# HTR2B antagonists sensitize uveal melanoma cells to Gαq inhibitor YM-254890 in cell lines

- Published: 2026-11-12 08:27 UTC
- Section: Life & Health › Medicine
- Tags: uveal melanoma, HTR2B antagonists, Gαq-Q209L, Gαq inhibitor YM-254890, G protein–coupled receptors, serotonin receptor 2B, intraocular malignancy, Gα11 mutations, Science Signaling
- URL: https://realtech.media/news/rt-51d976571d15548a7dc386e7_htr2b_antagonists_sensitize/

**In uveal melanoma cell lines, blocking the serotonin receptor HTR2B increased sensitivity to a Gαq inhibitor, although the antagonists alone had little to no inhibitory effect.**

![HTR2B antagonists sensitize uveal melanoma cells to Gαq inhibitor YM-254890 in cell lines](https://realtech.media/media/2026/11/26199c1f0f9f4e0d.jpg)
*Godart, Thomas, Wikimedia Commons, CC BY 4.0*

Jenna Aumiller and colleagues report in Science Signaling that Gq-coupled G protein–coupled receptors (GPCRs), including the serotonin receptor HTR2B, enhance oncogenic signaling of the mutant G protein subunit Gαq-Q209L in uveal melanoma cells [1]. Antagonists of HTR2B increased the sensitivity of these cells to the Gαq-specific inhibitor YM-254890 [1]. The experiments were performed on cultured cells, not in patients.

## Mutant Gαq and its receptors

Uveal melanoma (UM) is the most common intraocular malignancy in adults [1]. More than 90% of patients carry Q209L or Q209P mutations in the Gαq and Gα11 proteins [1]. Glutamine at position 209 of G protein α subunits is required to terminate signaling that GPCRs initiate through heterotrimeric G proteins [1].

Mutationally active Gα subunits have been thought to signal independently of GPCRs, although some may retain the ability to bind them [1]. The authors found that Gq-coupled GPCRs, including HTR2B, enhanced the oncogenic signaling of Gαq-QL [1]. According to the journal's summary of the work, stimulation of these receptors also promoted cell proliferation in a range of UM cell lines. The same summary notes that UM metastasizes in about 50% of patients and has no effective therapies.

## HTR2B antagonists and YM-254890

HTR2B antagonists alone had little to no inhibitory effect on the cells [1]. Combined with YM-254890, however, they increased the sensitivity of UM cells to the inhibitor, as measured by signaling, cell viability and proliferation assays [1].

In a further experiment, UM cells were treated with HTR2B antagonists and low concentrations of YM-254890. This shifted endogenous Gαq-QL/QP mutants into an inactive conformation to a greater extent than YM-254890 alone [1]. The authors conclude that Gq-coupled GPCRs enhance the oncogenicity of mutationally active Gαq proteins, and that antagonism of HTR2B promotes an inactive state of Gαq-QL/QP and increases sensitivity to a Gαq inhibitor [1].

The summary published with the study states that Gαq inhibitors of this type are currently too toxic for use in patients. The results come from cell-based assays and do not establish an effect in animals or humans.

## Sources

1. [Science Signaling](https://doi.org/10.1126/scisignal.aeg1191)
2. [news-medical.net](https://www.news-medical.net/news/20261111/Blocking-serotonin-receptors-makes-eye-cancer-cells-sensitive-to-drugs.aspx)

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Source: RealTech, realtech.media — https://realtech.media/news/rt-51d976571d15548a7dc386e7_htr2b_antagonists_sensitize/