GS143 is a selective IκBα ubiquitination inhibitor with an IC50 of 5.2 μM for SCFβTrCP1-mediated IκBα ubiquitylation. GS143 suppresses NF-κB activation and transcription of target genes and does not inhibit proteasome activity. GS143 has anti-asthma effect[1][2].
(Rac)-Nutlin-3 (Rebemadlin), an active enantiomer of Nutlin-3, is a potent murine double minute (MDM2) inhibitor (IC50=90 nM). (Rac)-Nutlin-3 inhibits MDM2-p53 interactions and stabilizes the p53 protein, and induces cell autophagy and apoptosis. (Rac)-Nutlin-3 has the potential for the study of TP53 wild-type ovarian carcinomas[1][2].
PRT4165 is a potent inhibitor of PRC1-mediated H2A ubiquitylation.
VII-31 is a potent NEDDylation pathway activator to inhibit the tumor progression in vitro and in vivo. VII-31 induces apoptosis via intrinsic and extrinsic pathways[1].
DI-591 (DI591) is a potent, selective, cell-permeable inhibitor of the DCN1-UBC12 interaction with Ki of 10-12 nM for human DCN1 and DCN2; displays no affinity against DCN3/4/5 (Ki>10 uM); selectively inhibits neddylation of cullin 3 but has no or minimal effect on neddylation of other cullin family members; accumulates NRF2 protein and its transcriptional activation in cells.
Smurf1-IN-1 is an orally active and selective inhibitor of specific E3 ubiquitin protein ligase 1 (SMURF1) with an IC50 of 92 nM. Smurf1-IN-1 has significant efficacy in rats model of pulmonary hypertension[1].
Skp2 inhibitor 2 (14f) is an inhibitor of F-box protein S-phase kinase-associated protein 2 (Skp2), with an IC50 value of 10.2 μM (Skp2-Cks1). Skp2 is a part of cullin-RING ligases, which recruits and ubiquitinates substrates, involving in proteolytic and non-proteolytic process[1].
WS-383 (WS383) is a highly potent, selective, and cellular active inhibitor of DCN1-UBC12 interaction with IC50 of 11 nM; inhibits Cul3/1 neddylation selectively over other cullins and also induces accumulation of p21, p27 and NRF2; exhibits cellular target engagement to DCN1 in MGC-803 cells, enhances the thermal stability of cellular DCN1 protein even at 1 uM
Ginkgolic Acid is a natural compound with suspected cytotoxic, allergenic, mutagenic and carcinogenic properties, and it can inhibit protein SUMOylation both in vitro and in vivo without affecting in vivo ubiquitination.
Cbl-b-IN-3 (Compound 23) is a casitas B-lineage lymphoma proto-oncogene-b (Cbl-b) inhibitor with an IC50 of < 1 nM. Cbl-b is an E3 ubiquitin ligase that negatively regulates T-cell activation[1].
Homo-PROTAC cereblon degrader 1 (compound 15a) is a highly potent and efficient cereblon (CRBN) degrader with only minimal effects on IKZF1 and IKZF3[1].
DCN1-UBC12-IN-3 is potent and selective DCN1-UBC12 inhibitor with an IC50 of 2.25 nM. Anticardiac fibrotic effect[1].
TAK-981 is a first in class and selective inhibitor of the SUMOylation enzymatic cascade, with potential immune-activating and antineoplastic activities[1][2].
NSC689857 is a potent EGFR and SCFSKP2 inhibitor with an IC50 value of 36 μM for Skp2-Cks1. NSC689857 can inhibit p27 ubiquitylation (IC50=30 μM). NSC689857 has varied activity across cancer types, with more activity against leukemia cell lines than others[1][2].
DCN1-UBC12-IN-2 is a potent and specific DCN1-UBC12 inhibitor (IC50=9.55 nM). DCN1-UBC12-IN-2 could specifically target DCN1-UBC12 interaction and relieve Ang II-induced cardiac fibroblast activation[1].
A small molecule inhibitor of HECT-type ubiquitin ligase with IC50 of 6.8/6.3/6.9 uM for Smurf2/Nedd4/WWP1, respectively; does not block E2 binding but causes a conformational change that results in oxidation of the active site Cys; is active against a range of HECT ligases but does not perturb the ubiquitin system more generally.
UBA5-IN-1 (compound 8.5) is a selective UBA5 inhibitor with an IC50 value of 4.0 μM. UBA5-IN-1 inhibits cell proliferation of Sk-Luci6 cancer cells with high expression levels of UBA5[1].
RB-3, a PRC1 inhibitor, binds to RING1B-BMI1f, with a Kd of 2.8 μM[1].
Hydrocotarnine is a Cbl inhibitor, and results in inflammasome-mediated IL-18 secretion in colitis. Hydrocotarnine increases expression of GLUT1 and cellular glucose uptake in glycolytic metabolism. Hydrocotarnine acts as an agent that provides analgesic effect in cancer research[1][2][3].
Cbl-b-IN-7 (Compound 248) is a casitas B-lineage lymphoma-b (Cbl-b) and c-Cbl inhibitor with IC50s of 6.7 nM and 5.2 nM, respectively[1].
SCFSkp2-IN-2 (Compound AAA-237) is a Skp2 inhibitor with a KD of 28.77 μM. AAA-237 induces apoptosis of NSCLC cells and shows antitumor activities[1].
Skp2 Inhibitor C1(SKPin C1) is a specific small molecule inhibitor of Skp2-mediated p27 degradation, selectively inhibited Skp2-mediated p27 degradation by reducing p27 binding through key compound-receptor contacts.IC50 value: Target: Skp2 inhibitor; p27 regulatorin vitro: T47D cells treated with C1 (5 μM for 16 hours) displayedan increase in G1 phase (p < 0.0001) and a decrease in S phase (p < 0.0001), correlating with p27 protein induction. In contrast, MCF-7 cells responded to C1 with a significant reduction in G1 phase (35%, p < 0.0001) and an increase in G2-M phase (43%, p < 0.0001). This G1 reduction and G2/M arrest is dose dependent on C1 (Figure 5C right; p < 0.001 and p < 0.01, respectively) and correlates with increased p27 protein levels (Figure 5E left, S4A top right) [1].
Cbl-b-IN-6 (Compound 246) is a casitas B-lineage lymphoma-b (Cbl-b) and c-Cbl inhibitor with IC50s of 6.7 nM and 5.2 nM, respectively[1].
p53-MDM2-IN-1 (Example 30) is an inhibitor of p53-MDM2/X protein interaction with an Ki value of 23.35 µM. p53-MDM2-IN-1 can be used for anti-tumor research[1].
SMER3, a Rapamycin enhancer, is a selective Skp1-Cullin-F-box (SCF)Met30 ubiquitin ligase inhibitor. SMER3 enhances Rapamycin's growth inhibitory effect by inhibition of SCFMet30[1].
Thalidomide is initially promoted as a sedative, inhibits ereblon (CRBN), a part of the cullin-4 E3 ubiquitin ligase complex CUL4-RBX1-DDB1, with a Kd of ∼250 nM, and has immunomodulatory, anti-inflammatory and anti-angiogenic cancer properties.
Cbl-b-IN-12 (Example 10) is a casitas B-lineage lymphoma-b (CBL-B) inhibitor with an IC50 of <100 nM[1].
HLI98C is a ubiquitin ligase inhibitor. HLI98C inhibits p53 ubiquitylation. HLI98C inhibits HDM2 auto-ubiquitylation[1].
C25-140, a first-in-class TRAF6-Ubc13 inhibitor, directly binds to TRAF6, thereby blocks the interaction of TRAF6 with Ubc13 and as a consequence lowers TRAF6 activity. C25-140 expands studying the impact of the ubiquitin system on immune signaling and underscores the importance of TRAF6 E3 ligase activity in psoriasis and rheumatoid arthritis (RA)[1].
Ubiquitination-IN-1 (compound 24) is a ubiquitination and Cksl-Skp2 protein-protein interaction (IC50=0.17 μM) inhibitor. Ubiquitination-IN-1 increases levels of p27. Ubiquitination-IN-1 can be used to treat disease by blocking the degradation of tumor suppressors[1].