Tesirine
(Synonyms: SG3249) 目录号 : GC63216Tesirine 是一种抗体药物偶联物（ADC）的吡咯苯并二氮杂卓（PBD）二聚体有效载荷。
Cas No.:1595275-62-9
Sample solution is provided at 25 µL, 10mM.
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Tesirine is an antibody-drug conjugate (ADC) pyrrolobenzodiazepine (PBD) dimer payload[1]. PBD dimers are highly efficient DNA minor groove cross-linking agents with potent cytotoxicity[2]. Tesirine combines potent antitumor activity with desirable physicochemical properties, such as favorable hydrophobicity and improved conjugation characteristics, and is usually used in the research of various cancers[3-5].
In vitro, treatment of lymphoma cells with Loncastuximab Tesirine (0-15nM) for 96h demonstrates potent cytotoxicity in B-cell lymphoma cell lines, with a median IC50 of 4.1pM and a negative correlation between IC50 values and CD19 surface density. While in T-cell lymphoma cell lines, the median IC50 is significantly higher at 3.5nM[6].
In vivo, single doses of Loncastuximab Tesirine(1.5mg/kg; i.v.) demonstrated highly potent, dose-dependent antitumor activity in various several subcutaneous and disseminated human tumor models, and showed excellent stability and tolerability in pharmacokinetic studies in rats and monkeys, with DNA crosslinks and g-H2AX DNA damage response detected in tumors but not in peripheral blood mononuclear cells by 24 hours after administration[7].
References:
[1] Tiberghien, A. C., Levy, J. N., Masterson, L. A., Patel, N. V., Adams, L. R., Corbett, S., Williams, D. G., Hartley, J. A., & Howard, P. W. (2016). Design and Synthesis of Tesirine, a Clinical Antibody-Drug Conjugate Pyrrolobenzodiazepine Dimer Payload. ACS medicinal chemistry letters, 7(11), 983–987.
[2] Hartley, J. A., Flynn, M. J., Bingham, J. P., Corbett, S., Reinert, H., Tiberghien, A., Masterson, L. A., Antonow, D., Adams, L., Chowdhury, S., Williams, D. G., Mao, S., Harper, J., Havenith, C. E. G., Zammarchi, F., Chivers, S., van Berkel, P. H., & Howard, P. W. (2018). Pre-clinical pharmacology and mechanism of action of SG3199, the pyrrolobenzodiazepine (PBD) dimer warhead component of antibody-drug conjugate (ADC) payload tesirine. Scientific reports, 8(1), 10479.
[3] Lee A. (2021). Loncastuximab Tesirine: First Approval. Drugs, 81(10), 1229–1233.
[4] Rudin, C. M., Pietanza, M. C., Bauer, T. M., Ready, N., Morgensztern, D., Glisson, B. S., Byers, L. A., Johnson, M. L., Burris, H. A., 3rd, Robert, F., Han, T. H., Bheddah, S., Theiss, N., Watson, S., Mathur, D., Vennapusa, B., Zayed, H., Lally, S., Strickland, D. K., Govindan, R., … SCRX16-001 investigators (2017). Rovalpituzumab tesirine, a DLL3-targeted antibody-drug conjugate, in recurrent small-cell lung cancer: a first-in-human, first-in-class, open-label, phase 1 study. The Lancet. Oncology, 18(1), 42–51.
[5] Juárez-Salcedo, L. M., Nimkar, S., Corazón, A. M., & Dalia, S. (2024). Loncastuximab Tesirine in the Treatment of Relapsed or Refractory Diffuse Large B-Cell Lymphoma. International journal of molecular sciences, 25(14), 7580.
[6] Tarantelli, C., Wald, D., Munz, N., Spriano, F., Bruscaggin, A., Cannas, E., Cascione, L., Gaudio, E., Arribas, A. J., Manjappa, S., Golino, G., Scalise, L., Cacciapuoti, M. T., Zucca, E., Stathis, A., Inghirami, G., Van Berkel, P. H., Rossi, D., Caimi, P. F., Zammarchi, F., … Bertoni, F. (2024). Targeting CD19-positive lymphomas with the antibodydrug conjugate loncastuximab tesirine: preclinical evidence of activity as a single agent and in combination therapy. Haematologica, 109(10), 3314–3326.
[7] Zammarchi, F., Corbett, S., Adams, L., Tyrer, P. C., Kiakos, K., Janghra, N., Marafioti, T., Britten, C. E., Havenith, C. E. G., Chivers, S., D'Hooge, F., Williams, D. G., Tiberghien, A., Howard, P. W., Hartley, J. A., & van Berkel, P. H. (2018). ADCT-402, a PBD dimer-containing antibody drug conjugate targeting CD19-expressing malignancies. Blood, 131(10), 1094–1105.
Tesirine 是一种抗体药物偶联物（ADC）的吡咯苯并二氮杂卓（PBD）二聚体有效载荷[1]。PBD 二聚体是高效的 DNA 小槽交联剂，具有强大的细胞毒性[2]。Tesirine 结合了强大的抗肿瘤活性和理想的物理化学特性，例如良好的疏水性和改进的偶联特性，通常用于多种癌症的研究[3-5]。
在体外实验中，用 Loncastuximab Tesirine(0-15nM) 处理淋巴瘤细胞 96 小时，在 B 细胞淋巴瘤细胞系中表现出强烈的细胞毒性，中位 IC50 为 4.1pM，且 IC50 值与细胞表面 CD19 密度呈负相关。然而在 T 细胞淋巴瘤细胞系中，Loncastuximab Tesirine的IC50中位数较高，为3.5nM[6]。
在体内实验中，Loncastuximab Tesirine（1.5mg/kg；静脉注射）在多种皮下和弥散性人类肿瘤模型中表现出高度有效的、剂量依赖性的抗肿瘤活性，并且在大鼠和猴子的药代动力学研究中显示出良好的稳定性和耐受性。在给药后 24 小时内，肿瘤中检测到 DNA 交联和 γ-H2AX DNA 损伤反应，而外周血单个核细胞中未检测到[7]。
| Cell experiment [1]: | |
Cell lines | Lymphoma cell lines |
Preparation Method | Lymphoma cell lines were cultured according to the recommended conditions. All media were supplemented with fetal bovine serum (10% or 20%) and penicillin-streptomycin-neomycin (≈5,000 units penicillin, 5mg streptomycin, and 10mg neomycin/mL). Cells were exposed to Loncastuximab Tesirine for 96 hours with different concentrations (0-15nM) and assayed by MTT. Absolute cell surface CD19 expression was determined via quantification of the antigen on the surface of lymphoma cell lines using Quantum Simply Cellular anti-human IgG beads. |
Reaction Conditions | 0-15nM; 96h |
Applications | Loncastuximab Tesirine demonstrates potent cytotoxicity in B-cell lymphoma cell lines, with a median IC50 of 4.1pM and a negative correlation between IC50 values and CD19 surface density, while in T-cell lymphoma cell lines, the median IC50 is significantly higher at 3.5nM. |
| Animal experiment [2]: | |
Animal models | Immunodeficiency mice, rat and cynomolgus monkey |
Preparation Method | Ramos, Daudi, and WSU-DLCL2 xenografts were established in 8- to 10-week-old female Fox Chase severe combined immunodeficiency by implanting 107 cells subcutaneously (SC) into their flanks. When group mean tumor volumes reached approximately 116 to 132mm3, mice were randomly allocated into groups to receive Loncastuximab Tesirine(1.5mg/kg; i.v.) or vehicle. Each animal was euthanized when its tumor reached the end point volume or at study end. Male Crl:CD(SD) rats and male and female purpose-bred Cynomolgus monkeys were dosed IV with Tesirine (1.5mg/kg; i.v.). Blood was collected from tail veins at specified time points; serum was isolated and stored at 280°C. |
Dosage form | 1.5mg/kg; i.v. |
Applications | Loncastuximab Tesirine demonstrated highly potent, dose-dependent antitumor activity in various several subcutaneous and disseminated human tumor models, and showed excellent stability and tolerability in pharmacokinetic studies in rats and monkeys. |
References: | |
| Cas No. | 1595275-62-9 | SDF | |
| 别名 | SG3249 | ||
| 分子式 | C75H101N9O23 | 分子量 | 1496.65 |
| 溶解度 | DMSO : 200 mg/mL (133.63 mM; Need ultrasonic) | 储存条件 | Store at -20°C, protect from light, stored under nitrogen |
| 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 | 0.6682 mL | 3.3408 mL | 6.6816 mL |
| 5 mM | 0.1336 mL | 0.6682 mL | 1.3363 mL |
| 10 mM | 0.0668 mL | 0.3341 mL | 0.6682 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。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Quality Control & SDS
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- Purity: >98.00%
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