TAS1553是一种小分子蛋白-蛋白相互作用抑制剂，能有效抑制核糖核苷酸还原酶（RNR）的活性。TAS1553干扰DNA复制过程并减少细胞内脱氧腺苷三磷酸（dATP）的水平，最终诱导细胞凋亡。
Cas No.:2166023-31-8
Sample solution is provided at 25 µL, 10mM.
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TAS1553 is a small-molecule protein-protein interaction inhibitor that effectively suppresses the activity of ribonucleotide reductase (RNR). By disrupting the DNA replication process and reducing intracellular deoxyadenosine triphosphate (dATP) levels, TAS1553 ultimately induces apoptosis[1].
In vitro, treatment of human cancer cell lines (HCC38 and MV-4-11) with TAS1553 (0.228–10μmol/L) for 30 minutes to 24 hours significantly depletes the intracellular dATP pool, induces DNA replication stress and replication fork stalling, and leads to apoptotic cell death[1].
In vivo, oral administration of TAS1553 (50–400mg/kg) once daily for 14–21 days in female NOD/SCID mice bearing MV-4-11 xenografts significantly suppresses tumor growth and promotes tumor regression. This is accompanied by reduced intratumoral dATP levels and activation of replication stress and apoptotic pathways [1].
References:
[1] Ueno H, Hoshino T, Yano W, et al. TAS1553, a small molecule subunit interaction inhibitor of ribonucleotide reductase, exhibits antitumor activity by causing DNA replication stress. Commun Biol. 2022 Jun 9;5(1):571.
TAS1553是一种小分子蛋白-蛋白相互作用抑制剂，能有效抑制核糖核苷酸还原酶（RNR）的活性。TAS1553干扰DNA复制过程并减少细胞内脱氧腺苷三磷酸（dATP）的水平，最终诱导细胞凋亡[1]。
在体外，TAS1553（0.228–10μmol/L）处理人癌症细胞系（如HCC38和MV-4-11）30分钟至24小时，TAS1553显著降低细胞内脱氧腺苷三磷酸（dATP）库，并诱导DNA复制应激及复制叉停滞，最终导致细胞凋亡[1]。
在体内，TAS1553（50–400mg/kg）每日一次口服给药，用于处理携带MV-4-11异种移植瘤的雌性NOD/SCID小鼠，持续14-21天。TAS1553显著抑制肿瘤生长并诱导肿瘤消退，同时降低肿瘤内dATP库并激活复制应激与凋亡通路[1]。
| Cell experiment [1]: | |
Cell lines | Human cancer cell lines (HCC38 breast cancer, MV-4-11 acute myelogenous leukemia) |
Preparation Method | Cells were maintained in RPMI-1640 or DMEM supplemented with 10% fetal bovine serum (FBS) at 37°C, 5% CO₂. Cells were treated with TAS1553 at concentrations ranging from 0.228 to 10μmol/L for 30 minutes to 24 hours. |
Reaction Conditions | 0.228–10μmol/L; 30min–24h |
Applications | TAS1553 significantly reduced the intracellular dATP pool by disrupting the protein-protein interaction between RNR subunits R1 and R2, leading to DNA replication stress and replication fork stalling. This was accompanied by phosphorylation of Chk1 (Ser345) and RPA2 (Ser4/Ser8, Thr21) within 2 hours. TAS1553 induced apoptosis via caspase-3/7 activation and PARP cleavage, with efficacy strongly correlated with SLFN11 expression levels. |
| Animal experiment [1]: | |
Animal models | F344/NJcl-mu/rnu rats bearing MV-4-11 xenografts, BALB/cAJcl-nu/nu mice bearing HCC38 xenografts, and B6N-Tyrc-Brd/BrdCrCrl mice with systemic MLL-AF9-driven acute myelogenous leukemia (AML). |
Preparation Method | Rats and mice were subcutaneously implanted with tumor cells or intravenously inoculated with AML cells. TAS1553 was administered orally once daily at doses of 50–400mg/kg for 14–21 days. For pharmacodynamic studies, tumors were collected at 1, 2, and 4 hours after a single oral dose. |
Dosage form | 50–400mg/kg; p.o.; Once daily for 14–21 days |
Applications | TAS1553 administration significantly suppressed tumor growth in MV-4-11 xenografts and induced complete tumor regression at 400mg/kg. TAS1553 reduced intratumoral dATP pools within 1–2 hours, triggered DNA replication stress (phospho-Chk1 elevation), and activated apoptosis (cleaved PARP and caspase-3). In the systemic AML model, TAS1553 (100mg/kg) extended median survival by 34.8%. Body weight remained stable, indicating tolerability. |
References: | |
| Cas No. | 2166023-31-8 | SDF | Download SDF |
| 分子式 | C20H20ClFN4O5S | 分子量 | 482.91 |
| 溶解度 | DMSO : 100 mg/mL (207.08 mM; Need ultrasonic) | 储存条件 | Store at -20°C |
| General tips | 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°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.0708 mL | 10.3539 mL | 20.7078 mL |
| 5 mM | 414.2 μL | 2.0708 mL | 4.1416 mL |
| 10 mM | 207.1 μL | 1.0354 mL | 2.0708 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
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Quality Control & SDS
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- Purity: >98.00% Appearance: A solid
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