Elimusertib (BAY 1895344) hydrochloride 是一种有效、可口服、选择性的ATR抑制剂，IC50值为 7 nM，具有抗肿瘤活性。Elimusertib hydrochloride 可用于实体瘤和淋巴瘤的研究。

Elimusertib (BAY 1895344) hydrochloride is a potent, orally active and selective ATR inhibitor with an IC 50 of 7 nM. Elimusertib hydrochloride has anti-tumor activity [1] [2]. Elimusertib hydrochloride can be used for the research of solid tumors and lymphomas [3].

Elimusertib hydrochloride potently inhibits the proliferation of a broad spectrum of human tumor cell lines with a median IC 50 of 78 nM [1]. Elimusertib hydrochloride potently suppresses hydroxyurea-induced H2AX phosphorylation (IC 50 : 36 nM) [1]. Elimusertib hydrochloride shows good selectivity against mTOR (ratio of IC 50 values: mTOR/ATR 61) [3]. Elimusertib hydrochloride reveals high selectivity against other related kinases, such as DNA-PK (IC 50 : 332 nM), ATM (IC 50 : 1420 nM), and PI3K (IC 50 : 3270 nM) [3]. Elimusertib hydrochloride has potent antiproliferative activity against various cancer cell lines in vitro, 25 for example in the CRC cell lines HT-29 (IC 50 : 160 nM) and LoVo (IC 50 : 71 nM), and in the B-cell lymphoma cell line SU-DHL-8 (IC 50 : 9 nM) [3].

Elimusertib hydrochloride 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 hydrochloride (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 hydrochloride (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 hydrochloride exhibits moderate oral bioavailability (rat 87%, dog 51%) following oral administration (rat and dog 0.6-1 mg/kg) [3]. Elimusertib hydrochloride 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]. Animal Model: Female C.B-17 SCID mice, SU-DHL-8 GCB-DLBCL xenograft model [3] Dosage: 50 mg/kg Administration: Oral administration, b.i.d., 3 days on/4 days off, for 11 days Result: Inhibited tumor area. Animal Model: Male Wistar rats [3] Dosage: 0.3-0.5 mg/kg for i.v.; 0.6-1 mg/kg for oral (Pharmacokinetic Analysis) Administration: Intravenous injection and oral administration Result: Oral bioavailability (87%), T 1/2 (1.3 h). Animal Model: Female beagle dogs [3] Dosage: 0.3-0.5 mg/kg for i.v.; 0.6-1 mg/kg for oral (Pharmacokinetic Analysis) Administration: Intravenous injection and oral administration Result: Oral bioavailability (51%), T 1/2 (1.0 h).

C20H22ClN7O

411.89

(< 1 mg/ml refers to the product slightly soluble or insoluble )
Powder: -20°C for 3 years
In solvent: -80°C for 2 years