Skp2 Inhibitor

Skp2 inhibitor 3 is an orally active inhibitor of the Skp2-Cks1 complex, with an IC₅₀ of 4.86 μM. Skp2 inhibitor 3 reduces Skp2 protein expression while upregulating the expression of p21 and p27. Skp2 inhibitor 3 inhibits colony formation and migration of cancer cells, and induces cell cycle arrest at the S phase. Skp2 inhibitor 3 suppresses tumor growth in xenograft mice. Skp2 inhibitor 3 can be used in the research of gastric cancer and prostate cancer.

Skp2 inhibitor 2 is a Skp2-Cks1 protein-protein interaction inhibitor with a human IC₅₀ of 0.57 μM. Skp2 inhibitor 2 binds to Skp2 at the interaction interface to block Skp2-Cks1 complex formation. Skp2 inhibitor 2 can be used for the research of gastric cancer, non-small cell lung cancer, breast cancer, prostate cancer.

9-cis-UAB30 is a rexinoid agonist. 9-cis-UAB30 significantly decreases the proliferation, viability, and motility of both patient-derived xenografts (PDXs). 9-cis-UAB30 induced cell-cycle arrest as demonstrated by the significant increase in the percentage of cells in G1 and a decrease in the percentage of cells in S phase by downregulating SKP2 and/or 20S proteasome activity, which leads to increased p27kip1 protein stability. 9-cis-UAB30 downregulates the abundance of stem cell marker mRNAs (Oct4, Nanog, Sox2, nestin) and upregulates the abundance of differentiation marker mRNAs (β3-tubulin, NSE, HOXC9, GAP43). 9-cis-UAB30 has no adverse effects on the central nervous system and cardiovascular system at the tested dose. 9-cis-UAB30 can be used for the study of neuroblastoma, cutaneous T-cell lymphomas, and breast cancer.

p27 Analogue CP2 is a macrocyclic peptide inhibitor targeting the Cks1-Skp2-Skp1 complex (K_d = 32 nM). p27 Analogue CP2 blocks SCFSkp2/Cks1-mediated ubiquitylation and degradation of p27, restoring p27 levels and inhibiting cell proliferation. p27 Analogue CP2 is promising for research of cancers dependent on Skp2 overexpression such as breast cancer.