Elimusertib, also known as BAY-1895344, is an effective, orally active, selective ATR inhibitor with an IC50 of 7 nM. It exhibits antitumor activity[1][2]. Elimusertib effectively inhibits the proliferation of various human tumor cell lines, with a median IC50 value of 78 nM. Elimusertib also effectively inhibits hydroxyurea-induced H2AX phosphorylation (IC50: 36 nM)[1]. Elimusertib exhibits effective anti-proliferative activity in vitro against various cancer cell lines, such as in the CRC cell lines HT-29 (IC50: 160 nM) and LoVo (IC50: 71 nM), as well as in the B-cell lymphoma cell line SU-DHL-8 (IC50: 9 nM)[3].
Elimusertib 细胞实验
Cell Line
Concentration
Treated Time
Description
References
NB1
100 nM
2 hours
To investigate the effect of ALK signaling on ATR and CHK1 phosphorylation, results showed ALKAL2 stimulation increased CHK1 S280 phosphorylation.
Proc Natl Acad Sci U S A. 2024 Jan 2;121(1):e2315242121.
CLB-BAR
100 nM
2 hours
To investigate the effect of ALK signaling on ATR and CHK1 phosphorylation, results showed ALKAL2 stimulation increased CHK1 S280 phosphorylation.
Proc Natl Acad Sci U S A. 2024 Jan 2;121(1):e2315242121.
HCC1954-TDM1R
100 nM
48 hours
To evaluate the antiproliferative effect of elimusertib in combination with T-DXd, results showed that the combination significantly increased the expression of DNA damage marker pH2AX
J Exp Clin Cancer Res. 2024 Aug 21;43(1):236.
SUM190-TDM1R
100 nM
48 hours
To evaluate the antiproliferative effect of elimusertib in combination with T-DXd, results showed that the combination significantly increased the expression of DNA damage marker pH2AX and apoptosis marker cleaved PARP
J Exp Clin Cancer Res. 2024 Aug 21;43(1):236.
DMG cells
200 nM
24 hours
Evaluated the effect of ATR inhibition on DMG cells, showing significant increase in replication stress and DNA damage when combined with DHODH inhibitor BAY2402234.
Cancer Cell. 2022 Sep 12;40(9):957-972.e10.
CCHE-45 cells
500 nM melphalan + 50 nM elimusertib
8 hours
To assess the synergistic effects of melphalan and elimusertib combination on CPC cells, results showed significant changes in transcriptomic profiles, activating key biological processes such as DNA repair and apoptosis.
J Control Release. 2023 May;357:580-590.
CCHE-45 cells
50 nM
8 hours
To evaluate the transcriptomic effects of Elimusertib on CPC cells, results showed that Elimusertib alone caused upregulation of 236 genes and downregulation of 33 genes.
J Control Release. 2023 May;357:580-590.
Glioma sphere-forming cells (GSCs)
0.25 μM to 2.25 μM
72 hours
Evaluated the synergistic effect of TMZ and elimusertib, finding that MGMT-methylated GSCs exhibited synergy under combination treatment.
Neurooncol Adv. 2023 Dec 19;6(1):vdad165.
Glioma sphere-forming cells (GSCs)
10 nM–2 μM
3 days
Assessed the effect of ATR inhibitors on cell viability in GSCs, finding that MGMT-methylated GSCs were resistant to ATR inhibitor monotherapy but showed synergistic effects when combined with TMZ.
Neurooncol Adv. 2023 Dec 19;6(1):vdad165.
Elimusertib 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
CB17/SCID mice
ULMS patient-derived xenograft models
Oral gavage
20 mg/kg
Twice daily, 3 days on/4 days off
To evaluate the antitumor activity and survival prolongation effect of Elimusertib on ATRX-mutated uLMS PDX models. Results showed significant tumor growth inhibition (p<0.001) and prolonged median overall survival (PDX LEY-11: 12.5 vs. 42 days; PDX LEY-16: 33 vs. 60 days) compared to control.
Gynecol Oncol. 2023 Jan;168:157-165
Mouse
Alk-F1178S;Th-MYCN mouse neuroblastoma model
Oral
25 mg/kg
Twice daily for 14 days
To evaluate the efficacy of elimusertib monotherapy versus combination therapy with lorlatinib, results showed combination therapy led to complete tumor regression without relapse.
Proc Natl Acad Sci U S A. 2024 Jan 2;121(1):e2315242121.
Nude mice
HER2+ breast cancer xenograft models
Oral gavage
10 mg/kg
Twice daily for 3 consecutive days per week
To evaluate the antitumor effect of elimusertib in combination with T-DXd, results showed that the combination significantly enhanced the antitumor effect of T-DXd in TDM1R and TDXdR models
J Exp Clin Cancer Res. 2024 Aug 21;43(1):236.
NSG mice
Intracranial DMG xenograft model
Oral
200 nM
Once daily until euthanasia
Assessed the efficacy of ATR inhibitor elimusertib in combination with DHODH inhibitor BAY2402234, showing significant prolongation of survival in mice bearing DMG xenografts.
Cancer Cell. 2022 Sep 12;40(9):957-972.e10.
Mice
MYC-OE CPC genetic model
Intra-arterial injection
0.22 mg/kg
Single injection
To evaluate the survival impact of melphalan and elimusertib combination therapy in a CPC mouse model, results showed a significant extension in median survival (51 days vs 38.5 days in control).
J Control Release. 2023 May;357:580-590.
Nude mice
Intracranial glioma model
Oral gavage
50 mg/kg/day
3 days/week for 4 weeks
Assessed the in vivo efficacy of elimusertib combined with TMZ in MGMT-methylated tumors, showing that combination treatment significantly improved mouse survival.
Neurooncol Adv. 2023 Dec 19;6(1):vdad165.
Elimusertib 动物研究
Animal study
Elimusertib demonstrates effective antitumor efficacy as a monotherapy in various ovarian and colorectal cancer xenograft models, and leads to complete remission of tumors in mantle cell lymphoma models[2].
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