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Jianjun Cheng

6 papers in the library · 376 citations · publishing 2022-2026

Papers

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Targeting peripheral 5-HT2AR enhances antitumor immunity in colorectal cancer.

Cell August 1, 2026 Yating Wen, Lingjie Tang, Wenwen Duan et al.

Cancer remains a leading cause of morbidity and mortality worldwide. While classical psychedelics have been used clinically to treat cancer-associated psychiatric disorders, their impact on tumor progression is unclear. Here, we show that by targeting the serotonin receptor 5-HT2AR, lysergic acid diethylamide (LSD) enhances CD8+ T cell-mediated antitumor immunity and suppresses colorectal...

Structure-Guided Design of Novel 5-HT 2A Partial Agonists as Psychedelic Analogues with Antidepressant Effects

Journal of Medicinal Chemistry October 14, 2025 Rongyan Li, Hong Yan, Yujin Chen et al. 1 citation

Depression is primarily treated with selective serotonin reuptake inhibitors (SSRIs), which are limited by delayed onset of effects and low rates of remission. Recent studies showed that serotonergic psychedelics such as psilocybin can reduce depressive symptoms both rapidly and enduringly. Such effects have been associated with the activation of the serotonin 2A (5-HT2A) receptor in the...

Inhibition of SERT and NMDAR synergistically confers rapid antidepressant effects of ketamine

National Science Review September 5, 2025 Huoqing Luo, Ming Chen, Yingjie Ning et al. 1 citation

-methyl-d-aspartate receptor (NMDAR) blockade is crucial for the rapid antidepressant effects of ketamine, the involvement of other mechanisms remains contentious, particularly regarding the role of serotonin, a key neurotransmitter in the target of traditional antidepressants. Here, we demonstrate that ketamine elevates serotonin levels by inhibiting the serotonin transporter (SERT). A...

Structural basis of psychedelic LSD recognition at dopamine D1 receptor.

Neuron October 9, 2024 Luyu Fan, Youwen Zhuang, Hongyu Wu et al. 6 citations

Understanding the kinetics of LSD in receptors and subsequent induced signaling is crucial for comprehending both the psychoactive and therapeutic effects of LSD. Despite extensive research on LSD's interactions with serotonin 2A and 2B receptors, its behavior on other targets, including dopamine receptors, has remained elusive. Here, we present cryo-EM structures of LSD/PF6142-bound dopamine...

Serotonin 2A Receptor (5-HT2AR) Agonists: Psychedelics and Non-Hallucinogenic Analogues as Emerging Antidepressants

Chemical Reviews November 30, 2023 Wenwen Duan, Dongmei Cao, Sheng Wang et al. 62 citations

Psychedelics make up a group of psychoactive compounds that induce hallucinogenic effects by activating the serotonin 2A receptor (5-HT2AR). Clinical trials have demonstrated the traditional psychedelic substances like psilocybin as a class of rapid-acting and long-lasting antidepressants. However, there is a pressing need for rationally designed 5-HT2AR agonists that possess optimal...

Structure-based discovery of nonhallucinogenic psychedelic analogs

Science January 27, 2022 Dongmei Cao, Jing Yu, Huan Wang et al. 306 citations

Drugs that target the human serotonin 2A receptor (5-HT 2A R) are used to treat neuropsychiatric diseases; however, many have hallucinogenic effects, hampering their use. Here, we present structures of 5-HT 2A R complexed with the psychedelic drugs psilocin (the active metabolite of psilocybin) and d -lysergic acid diethylamide (LSD), as well as the endogenous neurotransmitter serotonin and the...