Table 2.
In vivo studies of the ubiquitin inhibitors supporting the suppression of tumors.
| S. No. | Drug | Cancer | Signaling Pathway | Animal Models | Reference |
|---|---|---|---|---|---|
| 1. | RNF152 | Colorectal cancer | It is inactivating mTORC1 to induce autophagy and apoptotic cell death. | Immunodeficient nude mice | [171] |
| 2. | RITA (2,5-bis[5-hydroxymethyl2-thienyl] furan, NSC 652287) | Renal carcinoma | Block TP53–mdm2 complex and reactivation of p53 and Induction of Tumor cell Apoptosis | Mouse xenograft model | [172] |
| 3. | RA-9 | Ovarian cancer | Apoptosis and proteotoxic stress | Mice xenograft model | [173] |
| 4. | WP1130 | T-cell acute lymphoblastic leukemia | Induces apoptosis by accelerating the collapse of mitochondrial transmembrane potential via USP24-Mcl-1 axis | Tumor xenografts in NOD-SCID mice | [174] |
| 5. | The bis-benzylidine piperidone RA190 | Hepatocellular carcinoma | Nuclear factor κB (NF-κB) signaling | Male nude mice CAnN.Cg-Foxn1nu/CrlNarl | [175] |
| 6. | O-phenanthroline (OPA) | Multiple myeloma | Caspase cascade and endoplasmic stress response signaling | Murine xenograft model of human MM | [176] |
| 7. | Nutlin-3a | Osteosarcoma | Competitively binds the mdm2-p53 interacting site, activates p53 pathway | Human xenograft OS animal model with SAOS-2, U2OS, MG63 cell lines in SCID mice | [177] |
| 8. | GDC-0152 | Glioblastomas | Antagonists of the inhibitor of IAPs Postponed tumor formation and slowed down tumor growth |
U87MG- iRFP cell grafted mice | [178] |
| 9. | SM-406/AT-406 | Human cancer cell (ovarian and breast cancer) | Antagonizes XIAP BIR3 induces rapid degradation of cellular cIAP1 protein | SCID mice bearing MDA-MB-231 xenograft tumors | [179] |
| 10. | Oridonin | Breast cancer | Tumor suppressive effect via inhibiting Notch receptors expression | Male BALB/C athymic nude mice | [180] |
| 11. | MLN4924 | Human urothelial cell carcinoma, cervical cancer, renal carcinoma, pharyngeal squamous carcinoma |
Inhibits cell viability and induced apoptosis in HUVECs (human umbilical vascular endothelial cells) | Xenograft SCID mice | [181] |
| 12. | P5091 | Colorectal cancer | Elevated mRNA level of IFN-γ and TNF-α | Female BALB/c mice (CT26 xenograft model) | [182] |
| 13. | bAP15 | Ovarian cancer | Regulating TGF-β signaling, dephosphorylating Smad2, inducing apoptosis | Mice xenograft models of SKOV3 | [183] |
| 14. | PR-619 | Bladder urothelial carcinoma (UC) | Suppression of the Bcl-2 level | Nude mice Xenograft Matrigel culture | [184] |
| 15. | CEP1612 [phthalimide-(CH2)8CH-(cyclopentyl) CO-Arg(NO2)-Leu-H] | Human lung adenocarcinoma | Accumulation of p21WAF1 and p27KIP1, inducing apoptosis | A-549 tumor-bearing nude mice | [185] |
| 16. | Curcumin | Human colon cancer | Inhibit the proteasome and induce apoptosis | HCT-116 tumor-bearing ICR SCID mice | [186] |
| 17. | P5091 | Multiple Myeloma Cells | Inhibited USP7 activity, decreased HDM2, and increased p21 levels, induces apoptosis | Human plasmacytoma xenograft and SCID-hu mouse models | [155] |
| 18. | ECRG4 | Esophageal cancer | Inhibits NF-κB expression and nuclear translocation, attenuates NF-κB target gene COX-2 expression | BALB/c nude mice | [187] |
| 19. | 8-(tosylamino) quinoline (8-TQ) | Human cancer cells | Inhibition of molecular signaling machineries composed of phosphoinositide 3-kinase (PI3K)/phosphoinositide-dependent kinase-1 (PDK1)/Akt and extracellular-signal-regulated kinase (ERK) | murine T-cell lymphoma RMA cells in mice | [188] |
| 20. | VLX1570 | Multiple myeloma | Decrease in ERK phosphorylation; USP14 inhibitor | Xenograft model in immunocompromised mice | [189] |
| 21. | b-AP15 | Large B cell lymphoma | Inhibits Wnt/β-catenin and TGFβ/Smad pathways; USP14 and UCHL5 deubiquitinases | Mouse xenograft models of SU-DHL-4 and SU-DHL-2 cells | [190] |