2019年11月26日 · Timed degradation of the cyclin-dependent kinase inhibitor p27 Kip1 by the E3 ubiquitin ligase F-box protein SKP2 is critical for T-cell progression into cell cycle, coordinating proliferation...

These observations highlight the unexpected anti-neoplasm function of Troglitazone through targeting Skp2. Of note, using a high throughput platform, a total of 7368 chemical compounds are screened to identify novel Skp2 inhibitors by monitoring p27 level.

Taken together, inhibition of Skp2 functions (either proteolytic function or non-proteolytic function) is emerging as a promising and novel anti-cancer strategy. In the present review, we highlight the development of Skp2 inhibitors with different mechanisms of action.

To that end, the oncogenic properties of Skp2 are demonstrated by various genetic mouse models, highlighting the potential of Skp2 as a target for tackling cancer. In this article, we will describe the downstream substrates of Skp2 as well as upstream regulators for Skp2-SCF complex activity.

The current study identifies a specific Skp2 inhibitor compound #25 that phenocopies the effect of Skp2 deficiency to target tumorigenesis by upregulation of p27 tumor suppressor and inactivation of Akt oncoprotein.

Skp2 Inhibitor C1 (SKPin C1) is an S-phase kinase-related protein 2 (Skp2) inhibitor with an inhibitory effect on metastatic melanoma cells. Skp2 Inhibitor C1 slows the cell cycle, inhibits cell proliferation, and triggers apoptosis.

2024年2月14日 · The synergistic effect that we found when targeting Skp2 together with conventional chemotherapy indicate SKP2 inhibitors re-sensitize chemo-resistant tumors for cytotoxic killing.

In the current issue of EBioMedicine, Zhou et al. validated a new Skp2 inhibitor, dioscin, which is obtained from a natural steroid saponin, for potential use in colorectal cancer (CRC) treatment in the future .

2024年11月24日 · SKP2 inhibition significantly improved the antitumor efficacy of immune checkpoint blockade (ICB). Furthermore, SKP2 inhibition activated the cGAS/STING signal pathway and...

This Skp2 inhibitor restricts cancer stemness and potentiates sensitivity to chemotherapeutic agents in multiple animal tumor models. These findings identify a new novel small molecule that targets the Skp2 and reduces tumor growth by attenuating …

2019年4月25日 · A small molecule inhibitor of Skp2, named SKPin C1, was developed and confirmed to demonstrate an inhibitory effect on cell proliferation in human skin malignant melanoma cells. The present study tested the effect of SKPin C1 on normal B …

2020年6月1日 · Skp2 KO caused an increased accumulation of the Skp2-degradation target p27, a cyclin-dependent kinase inhibitor, which was confirmed as the mechanism of protection by using knock-in of a mutant p27 that was unable to bind to Skp2.

2024年2月1日 · Skp2 controls cancer cell growth and drug resistance by ubiquitinating modifications to a variety of proteins. This review emphasizes the multifaceted role of Skp2 in a wide range of cancers and the mechanisms involved, highlighting the potential of Skp2 as a therapeutic target in cancer.

A cell-permeable dimethylanilinomethylamine compound that inhibits SKP2-dependent cellular p27 Kip1 ubiquitination activity (10 to 30 µM; 16 h; in MM1.S myeloma and HeLa cultures) by preventing the incorporation of SKP2 into the Skp1-cullin1-F-box/SCF complex. Selectively induces the accumulation of known SCF SKP2 substrates (p21 Cip1, p27 Kip1, and p57 Kip2) …

2020年1月2日 · In the current issue of EBioMedicine, Zhou et al. validated a new Skp2 inhibitor, dioscin, which is obtained from a natural steroid saponin, for potential use in colorectal cancer (CRC) treatment in the future .

2024年9月1日 · The cell-cycle inhibitor p27, which is a SKP2 substrate, is targeted by SCF SKP2 for ubiquitination and degradation [13, 14]. The binding and recognition of p27 as a substrate requires CKS1B, which is an essential accessory protein for SCF SKP2 [ 15 ].

2013年8月1日 · In our study, we found that compound #25 is a specific Skp2 inhibitor by directly binding to the F box motif of Skp2, thus preventing Skp2-Skp1 interactions and subsequently abrogating Skp2 E3 ligase activity toward ubiquitination of p27 and Akt in vivo.

We propose that the primary mechanism of Skp2 inhibitor #25 on Skp2 E3 ligase activity is to prevent the assembly of newly synthesized Skp2-Skp1 complex by binding to Skp2. Another mode of #25 action against Skp2 activity is through its binding to preformed Skp1–Skp2 complex.

2025年2月28日 · Finally, we also demonstrated that SKP2 inhibitor treatment can significantly inhibit the growth of androgen-independent cell lines and enhance the efficacy of ADT. Our work reveals a novel role of ARv7 in regulating AIS and suggests that targeting the ARv7/SKP2/p27 axis could be a potential strategy to delay disease progression to the CRPC ...

2012年12月12日 · We identified small molecule inhibitors specific to SCF-Skp2 activity using in silico screens targeted to the binding interface for p27. These compounds selectively inhibited Skp2-mediated p27 degradation by reducing p27 binding through key …

「Skp2 Inhibitor C1」。富士フイルム和光純薬株式会社は、試験研究用試薬・抗体の製造販売および各種受託サービスを行っています。先端技術の研究から、ライフサイエンス関連、有機合成用や環境測定用試薬まで、幅広い分野で多種多様なニーズに応えています。

2022年6月25日 · A primary target of Skp2 is the cyclin-dependent kinase inhibitor p27 (CDKN1b) that regulates the cell cycle at several points. The RB1 tumour suppressor gene regulates Skp2 activity by...

DT204 is an Skp2 inhibitor identified by virtual and computational screening against multiple myeloma RPMI8226 cells. DT204 prevents Skp2 from incorporating into the SCF Skp2 complex by reducing Skp2 binding to Cullin-1, and treatment with DT204 increases p27 protein levels.

2 天之前 · The data showed that TOMM20 knockdown or HSP inhibitors of HSP70 or HSP90 alone decreased the protein levels of PSA (Fig. 6B, C) and the mRNA levels of KLK3 gene, while the combination of TOMM20 ...