Tesirine (Synonyms: SG3249) |
Catalog No.GC63216
One-Click Copy Product Info
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Tesirine is an antibody-drug conjugate (ADC) pyrrolobenzodiazepine (PBD) dimer payload.
Products are for research use only. Not for human use. We do not sell to patients.
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.
| Cell experiment [1]: | |
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Cell lines |
Lymphoma cell lines |
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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. |
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Reaction Conditions |
0-15nM; 96h |
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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]: | |
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Animal models |
Immunodeficiency mice, rat and cynomolgus monkey |
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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. |
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Dosage form |
1.5mg/kg; i.v. |
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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. |
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References: |
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| Cas No. | 1595275-62-9 | SDF | |
| Synonyms | SG3249 | ||
| Formula | C75H101N9O23 | M.Wt | 1496.65 |
| Solubility | DMSO : 200 mg/mL (133.63 mM; Need ultrasonic) | Storage | Store at -20°C, protect from light, stored under nitrogen |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 668.2 μL | 3.3408 mL | 6.6816 mL |
| 5 mM | 133.6 μL | 668.2 μL | 1.3363 mL |
| 10 mM | 66.8 μL | 334.1 μL | 668.2 μL |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
g
μL
Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)
Calculation results:
Working concentration: mg/ml;
Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )
Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL saline, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
- View current batch:
- Purity: >95.00% Appearance: A solid
- COA (Certificate of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 12 reference(s) in Google Scholar.)