Elimusertib

Elimusertib (BAY-1895344) is a potent, orally active and selective ATR inhibitor with an IC₅₀ of 7 nM. Elimusertib has anti-tumor activity^[1][2]. Elimusertib can be used for the research of solid tumors and lymphomas^[3]. IC50 & Target: IC50: 7 nM (ATR)^[1] In Vitro: Elimusertib potently inhibits the proliferation of a broad spectrum of human tumor cell lines with a median IC₅₀ of 78 nM^[1].
Elimusertib potently suppresses hydroxyurea-induced H2AX phosphorylation (IC₅₀: 36 nM)^[1].
Elimusertib shows good selectivity against mTOR (ratio of IC₅₀ values: mTOR/ATR 61)^[3].
Elimusertib reveals high selectivity against other related kinases, such as DNA-PK (IC₅₀: 332 nM), ATM (IC₅₀: 1420 nM), and PI3K (IC₅₀: 3270 nM)^[3].
Elimusertib has potent antiproliferative activity against various cancer cell lines in vitro, 25 for example in the CRC cell lines HT-29 (IC₅₀: 160 nM) and LoVo (IC₅₀: 71 nM), and in the B-cell lymphoma cell line SU-DHL-8 (IC₅₀: 9 nM)^[3].
In Vivo: Elimusertib shows potent anti-tumor efficacy in monotherapy in a variety of xenograft models of ovarian and colorectal cancer, and causes complete tumor remission in mantle cell lymphoma models^[2].
Elimusertib (50 mg/kg; p.o.; b.i.d.; 3 days on/4 days off; for 11 days) exhibits strong antitumor efficacy in the ATM-mutated SU-DHL-8 (ATM K1964E) human GCB-DLBCL cell line derived xenograft model in mice^[3].
Elimusertib (20 mg/kg, and 10 mg/kg from day 14; p.o.; daily; 2 days on/5 days off; for 42 days) in combination with Carboplatin (40 mg/kg; i.p.; daily; 1 day on/6 days off) results in synergistic antitumor activity in the platinum-resistant ATM protein low expressing CR5038 human CRC PDX model in NOD/SCID mice^[3].
Elimusertib exhibits moderate oral bioavailability (rat 87%, dog 51%) following oral administration (rat and dog 0.6-1 mg/kg)^[3].
Elimusertib exhibits terminal elimination half-lives (mouse 0.17 h, rat 1.3 and, dog 1.0 h) due to plasma clearance (3.5, 1.2, and 0.79 L/h/kg respectively) following intravenous administration (mouse, rat and dog 0.3-0.5 mg/kg)^[3].