysteine 8 (C8) within its intrinsically disordered region, exhibiting an IC50 of 470 nM. EN219 inhibits RNF114-induced autoubiquitination and p21 ubiquitination in cell-free assays at 50 μM. At 1 μM, EN219 interacts with multiple proteins including the tubulin β1 chain (TUBB1), heat shock protein 60 (Hsp60/HspD1), and histone H3.1 (HIST1H3A) in 231MFP breast cancer cells. Furthermore, EN219 has been linked to the bromodomain inhibitor (+)-JQ1 for the creation of a PROTAC capable of degrading BRD4 in 231MFP cells.

SCH529074 is a selective activator of p53 (Ki = 1 μM) and can be used in studies about non-small-cell lung carcinoma. SCH529074 restores mutant p53 function and interrupts HDM2-mediated ubiquitination of wild Type p53.

PROTAC IDO1 Degrader-1, a pioneering compound, efficiently targets indoleamine 2,3-dioxygenase 1 (IDO1) for ubiquitination and degradation by recruiting IDO1 to the CRBN E3 ligase, thereby facilitating its entry into the ubiquitin-proteasome system (UPS) with a DC50 of 2.84 μM. This compound also moderately enhances the tumor-killing efficacy of HER2 CAR-T cells[1].

HB007 is an effective SUMO1 degradation agent that inhibits tumor growth by inducing SUMO1 ubiquitination and degradation, increasing endoplasmic reticulum (ER) stress and ROS production, suitable for cancer research.

NCT02 is a molecular glue degrader targeting CDK12 and CCNK (cyclin K), inducing CCNK ubiquitination and inhibiting CRC cell proliferation in vivo and in vitro, leading to apoptosis and cell cycle arrest. It is intended for the investigation of metastatic colorectal cancer (CRC).

Nrf2 activator-2 (referred to as compound O15), an Osthole derivative, is a highly potent Nrf2 agonist exhibiting an EC 50 of 2.9 μM in 293 T cells. By effectively disrupting the binding between Keap1 and Nrf2, Nrf2 activator-2 activates the Nrf2 pathway. Furthermore, this compound significantly reduces the ubiquitination of Nrf2 in cells, indicating its potential in regulating Nrf2 activity [1].