BAY-1895344

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

BAY-1895344 是一种有效的、选择性的、口服活性的 ATR 抑制剂，具有低纳摩尔效力；有效抑制广谱人类肿瘤细胞系的增殖，平均 IC50 为 78 nM；抑制羟基脲诱导的 H2AX 磷酸化，在多种异种移植模型中单一疗法中表现出强大的体内抗肿瘤功效。

BAY-1895344 is a potent, selective, orally active ATR inhibitor with low-nanomolar potency; potently inhibits the proliferation of a broad spectrum of human tumor cell lines with mean IC50 of 78 nM; inhibits hydroxyurea-induced H2AX phosphorylation, exhibits strong in vivo anti-tumor efficacy in monotherapy in a variety of xenograft models.Blood Cancer,Phase 1 Clinical(In Vitro):Elimusertib potently inhibits the proliferation of a broad spectrum of human tumor cell lines with a median IC50 of 78 nM.Elimusertib potently suppresses hydroxyurea-induced H2AX phosphorylation (IC50: 36 nM).Elimusertib shows good selectivity against mTOR (ratio of IC50 values: mTOR/ATR 61).Elimusertib reveals high selectivity against other related kinases, such as DNA-PK (IC50: 332 nM), ATM (IC50: 1420 nM), and PI3K (IC50: 3270 nM).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). (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.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.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.Elimusertib exhibits moderate oral bioavailability (rat 87%, dog 51%) following oral administration (rat and dog 0.6-1 mg/kg).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).

Elimusertib potently inhibits the proliferation of a broad spectrum of human tumor cell lines with a median IC50 of 78 nM.?Elimusertib potently suppresses hydroxyurea-induced H2AX phosphorylation (IC50: 36 nM).?Elimusertib shows good selectivity against mTOR (ratio of IC50 values: mTOR/ATR 61).Elimusertib reveals high selectivity against other related kinases, such as DNA-PK (IC50: 332 nM), ATM (IC50: 1420 nM), and PI3K (IC50: 3270 nM).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).

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.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.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.Elimusertib exhibits moderate oral bioavailability (rat 87%, dog 51%) following oral administration (rat and dog 0.6-1 mg/kg).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). Animal Model:Female C.B-17 SCID mice, SU-DHL-8 GCB-DLBCL xenograft model Dosage:50 mg/kgAdministration:Oral administration, b.i.d., 3 days on/4 days off, for 11 days Result:Inhibited tumor area.Animal Model:Male Wistar rats 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%), T1/2 (1.3 h).Animal Model:Female beagle dogs 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%), T1/2 (1.0 h).

BAY 1895344 | BAY1895344

Cell Cycle/DNA Damage

ATM/ATR

ATM/ATR

Cancer

Blood cancer

1876467-74-1

375.436

C20H21N7O

>98% (HPLC)

In Vitro:?DMSO : 5.4 mg/mL (14.38 mM)

CC1COCCN1C2=NC3=C(C=CN=C3C4=CC=NN4)C(=C2)C5=CC=NN5C

(R)-3-methyl-4-(4-(1-methyl-1H-pyrazol-5-yl)-8-(1H-pyrazol-5-yl)-1,7-naphthyridin-2-yl)morpholine

(-20℃)

With Ice Pack

≥ 2 years