2-Bromohexadecanoic acid

2‑Bromohexadecanoic acid (CAS: 18263-25-7) is a widely used tool compound for inhibiting protein S‑palmitoylation. It can be converted intracellularly to 2‑bromopalmitoyl‑CoA and undergo covalent modification, thereby acting as a broad‑spectrum inhibitor of the DHHC (Asp‑His‑His‑Cys) family of palmitoyltransferases (PATs).

In addition to affecting membrane localization and signal transduction, 2‑BP can also inhibit pyroptosis mediated by the BAK/BAX‑caspase‑3‑GSDME pathway under specific conditions. Under chemotherapeutic conditions, palmitoylation of GSDME‑C promotes BAK/BAX‑caspase‑3‑GSDME‑dependent pyroptosis, whereas 2‑BP suppresses GSDME‑C palmitoylation and blocks pyroptosis.

In in vitro purified enzyme assays, the IC₅₀ of 2‑BP against human zDHHC20 is approximately 2.02 ± 0.29 µM (around 5.33 ± 0.77 µM by the acyl‑cLIP method). However, due to its wide range of targets and non‑selectivity, it is recommended to verify the mechanism in combination with genetic or orthogonal approaches.

References:

[1] Qiu T, Azizi SA, Brookes N, Lan T, Dickinson BC. A High-Throughput Fluorescent Turn-On Assay for Inhibitors of DHHC Family Proteins. ACS Chem Biol. 2022 Aug 19;17(8):2018-2023. doi: 10.1021/acschembio.2c00193. Epub 2022 Jul 11. PMID: 35816339; PMCID: PMC9391280.

[2]Davda D, El Azzouny MA, Tom CT, Hernandez JL, Majmudar JD, Kennedy RT, Martin BR. Profiling targets of the irreversible palmitoylation inhibitor 2-bromopalmitate. ACS Chem Biol. 2013 Sep 20;8(9):1912-7. doi: 10.1021/cb400380s. Epub 2013 Jul 25. PMID: 23844586; PMCID: PMC3892994.

[3] Hu L, Chen M, Chen X, Zhao C, Fang Z, Wang H, Dai H. Chemotherapy-induced pyroptosis is mediated by BAK/BAX-caspase-3-GSDME pathway and inhibited by 2-bromopalmitate. Cell Death Dis. 2020 Apr 24;11(4):281. doi: 10.1038/s41419-020-2476-2. Erratum in: Cell Death Dis. 2024 Sep 4;15(9):652. doi: 10.1038/s41419-024-07031-8. PMID: 32332857; PMCID: PMC7181755.