Mutations in the RAS genes have been recognized as major oncogenes with a high occurrence rate in human cancers. RAS proteins act as molecular switches that cycle between an active, GTP-bound state and an inactive, GDP-bound state. Activated by guanine nucleotide exchange factors (GEFs), RAS in its GTP bound state interacts with a number of effectors. The most-studied GEF for RAS is the protein Son of Sevenless (SOS) for which two human isoforms, SOS1 and SOS2, are known[1]. BAY-293, a valuable chemical probe, blocks RAS activation via disruption of the KRAS-SOS1 interaction with an IC50 of 21 nM. BAY-293 is a potent inhibitor of SOS1[1]. BAY-293 (595 nM-3580 nM; 72h) shows efficient antiproliferative activity against wild-type KRAS cell lines (K-562, MOLM-13) and cell lines with KRASG12C mutation (NCI-H358, Calu-1). BAY-293 efficiently inhibited pERK (extracellular signal-regulated kinase) levels in K-562 cells after incubation for 60 min without affecting total protein levels of ERK[1].
作用机制
The side-chain amino group of BAY-293 forms two new hydrogen bonds, to Asp887 and Tyr884, and is in a favorable position for a cation–π interaction with the side chain of Tyr884.
BAY-293 细胞实验
Cell Line
Concentration
Treated Time
Description
References
RD cells
0.2 µM
BAY-293 significantly reduced MYC expression in RD cells.
Sci Rep. 2025 Jan 23;15(1):2893.
BH837
3.7 µM
4 days
Test the cytotoxicity of BAY-293 against NSCLC and PDAC cell lines
Transl Oncol. 2021 Dec;14(12):101230.
BH828
1.7 µM
4 days
Test the cytotoxicity of BAY-293 against NSCLC and PDAC cell lines
Transl Oncol. 2021 Dec;14(12):101230.
BxPC3
5 µM
4 days
Test the synergy of BAY-293 with 2-DG, showing synergistic effects.
Discov Oncol. 2022 Sep 1;13(1):84.
AsPC1
5 µM
4 days
Test the synergy of BAY-293 with 2-DG, showing synergistic effects.
Discov Oncol. 2022 Sep 1;13(1):84.
TE671 cells
0.2 µM
BAY-293 significantly reduced MYC expression in TE671 cells.
Sci Rep. 2025 Jan 23;15(1):2893.
KCL-22-IMR cells
1.932 μM (alone), 1.732 μM (combined with imatinib)
BAY-293 alone or in combination with imatinib showed similar inhibitory effects on the proliferation of KCL-22-IMR cells.
Mol Ther Oncolytics. 2021 Nov 20;23:560-570.
KCL-22 cells
0.4, 0.8, 1.2, 1.6, 2.0 μM
48 hours
BAY-293 inhibited the proliferation of KCL-22 and KCL-22-IMR cells in a dose-dependent manner.
Mol Ther Oncolytics. 2021 Nov 20;23:560-570.
K1 cells
1 µM, 10 µM, 25 µM
24 hours
To evaluate the effect of BAY-293 on thyroid cancer cell viability, results showed that BAY-293 significantly reduced cell viability in a concentration-dependent manner.
Int J Mol Sci. 2025 Mar 13;26(6):2579.
FTC-133 cells
1 µM, 10 µM, 25 µM
24 hours
To evaluate the effect of BAY-293 on thyroid cancer cell viability, results showed that BAY-293 significantly reduced cell viability in a concentration-dependent manner.
Int J Mol Sci. 2025 Mar 13;26(6):2579.
8305C cells
1 µM, 10 µM, 25 µM
24 hours
To evaluate the effect of BAY-293 on thyroid cancer cell viability, results showed that BAY-293 significantly reduced cell viability in a concentration-dependent manner.
Int J Mol Sci. 2025 Mar 13;26(6):2579.
MIA PaCa-2
2.5 μM
24 hours
BAY-293 promoted phosphorylation of ERK and AKT in a dose-dependent manner and increased expression of cleaved PARP, suggesting potential apoptosis promotion via feedback regulation.
Acta Pharmacol Sin. 2022 Oct;43(10):2696-2708.
PANC-1
2.5 μM
72 hours
BAY-293 inhibited ERK phosphorylation, and a rebound in protein expression and phosphorylation levels was observed at 48 h (pERK) and 72 h (pAKT).
Acta Pharmacol Sin. 2022 Oct;43(10):2696-2708.
MIA PaCa-2
5 µM
4 days
Test the synergy of BAY-293 with 2-DG, showing synergistic effects.
Discov Oncol. 2022 Sep 1;13(1):84.
BH1522 cells
0.2 µM
BAY-293 inhibited proliferation and suppressed MYC activity in BH1522 cells.
Sci Rep. 2025 Jan 23;15(1):2893.
BH1406 NSCLC cells
1.12 µM
4 days
BAY-293 significantly inhibited the viability of BH1406 cells with an IC50 value of 1.12 µM.
Transl Lung Cancer Res. 2024 Nov 30;13(11):2987-2997.
BH1406 NSCLC cells
0.5 µM
72 hours
BAY-293 treatment significantly reduced the expression levels of SOS1 and MYC.
Transl Lung Cancer Res. 2024 Nov 30;13(11):2987-2997.
HT22 cells
2 μM
24 hours
After inhibiting SOS1, the expression level of FBL was significantly reduced, indicating that BAY-293 regulates FBL expression by inhibiting SOS1, thereby reducing the inflammatory response.
J Inflamm Res. 2024 Apr 11;17:2217-2231.
BAY-293 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
NOD/SCID mice
BCR-ABL-independent imatinib resistance model
Intraperitoneal injection
20 mg/kg
Once daily for 7 days
BAY-293 prolonged survival in a mouse model of BCR-ABL-independent resistance compared with saline or imatinib, showing significant efficacy.
Mol Ther Oncolytics. 2021 Nov 20;23:560-570.
BALB/c nude mice
ATC orthotopic model
Intraperitoneal injection
10 mg/kg, 50 mg/kg
2 weeks
To evaluate the antitumor effect of BAY-293 in an ATC orthotopic model, results showed that BAY-293 significantly improved pathological features and reduced tumor growth.
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