Discovery of a σ1 receptor antagonist by combination of unbiased cell painting and thermal proteome profiling

Natural Product Alantolactone Targeting AKR1C1 Suppresses Cell Proliferation and Metastasis in Non-Small-Cell Lung Cancer

“…Although there are various methods that are available for target identification, PISA derived from TPP is the most suitable approach for natural products as it does not require any chemical modification to design a probe ( Gaetani et al, 2019 ). Through monitoring of changes in protein thermal stability across the whole proteome using multiplexed quantitative mass spectrometry, the target engagement of drugs in living cells would be identified in an unbiased manner ( Peuget et al, 2020 ; Corrales et al, 2021 ; Wilke et al, 2021 ). Notably, PISA employs the integral of the area under its melting curve instead of the determination of melting temperature by plotting the melting curve, which could significantly improve the low-throughput drawback of melting curve fitting in TPP ( Li et al, 2020 ).…”

Tandem mass tag-based thermal proteome profiling for the discovery of drug-protein interactions in cancer cells

“…There are very few published examples of TPP being used to identify primary effector targets. 1 , 18 , 19 , 20 , 21 A recently published review comprehensively describes recent developments in TPP applications and details all protein targets, including off-targets, that have been identified by TPP to-date. 22 …”

Dual Sigma-1 receptor antagonists and hydrogen sulfide-releasing compounds for pain treatment: Design, synthesis, and pharmacological evaluation

“…In addition, changes in capsaicin-induced mechanical hypersensitivity have been used to study the behavioral consequences of drug treatment in central sensitization in both humans and rodents [24,34,35]. Importantly, capsaicin-induced mechanical hypersensitivity has been used repeatedly to determine the σ1 agonistic/antagonistic properties of new compounds (including clinical candidates) [36][37][38], as σ1 antagonists are able to decrease sensory hypersensitivity while σ1 agonists reverse the effects of the former [35].…”