S6 Kinase

The 70 kDa ribosomal protein S6 kinase (p70 S6K) is a serine/threonine kinase. Two members of S6K family are named as S6K1 and S6K2, respectively. As the downstream target of PI3K/Akt/mTOR signaling pateway, S6K could be activated in response to many stimulus such as growth factors, cytokines and nutrients. [show the full text]

MAPK

PI3K mTOR GSK-3 DNA-PK ATM/ATR PDK BRAF AMPK screen library kit knockout PTEN MELK PI4K PIKfyve PP2A ETK/BMX Antioxidant ACSS2 SSTR ADC NUDIX PDPK1

Isoform-selective Products

p70 S6K p70 S6K1 RSK1 RSK2 RSK3 RSK4

All (19)
S6 Kinase Inhibitors (19)
New S6 Kinase Products

Cat.No.	Product Name	Information	Product Use Citations
S2843	BI-D1870	BI-D1870 is an ATP-competitive inhibitor of S6 ribosome for RSK1/2/3/4 with IC50 of 31 nM/24 nM/18 nM/15 nM in cell-free assays, respectively; 10- to 100-fold selectivity for RSK than MST2, GSK-3β, MARK3, CK1 and Aurora B. This compound exhibits anticancer attributes including the generation of reactive oxygen species (ROS) and increases in endoplasmic reticulum (ER) stress and autophagy.	J Biol Chem, 2025, 301(10):110643 Cells, 2024, 13(18)1546 Sci Rep, 2024, 14(1):9440
S2163	PF-4708671	PF-4708671 is a cell-permeable inhibitor of p70 ribosomal S6 kinase (S6K1 isoform) with K_i/IC50 of 20 nM/160 nM in cell-free assays, 400-fold greater selectivity for S6K1 than S6K2, and 4- and >20-fold selectivity for S6K1 than MSK1 and RSK1/2, respectively. This compound induces autophagy. It is the first S6K1-specific inhibitor to be reported.	Neoplasia, 2025, 66:101175 Mediators Inflamm, 2025, 2025:8108993 Nat Cell Biol, 2024, 10.1038/s41556-024-01473-0
S7698	LY2584702	LY2584702 is a selective, ATP-competitive p70S6K inhibitor with IC50 of 4 nM.	Life Sci Alliance, 2025, 8(11)e202503206 Sci Adv, 2025, 11(29):eadv1492 Mol Cell, 2024, S1097-2765(24)00832-3
S7704	LY2584702 Tosylate	LY2584702 Tosylate is a selective, ATP-competitive p70S6K inhibitor with IC50 of 4 nM. Phase 1.	Blood Adv, 2024, 8(15):3880-3892 Cell, 2023, 186(24):5328-5346.e26 Cell, 2023, 10.1016/j.cell.2023.09.027
S7871	LJI308	LJI308 is a potent, and pan-RSK (p90 ribosomal S6 kinase) inhibitor with IC50 of 6 nM, 4 nM, and 13 nM for RSK1, RSK2, and RSK3, respectively.	Nat Commun, 2024, 15(1):2089 J Exp Clin Cancer Res, 2022, 41-1:256 Cell Rep, 2022, 41(11):111827
S7870	LJH685	LJH685 is a potent pan-RSK inhibitor with IC50 of 6 nM, 5 nM and 4 nM for RSK1, RSK2, and RSK3, respectively.	Biol Pharm Bull, 2025, 48(2):172-176 Sci Adv, 2025, 11(36):eadw2568 Cell Rep, 2022, 38(11):110522
S3940	3'-Hydroxypterostilbene	3'-Hydroxypterostilbene (3'-HPT) is one of the active constituents of Sphaerophysa salsula and Pterocarpus marsupium which may be useful in treating different types of haematological malignancies. This compound, a natural pterostilbene analogue, effectively inhibits the growth of human colon cancer cells (IC50s of 9.0, 40.2, and 70.9 µM for COLO 205, HCT-116, and HT-29 cells, respectively) by inducing apoptosis and autophagy. It inhibits the PI3K/Akt/mTOR/p70S6K, and p38MAPK pathways and activates the ERK1/2, JNK1/2 MAPK pathways.	Int J Mol Sci, 2024, 25(18)9990
E1754	BRD7389	BRD7389 is an inhibitor of RSK family kinases with IC50 of 1.5 μM, 2.4 μM, and 1.2 μM for RSK1, RSK2, and RSK3, respectively. This compound also increases β-cell–specific gene expression in primary human islet cells.
S0385	S6K-18	S6K-18 is a highly selective inhibitor of ribosomal protein S6 kinase beta-1 (S6K1, p70S6K, p70-S6K).	Elife, 2024, 13RP92925 Item – Theses Canada, 2016,
E4345	L-Norvaline	L-Norvaline is a non-proteinogenic amino acid, an isomer of valine, and an inhibitor of arginase and p70 ribosomal S6 kinase 1 (p70S6K1) kinase. L-norvaline enhances NO production from activated macrophages.
E4690^New	Gingerenone A	Gingerenone A is a a polyphenol present in ginger, an inhibitor of p70 S6 (S6K1) and an activator of Nrf2-Gpx4 signaling pathway to alleviate ferroptosis in secondary liver injury in colitis. It exhibits anti-adipogenic, anti-lipogenic, anti-hyperglycemic, anti-obesity, and anti-inflammatory effects, and holds promise for research into anti-diabetic and anti-obesity drug development.
S1582	H-89 Dihydrochloride	H 89 2HCl is a potent PKA inhibitor with K_i of 48 nM in a cell-free assay, 10-fold selective for PKA than PKG,500-fold greater selectivity than PKC, MLCK, calmodulin kinase II and casein kinase I/II. H 89 2HCl induces autophagy.	Nat Commun, 2025, 16(1):7115 Cell Rep Med, 2025, 6(8):102254 Transl Neurodegener, 2025, 14(1):43
S1421	Staurosporine (STS)	Staurosporine (STS) is a potent PKC inhibitor for PKCα, PKCγ and PKCη with IC50 of 2 nM, 5 nM and 4 nM, less potent to PKCδ (20 nM), PKCε (73 nM) and little active to PKCζ (1086 nM) in cell-free assays. This compound also shows inhibitory activities on other kinases, such as PKA, PKG, S6K, CaMKII, etc. Phase 3.	Cell Metab, 2025, S1550-4131(25)00149-4 Mol Cell, 2025, 85(19):3711-3728.e11 EMBO J, 2025, 10.1038/s44318-025-00526-w
S1014	Bosutinib (SKI-606)	Bosutinib is a novel, dual Src/Abl inhibitor with IC50 of 1.2 nM and 1 nM in cell-free assays, respectively. Bosutinib also effectively decreases the activity of PI3K/AKT/mTOR, MAPK/ERK and JAK/STAT3 signaling pathways by blocking the phosphorylation levels of p-ERK, p-S6, and p-STAT3. Bosutinib promotes autophagy.	J Exp Clin Cancer Res, 2025, 44(1):290 Blood Adv, 2025, bloodadvances.2024015364 Biochem Pharmacol, 2025, 242(Pt 4):117412
S1558	AT7867	AT7867 is a potent ATP-competitive inhibitor of Akt1/2/3 and p70S6K/PKA with IC50 of 32 nM/17 nM/47 nM and 85 nM/20 nM in cell-free assays, respectively; this compound shows little activity outside the AGC kinase family.	Exp Gerontol, 2023, 173:112091 Cancers (Basel), 2022, 14(21)5215 Oncoimmunology, 2021, 10(1):1943234
S7563	AT13148	AT13148 is an oral, ATP-competitive, multi-AGC kinase inhibitor with IC50 of 38 nM/402 nM/50 nM, 8 nM, 3 nM, and 6 nM/4 nM for Akt1/2/3, p70S6K, PKA, and ROCKI/II, respectively. Phase 1.	Neoplasia, 2023, 10.1016/j.neo.2023.100948 Cancers (Basel), 2022, 14(23)5943 Br J Cancer, 2021, 10.1038/s41416-021-01442-6
S6385	Prexasertib (LY2606368)	Prexasertib (LY2606368, ACR 368) is a selective ATP competitor inhibitor of Chk1 and Chk2 with IC50s of 1 nM and 8 nM in cell-free assays, respectively. It also inhibits RSK1 with an IC50 of 9 nM in cell-free assay.	Cell Rep Med, 2025, S2666-3791(25)00151-X Mol Oncol, 2025, 19(6):1633-1650 Biomol Ther (Seoul), 2025, 33(3):458-469
S8518	AD80	AD80, a multikinase inhibitor, shows strong activity against human RET (c-RET), BRAF, S6K, and SRC but was much less active than either AD57 or AD58 against mTOR. The IC50 value for RET is 4 nM.	Nat Commun, 2022, 13(1):2500 Mol Cancer Res, 2020, 18(8):1176-1188 Mol Cancer Res, 2020, 1176-1188
S7752	Pluripotin (SC1)	Pluripotin (SC1) is a dual inhibitor of extracellular signal-regulated kinase 1 (ERK1, MAPK3) and RasGAP that maintains embryonic stem cell (ESC) self-renewal. It also inhibits RSK1, RSK2, RSK3 and RSK4 with IC50 of 0.5 µM, 2.5 µM, 3.3 µM and 10.0 µM, respectively.	J Clin Biochem Nutr, 2024, 74(2):97-107 Antiviral Res, 2018, 157:57-67 Reprod Domest Anim, 2018, 53(5):1052-1059
S2843	BI-D1870	BI-D1870 is an ATP-competitive inhibitor of S6 ribosome for RSK1/2/3/4 with IC50 of 31 nM/24 nM/18 nM/15 nM in cell-free assays, respectively; 10- to 100-fold selectivity for RSK than MST2, GSK-3β, MARK3, CK1 and Aurora B. This compound exhibits anticancer attributes including the generation of reactive oxygen species (ROS) and increases in endoplasmic reticulum (ER) stress and autophagy.	J Biol Chem, 2025, 301(10):110643 Cells, 2024, 13(18)1546 Sci Rep, 2024, 14(1):9440
S2163	PF-4708671	PF-4708671 is a cell-permeable inhibitor of p70 ribosomal S6 kinase (S6K1 isoform) with K_i/IC50 of 20 nM/160 nM in cell-free assays, 400-fold greater selectivity for S6K1 than S6K2, and 4- and >20-fold selectivity for S6K1 than MSK1 and RSK1/2, respectively. This compound induces autophagy. It is the first S6K1-specific inhibitor to be reported.	Neoplasia, 2025, 66:101175 Mediators Inflamm, 2025, 2025:8108993 Nat Cell Biol, 2024, 10.1038/s41556-024-01473-0
S7698	LY2584702	LY2584702 is a selective, ATP-competitive p70S6K inhibitor with IC50 of 4 nM.	Life Sci Alliance, 2025, 8(11)e202503206 Sci Adv, 2025, 11(29):eadv1492 Mol Cell, 2024, S1097-2765(24)00832-3
S7704	LY2584702 Tosylate	LY2584702 Tosylate is a selective, ATP-competitive p70S6K inhibitor with IC50 of 4 nM. Phase 1.	Blood Adv, 2024, 8(15):3880-3892 Cell, 2023, 186(24):5328-5346.e26 Cell, 2023, 10.1016/j.cell.2023.09.027
S7871	LJI308	LJI308 is a potent, and pan-RSK (p90 ribosomal S6 kinase) inhibitor with IC50 of 6 nM, 4 nM, and 13 nM for RSK1, RSK2, and RSK3, respectively.	Nat Commun, 2024, 15(1):2089 J Exp Clin Cancer Res, 2022, 41-1:256 Cell Rep, 2022, 41(11):111827
S7870	LJH685	LJH685 is a potent pan-RSK inhibitor with IC50 of 6 nM, 5 nM and 4 nM for RSK1, RSK2, and RSK3, respectively.	Biol Pharm Bull, 2025, 48(2):172-176 Sci Adv, 2025, 11(36):eadw2568 Cell Rep, 2022, 38(11):110522
S3940	3'-Hydroxypterostilbene	3'-Hydroxypterostilbene (3'-HPT) is one of the active constituents of Sphaerophysa salsula and Pterocarpus marsupium which may be useful in treating different types of haematological malignancies. This compound, a natural pterostilbene analogue, effectively inhibits the growth of human colon cancer cells (IC50s of 9.0, 40.2, and 70.9 µM for COLO 205, HCT-116, and HT-29 cells, respectively) by inducing apoptosis and autophagy. It inhibits the PI3K/Akt/mTOR/p70S6K, and p38MAPK pathways and activates the ERK1/2, JNK1/2 MAPK pathways.	Int J Mol Sci, 2024, 25(18)9990
E1754	BRD7389	BRD7389 is an inhibitor of RSK family kinases with IC50 of 1.5 μM, 2.4 μM, and 1.2 μM for RSK1, RSK2, and RSK3, respectively. This compound also increases β-cell–specific gene expression in primary human islet cells.
S0385	S6K-18	S6K-18 is a highly selective inhibitor of ribosomal protein S6 kinase beta-1 (S6K1, p70S6K, p70-S6K).	Elife, 2024, 13RP92925 Item – Theses Canada, 2016,
E4345	L-Norvaline	L-Norvaline is a non-proteinogenic amino acid, an isomer of valine, and an inhibitor of arginase and p70 ribosomal S6 kinase 1 (p70S6K1) kinase. L-norvaline enhances NO production from activated macrophages.
E4690^New	Gingerenone A	Gingerenone A is a a polyphenol present in ginger, an inhibitor of p70 S6 (S6K1) and an activator of Nrf2-Gpx4 signaling pathway to alleviate ferroptosis in secondary liver injury in colitis. It exhibits anti-adipogenic, anti-lipogenic, anti-hyperglycemic, anti-obesity, and anti-inflammatory effects, and holds promise for research into anti-diabetic and anti-obesity drug development.
S1582	H-89 Dihydrochloride	H 89 2HCl is a potent PKA inhibitor with K_i of 48 nM in a cell-free assay, 10-fold selective for PKA than PKG,500-fold greater selectivity than PKC, MLCK, calmodulin kinase II and casein kinase I/II. H 89 2HCl induces autophagy.	Nat Commun, 2025, 16(1):7115 Cell Rep Med, 2025, 6(8):102254 Transl Neurodegener, 2025, 14(1):43
S1421	Staurosporine (STS)	Staurosporine (STS) is a potent PKC inhibitor for PKCα, PKCγ and PKCη with IC50 of 2 nM, 5 nM and 4 nM, less potent to PKCδ (20 nM), PKCε (73 nM) and little active to PKCζ (1086 nM) in cell-free assays. This compound also shows inhibitory activities on other kinases, such as PKA, PKG, S6K, CaMKII, etc. Phase 3.	Cell Metab, 2025, S1550-4131(25)00149-4 Mol Cell, 2025, 85(19):3711-3728.e11 EMBO J, 2025, 10.1038/s44318-025-00526-w
S1014	Bosutinib (SKI-606)	Bosutinib is a novel, dual Src/Abl inhibitor with IC50 of 1.2 nM and 1 nM in cell-free assays, respectively. Bosutinib also effectively decreases the activity of PI3K/AKT/mTOR, MAPK/ERK and JAK/STAT3 signaling pathways by blocking the phosphorylation levels of p-ERK, p-S6, and p-STAT3. Bosutinib promotes autophagy.	J Exp Clin Cancer Res, 2025, 44(1):290 Blood Adv, 2025, bloodadvances.2024015364 Biochem Pharmacol, 2025, 242(Pt 4):117412
S1558	AT7867	AT7867 is a potent ATP-competitive inhibitor of Akt1/2/3 and p70S6K/PKA with IC50 of 32 nM/17 nM/47 nM and 85 nM/20 nM in cell-free assays, respectively; this compound shows little activity outside the AGC kinase family.	Exp Gerontol, 2023, 173:112091 Cancers (Basel), 2022, 14(21)5215 Oncoimmunology, 2021, 10(1):1943234
S7563	AT13148	AT13148 is an oral, ATP-competitive, multi-AGC kinase inhibitor with IC50 of 38 nM/402 nM/50 nM, 8 nM, 3 nM, and 6 nM/4 nM for Akt1/2/3, p70S6K, PKA, and ROCKI/II, respectively. Phase 1.	Neoplasia, 2023, 10.1016/j.neo.2023.100948 Cancers (Basel), 2022, 14(23)5943 Br J Cancer, 2021, 10.1038/s41416-021-01442-6
S6385	Prexasertib (LY2606368)	Prexasertib (LY2606368, ACR 368) is a selective ATP competitor inhibitor of Chk1 and Chk2 with IC50s of 1 nM and 8 nM in cell-free assays, respectively. It also inhibits RSK1 with an IC50 of 9 nM in cell-free assay.	Cell Rep Med, 2025, S2666-3791(25)00151-X Mol Oncol, 2025, 19(6):1633-1650 Biomol Ther (Seoul), 2025, 33(3):458-469
S8518	AD80	AD80, a multikinase inhibitor, shows strong activity against human RET (c-RET), BRAF, S6K, and SRC but was much less active than either AD57 or AD58 against mTOR. The IC50 value for RET is 4 nM.	Nat Commun, 2022, 13(1):2500 Mol Cancer Res, 2020, 18(8):1176-1188 Mol Cancer Res, 2020, 1176-1188
S7752	Pluripotin (SC1)	Pluripotin (SC1) is a dual inhibitor of extracellular signal-regulated kinase 1 (ERK1, MAPK3) and RasGAP that maintains embryonic stem cell (ESC) self-renewal. It also inhibits RSK1, RSK2, RSK3 and RSK4 with IC50 of 0.5 µM, 2.5 µM, 3.3 µM and 10.0 µM, respectively.	J Clin Biochem Nutr, 2024, 74(2):97-107 Antiviral Res, 2018, 157:57-67 Reprod Domest Anim, 2018, 53(5):1052-1059
E4690^New	Gingerenone A	Gingerenone A is a a polyphenol present in ginger, an inhibitor of p70 S6 (S6K1) and an activator of Nrf2-Gpx4 signaling pathway to alleviate ferroptosis in secondary liver injury in colitis. It exhibits anti-adipogenic, anti-lipogenic, anti-hyperglycemic, anti-obesity, and anti-inflammatory effects, and holds promise for research into anti-diabetic and anti-obesity drug development.

Signaling Pathway Map

The 70 kDa ribosomal protein S6 kinase (p70 S6K) is a serine/threonine kinase. There are two highly homologous members in S6K family, which are named as S6K1 and S6K2, respectively. Both S6Ks belong to the AGC family of serine/threonine kinases and they could be activated in response to many stimulus, like growth factors, insulin and cytokines. In turn, S6Ks phosphorylate its substrates including the ribosomal protein S6, elF4B, and SKAR. It was found that the activity of S6Ks could be controlled by mammalian target of rapamycin (mTOR) ^[2]. And then, direct phosphorylation of S6K1 by mTOR was confirmed ^{[3; 4]}. Therefore, the activity of S6K presented sensitive to rapamycin ^[8]. However, the sensitivity of S6Ks to rapamycin was found always changing. S6Ks became insensitive to rapamycin when the site T412 was phosphorylated ^[9]. Until recently, raptor has been proved to be responsible for T412 phosphorylation ^[6]. Besides, S6K−/− animals showed short-lived and were much smaller than wild type animals. A study suggested that this phenomenon was due to the control of S6K on cell growth rather than proliferation ^[5]. To date, S6Ks are also related to many serious diseases. For example, S6K1 showed overexpression in breast cancer patients ^[1]. With the understanding of the importance of S6K in human diseases, the demand for S6K-specific inhibitors increased rapidly. Fortunately, a novel inhibitor specific for S6K1, PF-4708671, was developed to facilitate the study of the functions of S6K1, at the same time, and S6K2 ^[7].