SRC-3 Regulation of regulatory T cell (Treg) function

Describes a model for SRC-3 as a coactivator that actively participates in protection from autoimmunity and may support immune evasion of cancers by contributing to the biology of Tregs.

Scientific Reports, 2021

Nikolai BC, Jain P, Cardenas DL, York B, Feng Q, McKenna NJ, Dasgupta S, Lonard DM, O’Malley BW. Steroid receptor coactivator 3 (SRC-3/AIB1) is enriched and functional in mouse and human Tregs. Sci Rep. 2021;11(1):3441. doi: 10.1038/s41598-021-82945-3. PMID: 33564037; PMCID: PMC7873281.

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Finds that steroid receptor coactivator stimulation with MCB-10-1 is a potential therapeutic strategy for reducing inflammation and oxidative damage that cause neurologic impairment following an acute ischemic stroke.

Front Mol Neurosci, 2022

McClendon LK, Garcia RL, Lazaro T, Robledo A, Vasandani V, Luna ZAE, Rao AS, Srivatsan A, Lonard DM, Dacso CC, Kan P, O’Malley BW. A steroid receptor coactivator small molecule “stimulator” attenuates post-stroke ischemic brain injury. Front Mol Neurosci. 2022 Dec 1;15:1055295. doi:10.3389/fnmol.2022.1055295. PMID: 36533127; PMCID: PMC9751323.

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SRC-3 small molecule stimulators

Steroid receptor coactivator stimulation with MCB-10-1 is a potential therapeutic strategy for reducing inflammation and oxidative damage that cause neurologic impairment following an acute ischemic stroke.

Front Mol Neurosci, 2022
Han SJ, Sung N, Wang J, O’Malley BW, Lonard DM. Steroid receptor coactivator-3 inhibition generates breast cancer antitumor immune microenvironment. Breast Cancer Res. 2022;24:73. doi: 10.1186/s13058-022-01568-2. PMID: 36316775; PMCID: PMC9620627.

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In this paper, we show that MCB-613, a potent small molecule stimulator of steroid receptor coactivators (SRCs) attenuates pathological remodeling post-MI. MCB-613 decreases infarct size, apoptosis, hypertrophy, and fibrosis while maintaining significant cardiac function.

Proc Natl Acad Sci, 2020
Mullany LK, Rohira AD, Leach JP, Kim JH, Monroe TO, Ortiz AR, Stork B, Gaber MW, Sarkar P, Sikora AG, Rosengart TK, York B, Song Y, Dacso CC, Lonard DM, Martin JF, O’Malley BW. A steroid receptor coactivator stimulator (MCB-613) attenuates adverse remodeling after myocardial infarction. Proc Natl Acad Sci USA. 2020;117(49):31353-31364. doi: 10.1073/pnas.2011614117. Epub 2020 Nov 23. PMID: 33229578; PMCID: PMC7733826.

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This paper demonstrates that inhibition of SRC-3 with a small molecule inhibitor can significantly inhibit pancreatic adenocarcinoma tumor growth in orthotopic pancreatic cancer mouse models. Combined with other data, this study establishes SRC-3 as a promising therapeutic target for pancreatic cancer treatment.

Cancer Lett. 2019
Xianzhou Song, Hui Chen, Chengwei Zhang, Yang Yu, Zhongyuan Chen, Han Liang, George Van Buren II, Amy L. McElhany, William E. Fisher, David M. Lonard, Bert W. O’Malley, and Jin Wang.

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