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Tesirine (SG-3249; SG3249), cathepsin B-cleavable valine-alanine pyrrolobenzodiazepine (PBD) dimer used as an antibody-drug conjugate (ADC) payload; Tesirine was designed to combine the potent antitumor activity with desirable physicochemical properties such as favorable hydrophobicity and improved conjugation characteristics. Rovalpituzumab tesirine is a first-in-class ADC directed against delta-like protein 3 (DLL3), a novel target identified in tumour-initiating cells and expressed in small-cell lung cancer.
Physicochemical Properties
| Molecular Formula | C75H101N9O23 |
| Molecular Weight | 1496.6510 |
| Exact Mass | 1495.701 |
| CAS # | 1595275-62-9 |
| PubChem CID | 73672523 |
| Appearance | White to light yellow solid powder |
| Density | 1.3±0.1 g/cm3 |
| Boiling Point | 1428.0±65.0 °C at 760 mmHg |
| Flash Point | 817.4±34.3 °C |
| Vapour Pressure | 0.0±0.3 mmHg at 25°C |
| Index of Refraction | 1.601 |
| LogP | -0.6 |
| Hydrogen Bond Donor Count | 5 |
| Hydrogen Bond Acceptor Count | 24 |
| Rotatable Bond Count | 49 |
| Heavy Atom Count | 107 |
| Complexity | 2970 |
| Defined Atom Stereocenter Count | 5 |
| SMILES | CC1=CN2[C@@H](C1)C=NC3=CC(=C(C=C3C2=O)OC)OCCCCCOC4=C(C=C5C(=C4)N([C@H]([C@@H]6CC(=CN6C5=O)C)O)C(=O)OCC7=CC=C(C=C7)NC(=O)[C@H](C)NC(=O)[C@H](C(C)C)NC(=O)CCOCCOCCOCCOCCOCCOCCOCCOCCNC(=O)CCN8C(=O)C=CC8=O)OC |
| InChi Key | HKGATZAPXCCEJR-OWRSNIELSA-N |
| InChi Code | InChI=1S/C75H101N9O23/c1-49(2)69(80-66(86)18-23-97-25-27-99-29-31-101-33-35-103-37-38-104-36-34-102-32-30-100-28-26-98-24-19-76-65(85)17-20-81-67(87)15-16-68(81)88)71(90)78-52(5)70(89)79-54-13-11-53(12-14-54)48-107-75(94)84-59-44-64(62(96-7)42-57(59)73(92)83-47-51(4)40-60(83)74(84)93)106-22-10-8-9-21-105-63-43-58-56(41-61(63)95-6)72(91)82-46-50(3)39-55(82)45-77-58/h11-16,41-47,49,52,55,60,69,74,93H,8-10,17-40,48H2,1-7H3,(H,76,85)(H,78,90)(H,79,89)(H,80,86)/t52-,55-,60-,69-,74-/m0/s1 |
| Chemical Name | [4-[[(2S)-2-[[(2S)-2-[3-[2-[2-[2-[2-[2-[2-[2-[2-[3-(2,5-dioxopyrrol-1-yl)propanoylamino]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]propanoylamino]-3-methylbutanoyl]amino]propanoyl]amino]phenyl]methyl (6S,6aS)-3-[5-[[(6aS)-2-methoxy-8-methyl-11-oxo-6a,7-dihydropyrrolo[2,1-c][1,4]benzodiazepin-3-yl]oxy]pentoxy]-6-hydroxy-2-methoxy-8-methyl-11-oxo-6a,7-dihydro-6H-pyrrolo[2,1-c][1,4]benzodiazepine-5-carboxylate |
| HS Tariff Code | 2934.99.9001 |
| Storage |
Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: (1). This product requires protection from light (avoid light exposure) during transportation and storage.(2). Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture. |
| Shipping Condition | Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs) |
Biological Activity
| ln Vitro | The release warhead part of the Tesirine ADC payload is Tesirine (SG3199). With IC50 values of 150 pM, 20 pM, 1 nM, and 320 pM, respectively, tesirine suppresses the growth of K562, NCIN87, BT474, and SKBR3 cancer cells[1]. |
| References |
[1]. Design and Synthesis of Tesirine, a Clinical Antibody-Drug Conjugate Pyrrolobenzodiazepine Dimer Payload. ACS Med Chem Lett. 2016;7(11):983-987. Published 2016 May 24. [2]. Pre-clinical pharmacology and mechanism of action of SG3199, the pyrrolobenzodiazepine (PBD) dimer warhead component of antibody-drug conjugate (ADC) payload tesirine. Sci Rep. 2018;8(1):10479. Published 2018 Jul 11. |
Solubility Data
| Solubility (In Vitro) | DMSO : ~200 mg/mL (~133.63 mM) |
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 5 mg/mL (3.34 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 50.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: 5 mg/mL (3.34 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 50.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 3: ≥ 5 mg/mL (3.34 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 50.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 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 |