Small molecules targeting protein–protein interactions for cancer therapy

Wu, Dongbo; Yang, Li; Zheng, Lang; Xiao, Huan; Ouyang, Liang; Wang, Guan; Sun, Qiu

doi:10.1016/j.apsb.2023.05.035

Cited by 22 publications

(7 citation statements)

References 223 publications

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“…Moreover, several small-molecule Beclin-1 activators, such as AG-690/12088124 and piceatannol, were discovered as anti-cancer agents, which could encourage the discovery of Beclin-1-targeting small-molecule drugs. Furthermore, targeting Beclin-1 interactomes to alter their protein–protein interaction, such as Bcl-2 and ATG14L, provide more opportunities to regulate Beclin-1 functions for therapeutic purposes 304 , 305 , 306 . Meanwhile, biomedical engineering-based products, such as tumor acidity-responsive TpB protein and OVV-BECN1, also exhibited adequate tumor-suppressive activity, which may provide promising opportunities for developing Beclin-1-targeting approaches.…”

Section: Discussionmentioning

confidence: 99%

Targeting autophagy and beyond: Deconvoluting the complexity of Beclin-1 from biological function to cancer therapy

Ye,

Zhang,

Zhu

et al. 2023

Acta Pharmaceutica Sinica B

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Section: Discussionmentioning

confidence: 99%

Targeting autophagy and beyond: Deconvoluting the complexity of Beclin-1 from biological function to cancer therapy

Ye,

Zhang,

Zhu

et al. 2023

Acta Pharmaceutica Sinica B

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“…Advanced proteomics studies predicted 650,000 PPIs in the organism, much more than the number of proteins (20,000) 112 . Therefore, the discovery of PPI modulators attracting more and more attentions 113 , 114 . However, PPIs were regarded as “undruggable”, because protein–protein interfaces were much larger ( ca .…”

Section: Evolution-based Del Selection Strategiesmentioning

confidence: 99%

Evolution of chemistry and selection technology for DNA-encoded library

Ma,

Zhang,

Huang

et al. 2024

Acta Pharmaceutica Sinica B

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“…Computer learning and modeling changed the situation allowing one to discern binding ‘hot-spots’ on the shallow PPI interface and further allowing the determining parameters of structures of small molecules that disrupt the PPI. This approach has been used by the pharmaceutical industry to design new drugs 10 .…”

Section: Introductionmentioning

confidence: 99%

Pesticide chemical leads inhibiting protein-protein interactions

Ben Shushan,

Cohen,

Ben Naim

et al. 2024

Preprint

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Pesticides, especially herbicides, have revolutionized agriculture by providing energy-efficient solutions for pest control that replaces labor-intensive cultivation methods. However, the widespread evolution of pesticide resistance poses a significant challenge to current agriculture. Most pesticides function by binding to specific pockets on target enzymes, enabling a single mutation to confer resistance. An alternative approach is the disruption of protein-protein interactions (PPI), thus for resistance to occur, it requires complementary mutations on both interacting partners. Despite extensive efforts, no herbicides with new modes of action have been commercialized for decades. Thus, we focused on the discovery and design of small molecule inhibitors that target the interface of the PPI complex of O-acetylserine sulfhydrylase (OASS) and serine acetyltransferase (SAT), key plant enzymes involved in the biosynthesis of the essential amino acid cysteine. Using in silico filtering techniques on a virtual library of 30 million small molecules, we identified initial hits capable of binding OASS and interfering with its interaction with a peptide derived from SAT. Subsequently, we conducted chemical optimizations to evaluate biophysical enzyme disruption, followed by cellular and in-planta activity in plants. These new compounds described herein can serve as promising starting points for further optimization as herbicides acting on a new mode of action.

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Small molecules targeting protein–protein interactions for cancer therapy

Cited by 22 publications

References 223 publications

Targeting autophagy and beyond: Deconvoluting the complexity of Beclin-1 from biological function to cancer therapy

Targeting autophagy and beyond: Deconvoluting the complexity of Beclin-1 from biological function to cancer therapy

Evolution of chemistry and selection technology for DNA-encoded library

Pesticide chemical leads inhibiting protein-protein interactions

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