4.6 Review

PROTACs for BRDs proteins in cancer therapy: a review

Related references

Note: Only part of the references are listed.
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Summary: This study designed and synthesized a specific and potent BRD4-PROTAC with excellent selective cytotoxicity, showing significant anticancer activity in prostate cancer cell lines, which could be a promising drug candidate for AR-positive prostate cancer.

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Summary: PROTACs are a novel drug discovery paradigm that utilizes the protein degradation pathway for target degradation, with VHL-based PROTACs emerging as a promising approach for treating diseases that are difficult to be dealt with by conventional methods. Advances in VHL-based PROTACs have been summarized in this review, highlighting the opportunities and challenges in this area.

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ATF2 inhibits ani-tumor effects of BET inhibitor in a negative feedback manner by attenuating ferroptosis

Lina Wang et al.

Summary: The study revealed that BET inhibitor may inhibit the growth of cancer cells such as breast cancer by activating ATF2, thereby reducing BETi-induced cell death. ATF2 increases NRF2 expression, inhibiting ferroptosis induced by BETi.

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Summary: Small molecule inhibitors play important roles in targeting proteins, but face challenges in drug selectivity and therapy resistance. PROTACs are a new class of molecules that can achieve complete target protein degradation in a catalytical fashion.

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Summary: PROTACs, a novel technology targeting protein degradation by utilizing ubiquitin E3 ligase, have shown promising potential especially in CRBN-based PROTACs like ARV-110 and ARV-471. Extensively explored worldwide, PROTACs have excelled in various diseases and are considered for therapeutic interventions.

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Summary: PROTACs are emerging as a promising therapeutic modality for degrading intracellular protein targets, but potential toxicity in normal cells limits their applications. By conjugating a folate group to a ligand of the VHL E3 ubiquitin ligase, a cancer cell selective delivery strategy for PROTACs was developed to achieve targeted degradation of proteins of interest in cancer cells. Folate-PROTACs provide a platform for selective degradation of proteins of interest in cancer cells.

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Shipeng He et al.

Summary: The aptamer-PROTAC conjugation strategy shows potential in improving the tumor-specific targeting ability and in vivo antitumor potency of conventional PROTACs, paving the way for the design of tumor-specific targeting PROTACs.

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