Proteasome-IN-1

Proteasome-IN-1 is an inhibitor of proteasome.

PARP-1/Proteasome-IN-1 (compound 42i) is a dual inhibitor of PARP-1 and the proteasome, demonstrating significant inhibitory effects on breast cancer. By downregulating the expression of BRCA1 and RAD51, it impairs homologous recombination repair and induces apoptosis (cellular death).

Proteasome β2c/i-IN-1 (compound 37) is a selective inhibitor of the β2c and β2i subunits of the human proteasome [1].

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.

RN-18 antagonizes Vif function and inhibits HIV-1 replication only in the presence of A3G. RN-18 increases cellular A3G levels in a Vif-dependent manner and increases A3G incorporation into virions without inhibiting general proteasome-mediated protein degradation. RN-18 enhances Vif degradation only in the presence of A3G, reduces viral infectivity by increasing A3G incorporation into virions and enhances cytidine deamination of the viral genome.

Radicicol (Monorden) is an antifungal antibiotic and a potent inhibitor of heat shock protein 90 (Hsp90), which leads to the degradation of Hsp90 by the proteasome by binding to its ATP-binding pocket. In addition, Radicicol inhibits the growth and proliferation of several tumor cell lines. It also has anti-malarial activity and acts as an inhibitor of adipose- and obesity-related proteins (FTO). Radicicol inhibits iNOS gene expression by blocking the p38 kinase signaling pathway and NF-kB/Rel

Rpn11-IN-1 is an effective and selective inhibitor of proteasome subunit Rpn11 (IC50: 390 nM).

SPDP-C6-NHS ester is an alkyl/ether-based linker used in the synthesis of PROTACs. PROTAC molecules contain two ligands joined by a linker: one ligand recruits an E3 ubiquitin ligase and the other binds to a target protein. SPDP-C6-NHS ester enables selective degradation of target proteins by exploiting the ubiquitin-proteasome system.

Boc-C1-PEG3-C4-OBn (PROTAC Linker 15) is a PEG-based PROTAC linker used in the synthesis of various PROTACs, including PROTAC SGK3 degrader-1. PROTACs consist of two distinct ligands connected by a linker; one ligand binds to an E3 ubiquitin ligase, while the other specifically interacts with the target protein, enabling selective degradation of target proteins via the intracellular ubiquitin-proteasome system[1].

Boc-C1-PEG3-C4-OH is an Alkyl/ether-based PROTAC linker used in the synthesis of PROTACs, characterized by their structure of two distinct ligands tethered by a linker, with one ligand binding to an E3 ubiquitin ligase and the other to the target protein, facilitating targeted protein degradation through the ubiquitin-proteasome system [1].

Phthalimide-PEG3-C2-OTs (Compound 5) is a PROTAC linker composed of PEGs, utilized in the synthesis of various PROTACs that connect two distinct ligands through a linker. One ligand targets an E3 ubiquitin ligase, while the other targets the specific protein of interest, enabling selective protein degradation through the ubiquitin-proteasome system [1].

Phthalimide-PEG4-MPDM-OH, a PROTAC linker with a PEGs composition, has applications in the synthesis of various PROTACs. These PROTACs consist of a linker connecting two distinct ligands: one binds to an E3 ubiquitin ligase, while the other binds to the target protein. By leveraging the intracellular ubiquitin-proteasome system, PROTACs selectively induce the degradation of target proteins [1].

Phthalimide-PEG4-PDM-OTBS is a PROTAC linker comprised of polyethylene glycols (PEGs) utilized in the synthesis of various PROTACs, which consist of two distinct ligands connected by a linker: one ligand binds to an E3 ubiquitin ligase, and the other binds to the target protein, leveraging the intracellular ubiquitin-proteasome system to selectively degrade target proteins [1].

(±)15-HETE is an eicosanoid compound that possesses intrinsic biological activities and serves as a key enzymatic precursor for the biosynthesis of numerous other biologically active lipid-derived derivatives; furthermore, this alkyl chain-based structure functions as a proteolysis-targeting chimera (PROTAC) linker utilized in the chemical synthesis of various PROTAC molecules designed for targeted protein degradation.

PROTAC 20S proteasome subunit β5 degrader 1 (compound 12f) serves as a targeted degrader of the 20S proteasome subunit β5, exhibiting a DC50 value of 0.11 μM in FaDu cells. This compound disrupts the cell cycle and promotes apoptosis (apoptosis), while inhibiting cell proliferation and migration in both FaDu and KM3/BTZ cells. It is applicable for research into resistance to Bortezomib in pharyngeal carcinoma and multiple myeloma.

PROTAC TRIB2 degrader-1 (Compound 5k) is a potent TRIB2 degrader that selectively induces TRIB2 degradation via the CRBN-dependent ubiquitin-proteasome pathway. It effectively inhibits cell proliferation and induces cell apoptosis (apoptosis), making it useful in cancer research.

TrxR/EGFR-IN-1 (Compound L1Au2) is a TrxR/EGFR inhibitor with activity against both gefitinib-sensitive and -resistant lung cancer, effectively suppressing tumor proliferation and promoting apoptosis. It enhances GPX4 degradation through autophagosome-lysosome and proteasome pathways, leading to ferroptosis. Additionally, it induces endoplasmic reticulum stress and triggers immunogenic cell death, making it applicable for studies on gefitinib-resistant lung cancer.

MS9024 is a degrader of DNA methyltransferase 1 (DNMT1), facilitating its degradation in HCT116 cells via the ubiquitin-proteasome pathway, with a DC50 of 35 nM (DC50 values are 254 nM in MDA-MB-468 and 101 nM in H1299). Additionally, MS9024 inhibits DNMT1 with an IC50 of 0.43 μM.

c-Met degrader-1 (Compound H11) is an orally active c-Met degrader that operates via the ubiquitin-proteasome system. It exhibits anti-hepatocellular carcinoma (HCC) activity and hampers tumor growth in MHCC97H xenografts. Additionally, c-Met degrader-1 suppresses the proliferation of HCC cells, disrupts the cell cycle, and induces apoptosis. It may also potentially overcome resistance to Type I c-Met inhibitors.

KMS99220 is an orally active Keap-1 activator that acts as an Nrf2 inhibitor protein. It enhances Nrf2 nuclear translocation, increases the expression of antioxidant enzymes (such as heme oxygenase-1) and proteasome subunit genes, and alleviates oxidative stress and protein aggregation damage. KMS99220 is applicable for research in Parkinson's disease (PD).

PROTACERK5 degrader-1 (compound 2) is a bifunctional ERK5 PROTAC degrader. It induces the degradation of ERK5 in MOLT-4 cells via a VHL-mediated proteasome pathway. PROTACERK5 degrader-1 is useful for studying diseases or disorders characterized by abnormal ERK5 activity.

CH091138 is a potent and selective KRASG12D PROTAC degrader, exhibiting a DC50 value of 148.3 nM in HeLa cells and 469.8 nM in AsPC-1 cells. It selectively targets both exogenous and endogenous KRASG12D through the VHL-mediated ubiquitin-proteasome system, without affecting KRASWT or other KRAS mutants (G12C/G12S/G12V). CH091138 demonstrates significant antitumor activity by inducing apoptosis (apoptosis) in tumor cells and is applicable for research in pancreatic and colon cancers.

SF-9-2 is a PD-L1/PD-1 binding inhibitor with an IC50 of 24.9 nM. It suppresses epithelial-mesenchymal transition, migration, invasion, and proliferation of SK-N-SH cells, while also inducing apoptosis and causing cell cycle arrest. SF-9-2 blocks PD-L1-induced growth of SK-N-SH cells via the MAPK signaling pathway. It restores GSK-3β activity and enhances PD-L1 degradation through the ubiquitin-proteasome pathway. In the SK-N-SH NOG mouse model, SF-9-2 inhibits tumor growth without notable toxicity. Additionally, SF-9-2 acts as an immune checkpoint inhibitor, blocking PD-L1 to restore T cell function and is applicable to neuroblastoma research.

1. Steviol (NSC-226902), a natural sweetener, it inhibits proliferation of the gastrointestinal cancer cells intensively. 2. Steviol can induce a significant increase in CYP3A29 expression. 3. Steviol inhibits the proliferation of the human osteosarcoma U2OS cell line in a dose- and time-dependent manner. 4. Steviol can treat polycystic kidney disease, it slowed cyst growth, in part, by reducing AQP2 transcription, promoted proteasome, and lysosome-mediated AQP2 degradation.