Elimusertib (BAY-1895344) 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 可用于实体瘤和淋巴瘤的研究。
| 生物活性 | Elimusertib (BAY-1895344) is a potent, orally active and selectiveATRinhibitor with anIC50of 7 nM. Elimusertib has anti-tumor activity[1][2]. Elimusertib can be used for the research of solid tumors and lymphomas[3]. |
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体外研究
(In Vitro) | Elimusertib potently inhibits the proliferation of a broad spectrum of human tumor cell lines with a median IC50of 78 nM[1].
Elimusertib potently suppresses hydroxyurea-induced H2AX phosphorylation (IC50: 36 nM)[1].
Elimusertib shows good selectivity against mTOR (ratio of IC50values: 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].
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体内研究
(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].
| 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%), T1/2(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%), T1/2(1.0 h). |
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| 运输条件 | Room temperature in continental US; may vary elsewhere. |
| 储存方式 | | Powder | -20°C | 3 years | | 4°C | 2 years | | In solvent | -80°C | 6 months | | -20°C | 1 month |
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| 溶解性数据 | In Vitro: DMSO : 5.4 mg/mL(14.38 mM;Need ultrasonic) 配制储备液 | 1 mM | 2.6636 mL | 13.3181 mL | 26.6361 mL | | 5 mM | 0.5327 mL | 2.6636 mL | 5.3272 mL | | 10 mM | 0.2664 mL | 1.3318 mL | 2.6636 mL |
*请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。
储备液的保存方式和期限：-80℃, 6 months; -20℃, 1 month。-80℃ 储存时，请在 6 个月内使用，-20℃ 储存时，请在 1 个月内使用。 In Vivo: 请根据您的实验动物和给药方式选择适当的溶解方案。以下溶解方案都请先按照In Vitro方式配制澄清的储备液，再依次添加助溶剂： ——为保证实验结果的可靠性，澄清的储备液可以根据储存条件，适当保存；体内实验的工作液，建议您现用现配，当天使用；
以下溶剂前显示的百
分比是指该溶剂在您配制终溶液中的体积占比；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的方式助溶 1. 请依序添加每种溶剂： 0.5%CMC-Na/saline water Solubility: 4 mg/mL (10.65 mM); Suspended solution; Need ultrasonic and adjust pH to 3 with HCl 2. 请依序添加每种溶剂： 10% DMSO 90% (20%SBE-β-CDin saline) Solubility: 1.09 mg/mL (2.90 mM); Suspended solution; Need ultrasonic
此方案可获得 1.09 mg/mL (2.90 mM) 的均匀悬浊液，悬浊液可用于口服和腹腔注射。 以 1 mL 工作液为例，取 100 μL 10.9 mg/mL 的澄清 DMSO 储备液加到 900 μL20% 的 SBE-β-CD 生理盐水水溶液中，混合均匀。 3. 请依序添加每种溶剂： 10% DMSO 40%PEG300 5%Tween-80 45% saline Solubility: 0.89 mg/mL (2.37 mM); Suspended solution; Need ultrasonic
此方案可获得 0.89 mg/mL (2.37 mM) 的均匀悬浊液，悬浊液可用于口服和腹腔注射。 以 1 mL 工作液为例，取 100 μL 8.9 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀；向上述体系中加入50 μL Tween-80，混合均匀；然后继续加入 450 μL生理盐水定容至 1 mL。 *以上所有助溶剂都可在本网站选购。
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