Cited by 211Prostate Cancer Treatment and ResearchEstrogen and related hormone effectsUrinary Bladder and Prostate Research

The DOI matches its Crossref record; 39 of the 41 references it cites were found in a registry or an index.

Development of a Small-Molecule Serum- and Glucocorticoid-Regulated Kinase-1 Antagonist and Its Evaluation as a Prostate Cancer Therapeutic

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Sherk, Andrea B., Frigo, Daniel E., Schnackenberg, Christine G., Bray, Jeffrey D., Laping, Nicholas J., Trizna, Walter, Hammond, Marlys, Patterson, Jaclyn R., Thompson, Scott K., Kazmin, Dmitri, Norris, John D., McDonnell, Donald P.·2008·Cancer Research

DOI 10.1158/0008-5472.can-08-1047PMC PMC2562281

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Abstract

Androgens, through their actions on the androgen receptor (AR), are required for the development of the prostate and contribute to the pathologic growth dysregulation observed in prostate cancers. Consequently, androgen ablation has become an essential component of the pharmacotherapy of prostate cancer. In this study, we explored the utility of targeting processes downstream of AR as an alternate approach for therapy. Specifically, we show that the serum and glucocorticoid-regulated kinase 1 (SGK1) gene is an androgen-regulated target gene in cellular models of prostate cancer. Furthermore, functional serum- and glucocorticoid-regulated kinase 1 (SGK1) protein, as determined by the phosphorylation of its target Nedd4-2, was also increased with androgen treatment. Importantly, we determined that RNA interference–mediated knockdown of SGK1 expression attenuates the androgen-mediated growth of the prostate cancer cell line LNCaP. Given these findings, we explored the utility of SGK1 as a therapeutic target in prostate cancer by developing and evaluating a small-molecule inhibitor of this enzyme. From these studies emerged GSK650394, a competitive inhibitor that quantitatively blocks the effect of androgens on LNCaP cell growth. Thus, in addition to androgen ablation, inhibition of pathways downstream of AR is likely to have therapeutic utility in prostate cancer. [Cancer Res 2008;68(18):7475–83]

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Activation of Phosphatidylinositol 3-Kinase/Akt Pathway by Androgen through Interaction of p85α, Androgen Receptor, and Src
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Retracted
PTEN , a Putative Protein Tyrosine Phosphatase Gene Mutated in Human Brain, Breast, and Prostate Cancer
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“Specifically, upon PI3K activation, SGK1 is phosphorylated at Ser 422 by an as yet unidentified kinase, referred to as the phosphoinositide-dependent protein kinase (PDK)-2, followed by the phosphorylation of Thr 256 within the activation loop of the SGK1 catalytic domain by PDK1 to become fully activated (19).”
Influential
Long-term results with immediate androgen suppression and external irradiation in patients with locally advanced prostate cancer (an EORTC study): a phase III randomised trial
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“Although 80% of patients with local or metastatic prostate cancer initially respond favorably to androgen ablation therapy, most patients eventually experience a relapse of the disease, which is then considered to be hormone refractory (2, 3).”
Molecular Mechanisms of Human Hypertension
Lifton, R. P., Gharavi, A. G., & Geller, D. S. (2001) · Cell · doi:10.1016/s0092-8674(01)00241-0 · Cited by 1,686 · cited 1×
“lacking the sgk1 gene have higher sodium excretion and lower blood pressure than wild-type mice when fed a low-sodium diet (33, 34).”
Activation of serum- and glucocorticoid-regulated protein kinase by agonists that activate phosphatidylinositide 3-kinase is mediated by 3-phosphoinositide-dependent protein kinase-1 (PDK1) and PDK2
Kobayashi, T., & Cohen, P. (1999) · Biochemical Journal · doi:10.1042/bj3390319 · Cited by 602 · cited 1×
“Specifically, upon PI3K activation, SGK1 is phosphorylated at Ser(422) by an as yet unidentified kinase, referred to as the phosphoinositide-dependent protein kinase (PDK)-2, followed by the phosphorylation of Thr(256) within the activation loop of the SGK1 catalytic domain by PDK1 to become fully activated (19).”
Serum and glucocorticoid‐inducible kinase (SGK) is a target of the PI 3‐kinase‐stimulated signaling pathway
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Characterization of sgk, a Novel Member of the Serine/Threonine Protein Kinase Gene Family Which Is Transcriptionally Induced by Glucocorticoids and Serum
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Gene Expression Analysis of Human Prostate Carcinoma during Hormonal Therapy Identifies Androgen-Responsive Genes and Mechanisms of Therapy Resistance
Holzbeierlein, J., Lal, P., LaTulippe, E., Smith, A., Satagopan, J., Zhang, L., Ryan, C., Smith, S., Scher, H., Scardino, P., et al. (2004) · The American Journal of Pathology · doi:10.1016/s0002-9440(10)63112-4 · Cited by 577 · cited 1×
“Although hormone-refractory disease is no longer responsive to androgen deprivation therapy, AR signaling pathways remain active and necessary for cancer progression (4).”
Characterization of the structure and regulation of two novel isoforms of serum- and glucocorticoid-induced protein kinase
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“Whereas SGK1 and SGK3 have been shown to phosphorylate many of the same target proteins in vitro , differences in subcellular localization suggest that these proteins regulate distinct signaling pathways (36).”
Updated results of the phase III Radiation Therapy Oncology Group (RTOG) trial 85-31 evaluating the potential benefit of androgen suppression following standard radiation therapy for unfavorable prognosis carcinoma of the prostate.
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“Although 80% of patients with local or metastatic prostate cancer initially respond favorably to androgen ablation therapy, most patients eventually experience a relapse of the disease, which is then considered to be hormone refractory (2, 3).”

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Development of a new analog of SGK1 inhibitor and its evaluation as a therapeutic molecule of colorectal cancer
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“GSK650394, a commercial inhibitor of SGK1, has previously been shown to antagonize SGK1 activity and inhibit prostate cancer cell growth [16].”
Background
Small-molecule control of cytokine function: new opportunities for treating immune disorders
Sundberg, T. B., Xavier, R. J., Schreiber, S. L., & Shamji, A. F. (2014) · Current Opinion in Chemical Biology · doi:10.1016/j.cbpa.2014.08.013 · Cited by 21
TGF 1 and SGK1-sensitive store-operated Ca2+ entry and Orai1 expression in endometrial Ishikawa cells
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“, 2011), it is not an innocent bystander but actively participates in tumor growth (Sherk et al., 2008; Nasir et al., 2009; Lang et al., 2010;Wang et al., 2010).”
Background
ENaC Modulators and Renal Disease
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“…changed by the development of a new generation of selective inhibitors of PI3K, such as PI103 (see Raynaud et al., 2007) and SGK1 (GSK659034; see Sherk et al., 2008) and by the identification of the target of rapamycin signalling complex 2 (TORC2) as the kinase respon- sible for the…”
Background
Heterocyclic indazole derivatives as SGK1 inhibitors, WO2008138448
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“Accordingly, the SGK1 inhibitor GSK650394 has been proposed for anticancer therapy [57].”
Background
Regulation of methylglyoxal-elicited leukocyte recruitment by endothelial SGK1/GSK3 signaling
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“Lastly, an antagonist of serum and glucocorticoid-regulated kinase 1 (SGK1), an androgen-regulated target gene, was found to block AR-mediated LNCaP cell growth [130], suggesting that the inhibition of GR-related pathways may have a therapeutic benefit in PCa [131,160].”
Background
SGK1, autophagy and cancer: an overview
Ghani, M. J. (2021) · Molecular Biology Reports · doi:10.1007/s11033-021-06836-6 · Cited by 22
“GSK650394 was the first reported inhibitor of SGK1 which is non-toxic and has anti-tumor effects with half-maximal inhibitory concentration (IC50) of 62 nM [53].”
Background
Serum- and glucocorticoid- inducible kinase 2, SGK2, is a novel autophagy regulator and modulates platinum drugs response in cancer cells
Ranzuglia, V., Lorenzon, I., Pellarin, I., Sonego, M., Dall’Acqua, A., D’Andrea, S., Lovisa, S., Segatto, I., Coan, M., Polesel, J., et al. (2020) · Oncogene · doi:10.1038/s41388-020-01433-6 · Cited by 21
“Accordingly, pretreatment of EOC cells for 24 h with increasing doses (from 35 to 65 μM) of the smallmolecule GSK650394, a specific SGK1/SGK2 inhibitor [37] significantly increased MDAH cells sensitivity to PT a”
Background
Two mechanisms involving the autophagic and proteasomal pathways process the metastasis suppressor protein, N-myc downstream regulated gene 1.
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The serum and glucocorticoid-regulated protein kinases (SGK) stimulate bovine herpesvirus 1 and herpes simplex virus 1 productive infection
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“We tested whether SGK1 function was necessary for the aldosterone effect observed in TRPM7-expressing HEK293 cells using 6 M GSK-650394, a compound that inhibits the enzymatic activity of SGK1 (52).”
Identification, structure modification, and characterization of potential small-molecule SGK3 inhibitors with novel scaffolds
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“It should be noted that, since SGKi also inhibits SGK2 [25], and as SGK1 primes NDRG1 for phosphorylation by glycogen synthase kinase-3 (GSK3; [2]), effects of this compound on the behaviour of NDRG1 may reflect interference with one or both of these inputs.”
Influential
Off-target pharmacological activity at various kinases: Potential functional and pathological side effects
Green, J. R., Mahalingaiah, P. K. S., Gopalakrishnan, S. M., Liguori, M. J., Mittelstadt, S. W., Blomme, E. A. G., & Vleet, T. R. V. (2023) · Journal of Pharmacological and Toxicological Methods · doi:10.1016/j.vascn.2023.107468 · Cited by 16
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“The specificity of GSK650394 for SGK1 over other related kinases is higher than 30-fold (22).”
Bioanalytical method validation, biopharmaceutical and pharmacokinetic evaluation of GSK-650394, a serum- and glucocorticoid-regulated kinase 1 inhibitor
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“We chose to use GSK650394 as an SGK1 inhibitor (25) as it was reported in some studies to stimulate the cells and successfully found that it is possible to exert a dynamic fluctuation behavior of SGK1 protein expression similar to that of γ-ray irradiation.”
Method
Identification of a new structural family of SGK1 inhibitors as potential neuroprotective agents
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The novel YAP target gene, SGK1, upregulates TAZ activity by blocking GSK3β-mediated TAZ destabilization
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Cytoplasmic translocation of MTA1 coregulator promotes de-repression of SGK1 transcription in hypoxic cancer cells
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Diverse Effects of ANXA7 and p53 on LNCaP Prostate Cancer Cells Are Associated with Regulation of SGK1 Transcription and Phosphorylation of the SGK1 Target FOXO3A
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“The SGK1-antagonists that block androgen effects on LNCaP growth are considered prostate cancer therapeutics [17].”
Background
Drugs That Inhibit Signalling Pathways for Tumor Cell Growth and Proliferation
Avendaño, C., & Menéndez, J. (2008) · Elsevier eBooks · doi:10.1016/b978-0-444-52824-7.00009-3 · Cited by 11
Elevated SGK1 increases Tau phosphorylation and microtubule instability in Alzheimer’s patient-derived cortical neurons
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“SGK1 overexpression signi ﬁ cantly increased Tau phosphorylation on S202/T205 (AT8 sites) and S214 in control neurons, but not beyond the already high levels in AD neurons (Fig.”
Computational insights into the active structure of SGK1 and its implication for ligand design
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SGK1 in Schwann cells is a potential molecular switch involved in axonal and glial regeneration during peripheral nerve injury
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Sulfasalazine alleviates neuropathic pain hypersensitivity in mice through inhibition of SGK-1 in the spinal cord
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AR-dependent phosphorylation and phospho-proteome targets in prostate cancer
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SGK1: master and commander of the fate of helper T cells
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Serum- and glucocorticoid-inducible kinase 1 activity in ventral tegmental area dopamine neurons regulates cocaine conditioned place preference but not cocaine self-administration
Doyle, M. A., Bali, V., Eagle, A. L., Stark, A. R., Fallon, B., Neve, R. L., Robison, A. J., & Mazei-Robison, M. S. (2021) · Neuropsychopharmacology · doi:10.1038/s41386-021-01032-3 · Cited by 9
“Particularly for commercially available GSK650394, the most widely used compound, these issues include specificity for SGK1 over other SGK isoforms and poor membrane permeability [45, 49].”
Background
Modulation of microglial activity by salt load and SGK1
Inoue, K., Morimoto, H., & Ueki, T. (2020) · NeuroReport · doi:10.1097/wnr.0000000000001449 · Cited by 8
Hit to lead optimization of the 4-trifluoromethylquinoline derivatives as novel SGK1 inhibitors with potent anti-prostate cancer activity
Li, C., Cheng, S., Yu, J. H., Zheng, Q., Yu, G., Mei, X., Zeng, X., Zeng, X., Liu, K., Xu, B., et al. (2025) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2025.117336 · Cited by 9
Induction of SGK1 via glucocorticoid-influenced clinical outcome of triple-negative breast cancer patients
Zhang, J., Miki, Y., Iwabuchi, E., Xu, J., Kanai, A., Sagara, Y., Ohi, Y., Rai, Y., Yamaguchi, R., Tanaka, M., et al. (2023) · Breast Cancer Research and Treatment · doi:10.1007/s10549-023-06990-4 · Cited by 13
“GSK650394 was the first SGK1 inhibitor reported to be non-toxic and anti-tumorigenic with an IC50 of 62 nM [36].”
Background
Small molecule H89 renders the phosphorylation of S6K1 and AKT resistant to mTOR inhibitors
Melick, C. H., & Jewell, J. L. (2020) · Biochemical Journal · doi:10.1042/bcj20190958 · Cited by 13
Drugs That Inhibit Signaling Pathways for Tumor Cell Growth and Proliferation
Avendaño, C., & Menéndez, J. C. (2015) · Elsevier eBooks · doi:10.1016/b978-0-444-62649-3.00010-7 · Cited by 14
Substrate recognition by Arg/Pro‐rich insert domain in calcium/calmodulin‐dependent protein kinase kinase for target protein kinases
Kaneshige, R., Ohtsuka, S., Harada, Y., Kawamata, I., Magari, M., Kanayama, N., Hatano, N., Sakagami, H., & Tokumitsu, H. (2022) · The FEBS Journal · doi:10.1111/febs.16467 · Cited by 7
SGK1 is essential for meiotic resumption in mammalian oocytes
del Llano, E., Iyyappan, R., Aleshkina, D., Mašek, T., Dvoran, M., Jiang, Z., Pospíšek, M., Kubelka, M., & Šušor, A. (2022) · European Journal of Cell Biology · doi:10.1016/j.ejcb.2022.151210 · Cited by 7
“To unveil this role, we treated GV oocytes with a specific SGK1 inhibitor (GSK-650394, Merck, Darmstadt, Germany; Sherk et al., 2008) which restricts SGK1 activity (and SGK2 with less affinity) and has been already used in several fields of research (Berdel et al., 2014; Bomberger et al., 2014;…”
Method
Identification and Kinetic Characterization of Serum- and Glucocorticoid-Regulated Kinase Inhibitors Using a Fluorescence Polarization–Based Assay
Kim, J., Kim, D., Jung, H., Lee, J.-H., & Hong, V. (2021) · SLAS discovery : advancing life sciences R & D · doi:10.1177/24725552211002465 · Cited by 7
The protective effects of gallic acid and SGK1 inhibitor on cardiac damage and genes involved in Ca2+ homeostasis in an isolated heart model of ischemia/reperfusion injury in rat
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“GSK650394 [GSK (a novel SGK inhibitor, relatively non-toxic with the formula C 25 H 22 N 2 O 2 (Sherk et al., 2008), CAS No.”
Identification of serum and glucocorticoid-regulated kinase 1 as a regulator of signal transducer and activator of transcription 3 signaling
Araki, T., Watanabe, Y., Okada, Y., Murakami, H., Ogo, N., & Asai, A. (2022) · Experimental Cell Research · doi:10.1016/j.yexcr.2022.113079 · Cited by 6
Global analysis of gene expression mediated by OX1 orexin receptor signaling in a hypothalamic cell line
Koesema, E., & Kodadek, T. J. (2017) · PLoS ONE · doi:10.1371/journal.pone.0188082 · Cited by 8
LRRC8A-containing anion channels promote glioblastoma proliferation via a WNK1/mTORC2-dependent mechanism
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Identification of Novel Inhibitors Targeting SGK1 via Ensemble-Based Virtual Screening Method, Biological Evaluation and Molecular Dynamics Simulation
Zhang, H., Shen, C., Zhang, H.-R., Qi, H.-Z., Hu, M., & Luo, Q.-Q. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23158635 · Cited by 6
Unlocking SGK1 inhibitor potential of bis-[1-N,7-N, pyrazolo tetraethoxyphthalimido{-4-(3,5-Dimethyl-4-(spiro-3-methylpyazolo)-1,7-dihydro-1H-dipyrazolo[3,4-b;4',3'-e]pyridin-8-yl)}]p-disubstituted phenyl compounds: a computational study
Verma, A. K., Ahmed, S. F., Hossain, M. S., Bhojiya, A. A., Upadhyay, S. K., Srivastava, A. K., Singh, N., Harina, H., Rahaman, M. M., & Bahadur, N. M. (2021) · Journal of Biomolecular Structure and Dynamics · doi:10.1080/07391102.2021.1988711 · Cited by 6
“Clinical studies are ongoing for the commercially available SGK1 inhibitors EMD638683 (Ackermann et al., 2011; Towhid et al., 2013) and GSK650394 (Sherk et al., 2008).”
BackgroundResultInfluential
SMURF and NEDD4: Sharp Shooters Monitor the Gate Keepers and Ion Traffic Controllers of Lead Astray Cell
Farooqi, A., Waseem, M. S., Riaz, A. M., & Bhatti, S. (2011) · Journal of Membrane Biology · doi:10.1007/s00232-011-9394-2 · Cited by 5
Inhibition of SGK1 potentiates the anticancer activity of PI3K inhibitor in NSCLC cells through modulation of mTORC1, p‑ERK and β‑catenin signaling
Kale, R. R., Samant, C., Bokare, A. M., Verma, M., Nandakumar, K., & Bhonde, M. (2023) · Biomedical Reports · doi:10.3892/br.2023.1676 · Cited by 4
“A selective and potent SGK1 inhibitor, GSK650394, with >30‑fold selectivity against AKT and other related kinases and >60‑fold selectivity for SGK1 over PDK1 was used (25).”
Method
Lipid droplets and autophagosomes together with chaperones fine‐tune expression of SGK1
Ghani, M. J., Gu, W., Chen, Z., & Canessa, C. M. (2022) · Journal of Cellular and Molecular Medicine · doi:10.1111/jcmm.17300 · Cited by 5
CRACking the Molecular Regulatory Mechanism of SOCE during Platelet Activation in Thrombo-Occlusive Diseases
Münzer, P., & Borst, O. (2022) · Cells · doi:10.3390/cells11040619 · Cited by 5
Inferring novel genes related to colorectal cancer via random walk with restart algorithm
Lu, S., Zhu, Z., & Lu, W. (2019) · Gene Therapy · doi:10.1038/s41434-019-0090-7 · Cited by 4
EAE-induced upregulation of mitochondrial MnSOD is associated with increases of mitochondrial SGK1 and Tom20 protein in the mouse kidney cortex
Hira, S., Packialakshmi, B., & Zhou, X. (2019) · The Journal of Physiological Sciences · doi:10.1007/s12576-019-00687-4 · Cited by 4
Cobalt-catalyzed C(sp3)–H/C(sp2)–H oxidative coupling between alkanes and benzamides
Li, S.-J., Wang, B., Dong, G., Li, C.-P., & Liu, H. (2018) · RSC Advances · doi:10.1039/c8ra01377b · Cited by 4
Advantages of PROTACs in achieving selective degradation of homologous protein families
Yang, L., Mao, X., Zhang, J., Shu, J., Huang, W., Dong, X., Chen, Y., & Wu, M. (2026) · Beilstein Journal of Organic Chemistry · doi:10.3762/bjoc.22.49 · Cited by 3
Discovery of a brain penetrant SGK1 inhibitor using a ligand- and structure-based virtual screening methodology
Madruga, E., Sanchez-Santos, C., Martı́nez, I., Ramírez, D., Gil, C., & Martı́nez, A. (2025) · Journal of Enzyme Inhibition and Medicinal Chemistry · doi:10.1080/14756366.2025.2546591 · Cited by 3
“…in its orientation. this was further supported by analysis of the dihedral angle formed between the phenyl and pyrrole rings (atoms 12, 14, 18, and 19), which showed significant variation within the 200–400 ns interval (Figure s1), coinciding with the conformational shift. according to these…”
A novel trifluoromethyl quinoline derivative targeting SGK1 inducing autophagy and apoptosis via regulating mTOR/FOXO3a pathway in glioblastoma
Xiong, Y.-F., Li, C., Yu, J., Chen, X.-Z., Cheng, S., Liu, X., Xu, B., Hu, X., Xu, G.-C., & Luo, H. (2024) · Arabian Journal of Chemistry · doi:10.1016/j.arabjc.2024.105909 · Cited by 3
GSK 650394 Inhibits Osteoclasts Differentiation and Prevents Bone Loss via Promoting the Activities of Antioxidant Enzymes In Vitro and In Vivo
Jin, L., Huo, S., Guo, C. Y., Liu, H.-Y., Xu, S., & Li, X. (2022) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2022/3458560 · Cited by 4
“GSK 650394 (GSK) was a highly selected inhibitor of SGK1 according to previous studies [26, 27], and the application of GSK could suppress the activation of osteoclast [25].”
Method
The Serum- and Glucocorticoid-Inducible Kinase 1 (SGK1) as a Novel Therapeutic Target in Mantle Cell Lymphoma
Li, J., Yu, H., Wang, X., Ye, Y., Fang, W., Ding, N., Mi, L., Ping, L., Wang, X., Song, Y., et al. (2022) · Cancer Control · doi:10.1177/10732748221143881 · Cited by 2
“SGK1, a serine/threonine protein kinase with 54% homology in its catalytic domain to AKT, has a critical role in several oncogenic signaling cascades involved in cell transformation, tumor progression and chemo/radioresistance.(18,27,35,36) SGK1 has been shown to be upregulated in several types of cancer, and is close…”
Background
Cross-regulation of notch/AKT and serum/glucocorticoid regulated kinase 1 (SGK1) in IL-4-stimulated human macrophages
Sangphech, N., & Palaga, T. (2021) · International Immunopharmacology · doi:10.1016/j.intimp.2021.108312 · Cited by 2
SGK1 (serum/glucocorticoid regulated kinase 1)
Menniti, M., Iuliano, R., D'Antona, L., Talarico, C., & Amato, R. (2017) · doi:10.4267/2042/62261 · Cited by 3
Do We Really Need New Trials on Fulvestrant in Prostate Cancer?
Féchon, A., & Droz, J. (2010) · Onkologie · doi:10.1159/000271605 · Cited by 3
Phosphorylation of UDP-glucose dehydrogenase increases glycosaminoglycan biosynthesis and promotes tumor cell motility, spheroid growth, and therapeutic resistance
Utz, A. R., Ma, L., Hilovsky, D., Zimmer, B. M., Allego, E., Fluharty, J., Narasimhan, P., Enders, J., Grady, G., Milici, M., et al. (2025) · Matrix Biology · doi:10.1016/j.matbio.2025.10.004 · Cited by 2
“Kinase inhibitor treatment concentrations were optimized based on published efficacy ranges [56–58] and the following were used for all assays: BIX02565 (20 μM), PF4708671 (20 μM), GSK650394 (40 μM).”
Unraveling the Potential of SGK1 in Osteoporosis: From Molecular Mechanisms to Therapeutic Targets
Yang, F., Chen, C., Chen, R., Yang, C., Liu, Z., Wen, L., Xiao, H., Geng, B., & Xia, Y. (2025) · Biomolecules · doi:10.3390/biom15050686 · Cited by 3
“The IC50 value of GSK650394 was determined to be 13 nM through the use of both the fluorescence polarization assay and the ATP mimetic assay [144].”
Bioinformatics Analysis of the Prognostic Significance of VPS16 in Hepatocellular Carcinoma and Its Role in Drug Screening
Gong, X.-M., Chen, T., Lin, C., Ping, H., Tong, X., Zhang, K., Chen, Z., Cai, C.-Y., Lu, Z., & Ke, H.-N. (2023) · BioMed Research International · doi:10.1155/2023/2501596 · Cited by 2
“GSK650394, a novel SGK inhibitor, inhibits insulin-induced phosphorylation of PKB-Ser473 at 3μM but has no effect on the phosphorylation of PRAS40-Ser246 in hormonedeprived cells or prevents insulin-induced phosphorylation of PKB-Ser473 phosphorylation [31, 32].”
Genetic silencing of AKT induces melanoma cell death
Parkman, G. L., Turapov, T., Kircher, D. A., Burnett, W. J., Stehn, C. M., O'Toole, K. T., Flaherty, R., Elmer, R. C., Culver, K. M., Foth, M., et al. (2022) · bioRxiv · doi:10.1101/2022.08.15.504039 · Cited by 2
“To that end, we employed GSK650394, a pharmacological inhibitor of SGK that selectively inhibits SGK1 and 2 but has very limited reported inhibitory effects on AKT (30).”
Method
Author's overview: identifying SARS-CoV-2 antiviral compounds
Diffley, J. F. X. (2021) · Biochemical Journal · doi:10.1042/bcj20210426 · Cited by 6
Design and screening of SGK1, Src dual inhibitors using pharmacophore models, molecular docking, and molecular dynamics simulation
Sun, C., Zhang, L., Gao, C., Zhang, H., Yu, R., & Kang, C. (2020) · New Journal of Chemistry · doi:10.1039/d0nj02249g · Cited by 4
Competitive and compensatory effects of androgen signaling and glucocorticoid signaling
Harada, N., Inui, H., & Yamaji, R. (2015) · Receptors & Clinical Investigation · doi:10.14800/rci.785 · Cited by 2
From virtual screening to reality: Identifying potent PI3Kγ inhibitors for inflammation treatment by harnessing machine learning and biological validation.
Jia, L., Cai, Y.-F., Chen, Y., Xu, L., Yu, L., Jin, J., & Zhu, J.-Y. (2026) · European journal of medicinal chemistry · doi:10.1016/j.ejmech.2026.119051 · Cited by 1
Inhibition of SGK1 Alleviates Apoptosis and Oxidative Stress in Dry Eye Disease by Activating FoxO3a-Mediated Autophagy
Tang, Y., Chen, Z., Jiang, J., Zhang, D., Chu, Y., Li, B., Zhang, Q. Y., & Hu, K. (2026) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.67.5.37 · Cited by 1
LRRC8A-containing anion channels promote glioblastoma proliferation via a WNK1/mTORC2-dependent mechanism
Fidaleo, A. M., Bach, M. D., Orbeta, S., Abdullaev, I., Martino, N., Adam, A. P., Boulos, M. A., Dulin, N., Paul, A. R., Kuo, Y.-H., et al. (2026) · Journal of Physiology · doi:10.1113/jp289036 · Cited by 1
“To explore the notion that changes in mTORC2 signalling are responsible for the impaired proliferation in LRRC8A knockdown cells, we first used a pharmacological approach to targeting the three canonical substrates of mTORC2 catalytic activity: AKT (MK-2206), SGK (GSK650394) (Sherk et al., 2008) and conventional PKC α…”
High-salt diet aggravates skin inflammation of psoriasis-like mouse model with CCL20‒CCR6 axis further activation
Hu, M., Cao, H., Zhang, L., Xia, Y., Zhang, J., Xue, F., Li, X., & Zheng, J. (2026) · JID Innovations · doi:10.1016/j.xjidi.2026.100451 · Cited by 1
Decoding the role of glucocorticoid-regulated kinase 1 in Alzheimer's disease: a promising path toward novel therapeutic strategies
Mittal, Y., Kumar, P., Joshi, K., & Aran, K. R. (2025) · Inflammopharmacology · doi:10.1007/s10787-025-01777-z · Cited by 1
Monocarboxylate transporter 4 promotes the migration of non‑cancerous L929 fibroblast cells by activating the IGF1/IGF1R/PIK3R3/SGK1 axis
Zhou, X., Wang, S., Li, Y., Zhao, H., Han, X., Yu, Y., Chen, Y., Yang, Y., Ma, X., Huo, H., et al. (2023) · Oncology Letters · doi:10.3892/ol.2023.14047 · Cited by 1
“HY‑15192; MedChemExpress), as an inhibitor of serum/glucocorticoid regulated kinase 1 (SGK1) activity (30,31).”
Background
KDM2B Silencing Elicits a Paracrine Mechanism Which Destabilizes SLUG, Promoting Differentiation of Basal-Like Breast Cancer Cells
Fraile, E. A., Chavdoula, E., Laliotis, G. I., Anastas, V., Serebrennikova, O., Paraskevopoulou, M., & Tsichlis, P. (2020) · bioRxiv · doi:10.1101/2020.05.21.109819 · Cited by 1
“…with AZD5363 (pan-Akt inhibitor) (Davies et al., 2012), R0-31-8220 (inhibitor of classical PKCs and PKCε) (McKenna and Hanson, 1993), GSK650394 (pan-SGK inhibitor) (Sherk et al., 2008), PF-4708671 (p70S6K inhibitor) (Pearce et al., 2010), or BI-D1870 (pp90RSK inhibitor) (Sapkota et al., 2007).”
Identification and characterization of human PEIG-1/GPRC5A as a 12-O-tetradecanoyl phorbol-13-acetate (TPA) and PKC-induced gene.
Mori, C., Valdivieso, Á. G., Clauzure, M., Massip-Copiz, M. M., Aguilar, M. Á., Cafferata, E., & Santa-Coloma, T. (2020) · Archives of Biochemistry and Biophysics · doi:10.1016/j.abb.2020.108375 · Cited by 1
Possible divergence of serum- and glucocorticoid-inducible kinase function in ischemic brain injury
Inoue, K. (2016) · Neural Regeneration Research · doi:10.4103/1673-5374.191202 · Cited by 1
“There are two commercially available SGK inhibitors, gsk650394 and EMD638683, which have been used for in vivo animal studies without any remarkable side effects (Sherk et al., 2008; Ackermann et al., 2011).”
Background
Small-molecule inhibitors of SGK1: Structural basis, structure-activity relationships, and therapeutic perspectives
Xie, J., Wu, W., Zhu, G., Xian, J., Ouyang, L., Zhang, Y., & Wang, Y. (2026) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2026.119253
Structure-optimized 4-trifluoromethylquinoline derivatives: Dual enhancement of SGK1 inhibition and anti-prostate cancer efficacy.
Zhou, Y.-F., Cheng, S., Li, C., Liu, X.-Y., Yu, J., Yu, G., Yi, P., Zeng, X.-P., Tu, W., Meng, X., et al. (2026) · Bioorganic chemistry (Print) · doi:10.1016/j.bioorg.2026.110032
Hyperosmolar stress induces monocyte chemoattractant protein 1 expression in retinal pigmented epithelial arising retinal pigmented epithelial 19 cells
Hamou, M. O., Masset, M., Weber, C., Scifo, L., Libert, S., Bryla, A., Grégoire, F., Delforge, V., Bolaky, N., Datlibagi, A., et al. (2025) · Molecular vision · doi:10.63500/mv_v31_380
Regulation of DVL2 ubiquitylation by USP9X biases participation in canonical or non-canonical WNT signalling
Nielsen, C. P., Jernigan, K. K., Diggins, N. L., Webb, D., & MacGurn, J. (2018) · bioRxiv · doi:10.1101/289595

Authors: Sherk, A. B., Frigo, D. E., Schnackenberg, C. G., Bray, J. D., Laping, N. J., Trizna, W., Hammond, M., Patterson, J. R., Thompson, S. K., Kazmin, D., Norris, J. D., & McDonnell, D. P.
Affiliations: Duke Medical Center (US)
Houston Methodist (US)
GlaxoSmithKline (United States) (US)
ORCID: Frigo, Daniel E.
Patterson, Jaclyn R.
Kazmin, Dmitri
Norris, John D.
McDonnell, Donald P.
Venue: Cancer Research
Publisher: American Association for Cancer Research (AACR)
Published: 2008-09-14
Volume: 68
Issue: 18
Pages: 7475-7483
ISSN: 0008-5472 (ISSN-L)
1538-7445
DOI: 10.1158/0008-5472.can-08-1047
PMC: PMC2562281
OpenAlex: W2127577957
Cited by: 211
References: 41
Citations by year: 2026: 11 · 2025: 9 · 2024: 7 · 2023: 12 · 2022: 19 · 2021: 20 · 2020: 17 · 2019: 10 · 2018: 12 · 2017: 12 · 2016: 13 · 2015: 12 · 2014: 14 · 2013: 8 · 2012: 9
FWCI: 8.26
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: Cancer Research (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
Funders: U.S. Department of Defense
GlaxoSmithKline
University of Dundee
National Institutes of Health
National Institute of Diabetes and Digestive and Kidney Diseases (F32DK072794, R01DK065251)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Prostate Cancer Treatment and Research
Life Sciences › Biochemistry, Genetics and Molecular Biology › Endocrinology › Estrogen and related hormone effects
Health Sciences › Medicine › Urology › Urinary Bladder and Prostate Research
Keywords: SGK1, prostate cancer, androgen receptor, androgen signaling, Nedd4-2, small-molecule kinase inhibitors, LNCaP cells, androgen deprivation therapy
MeSH terms: Serum-Glucocorticoid Regulated Kinases, Benzoates, HeLa Cells, Humans, Male, Prostatic Neoplasms, Receptors, Androgen, RNA, Messenger, Metribolone, Up-Regulation, Protein Serine-Threonine Kinases, Immediate-Early Proteins, Bridged Bicyclo Compounds, Heterocyclic, RNA, Small Interfering, Cell Line, Tumor, Protein Kinase Inhibitors, Cell Growth Processes

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Development of a Small-Molecule Serum- and Glucocorticoid-Regulated Kinase-1 Antagonist and Its Evaluation as a Prostate Cancer Therapeutic

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