Physicochemical Properties
| Molecular Formula | C72H85N19O18S5 |
| Molecular Weight | 1664.89 |
| Exact Mass | 1663.49 |
| Elemental Analysis | C, 51.94; H, 5.15; N, 15.99; O, 17.30; S, 9.63 |
| CAS # | 1393-48-2 |
| PubChem CID | 16129666 |
| Appearance | White to off-white solid powder |
| Density | 1.64 g/cm3 |
| Melting Point | 248-257°C (dec.) |
| Index of Refraction | 1.768 |
| LogP | 4.086 |
| Hydrogen Bond Donor Count | 17 |
| Hydrogen Bond Acceptor Count | 31 |
| Rotatable Bond Count | 12 |
| Heavy Atom Count | 114 |
| Complexity | 3940 |
| Defined Atom Stereocenter Count | 0 |
| SMILES | S1C([H])=C2C(N([H])C([H])(C(N([H])C(=C([H])C([H])([H])[H])C3=NC([H])(C([H])([H])S3)C(N([H])C([H])(C3=NC(=C([H])S3)C(N([H])C3([H])C([H])(C([H])([H])[H])OC(C4C([H])=C(C([H])(C([H])([H])[H])O[H])C5C([H])=C([H])C([H])(C([H])(C=5N=4)O[H])N([H])C([H])(C(N([H])C([H])(C([H])([H])[H])C(N([H])C(=C([H])[H])C(N([H])C([H])(C([H])([H])[H])C(N([H])C4(C1=N2)C([H])([H])C([H])([H])C(C1=NC(C(N([H])C(=C([H])[H])C(N([H])C(=C([H])[H])C(N([H])[H])=O)=O)=O)=C([H])S1)=NC4([H])C1=C([H])SC3=N1)=O)=O)=O)=O)C([H])(C([H])([H])[H])C([H])([H])C([H])([H])[H])=O)=O)C(C([H])([H])[H])(C([H])(C([H])([H])[H])O[H])O[H])=O)=O)C([H])(C([H])([H])[H])O[H])=O |
| InChi Key | NSFFHOGKXHRQEW-DVRIZHICSA-N |
| InChi Code | InChI=1S/C72H85N19O18S5/c1-14-26(3)47-63(105)78-30(7)57(99)75-28(5)56(98)76-31(8)58(100)91-72-19-18-40(66-85-43(22-111-66)59(101)77-29(6)55(97)74-27(4)54(73)96)81-52(72)42-21-112-67(83-42)49(34(11)109-69(107)41-20-37(32(9)92)36-16-17-39(79-47)51(95)50(36)80-41)89-60(102)44-24-113-68(86-44)53(71(13,108)35(12)94)90-62(104)45-23-110-65(84-45)38(15-2)82-64(106)48(33(10)93)88-61(103)46-25-114-70(72)87-46/h15-17,20-22,24-26,30-35,39,45,47-49,51-53,79,92-95,108H,4-6,14,18-19,23H2,1-3,7-13H3,(H2,73,96)(H,74,97)(H,75,99)(H,76,98)(H,77,101)(H,78,105)(H,82,106)(H,88,103)(H,89,102)(H,90,104)(H,91,100)/b38-15+ |
| Chemical Name | N-[3-[(3-amino-3-oxoprop-1-en-2-yl)amino]-3-oxoprop-1-en-2-yl]-2-[(11Z)-37-butan-2-yl-18-(2,3-dihydroxybutan-2-yl)-11-ethylidene-59-hydroxy-8,31-bis(1-hydroxyethyl)-26,40,46-trimethyl-43-methylidene-6,9,16,23,28,38,41,44,47-nonaoxo-27-oxa-3,13,20,56-tetrathia-7,10,17,24,36,39,42,45,48,52,58,61,62,63,64-pentadecazanonacyclo[23.23.9.329,35.12,5.112,15.119,22.154,57.01,53.032,60]tetrahexaconta-2(64),4,12(63),19(62),21,29(61),30,32(60),33,51,54,57-dodecaen-51-yl]-1,3-thiazole-4-carboxamide |
| Synonyms | NSC-170365; NSC170365;NSC 170365; |
| HS Tariff Code | 2934.99.03.00 |
| Storage |
Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment, 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 | Thiostrepton (0.01-1000 μM; 48 hours) suppresses cell viability in A2780 and HEC-1A[2]. |
| ln Vivo | Thiostrepton (i.p. ; 17 mg/kg) decreases Ewing's sarcoma (EWS) cell carcinogenicity. The tumor volumes of control mice have increased approximately six times since the start of treatment, whereas the tumor volumes of mice treated with Thiostrepton have increased only approximately 1.7 times, showing a ~3.5-fold reduction, in comparison to controls[3]. |
| Cell Assay |
Cell Line: A2780 and HEC-1A cells Concentration: 0.01, 0.1, 1, 10, 100, 1000 μM Incubation Time: 48 hours Result: The IC50s are 1.10 μM in A2780 and 2.22 μM in HEC-1A, respectively. |
| Animal Protocol |
Animal Model: Athymic (BALB/c nu/nu) nude mice bearing A4573 cells[3] Dosage: 17 mg/kg Administration: Administered i.p. Result: Treatment inhibited the growth of EWS-derived tumors in vivo. |
| References |
[1]. A combat with the YAP/TAZ-TEAD oncoproteins for cancer therapy. Theranostics. 2020 Feb 18;10(8):3622-3635. [2]. Targeting of mutant p53-induced FoxM1 with Thiostrepton induces cytotoxicity and enhances carboplatin sensitivity in cancer cells. Oncotarget. 2014 Nov 30;5(22):11365-80. [3]. The dual inhibitory effect of Thiostrepton on FoxM1 and EWS/FLI1 provides a novel therapeutic option for Ewing's sarcoma. Int J Oncol. 2013 Sep;43(3):803-12. |
| Additional Infomation |
Thiostrepton is a natural cyclic oligopeptide antibiotic, derived from several strains of streptomycetes including Streptomyces azureus and Streptomyces laurentii. Thiostrepton is a natural product of the ribosomally synthesized and post-translationally modified peptide class. Bryamycin has been reported in Streptomyces albidoflavus, Streptomyces aureus, and other organisms with data available. Thiostrepton is a naturally-occurring, sulfur-rich, cyclic oligopeptide antibiotic of the thiopeptide class, and an irreversible inhibitor of the mitochondrial thioredoxin-dependent peroxide reductase (peroxiredoxin-3; PRX3; antioxidant protein 1; AOP-1), with potential antineoplastic activity. Upon intrapleural administration, thiostrepton irreversibly binds to and inhibits the activity of PRX3. This inhibits the peroxidase activity of the thioredoxin reductase 2 (TXNRD2)-thioredoxin-2 (TRX2)-PRX3 antioxidant signaling network within the mitochondria, which may result in the accumulation of hydrogen peroxide and lead to tumor cell death. PRX3 is upregulated in cancer cells and plays an important role in the regulation of the oxidative stress pathways. One of the CYCLIC PEPTIDES from Streptomyces that is active against gram-positive bacteria. In veterinary medicine, it has been used in mastitis caused by gram-negative organisms and in dermatologic disorders. See also: Thiostrepton (annotation moved to). |
Solubility Data
| Solubility (In Vitro) | DMSO : 100~125 mg/mL ( 60.06~75.08 mM ) |
| Solubility (In Vivo) |
Solubility in Formulation 1: 5 mg/mL (3.00 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication. 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 (3.00 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: ≥ 4.17 mg/mL (2.50 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 41.7 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. Solubility in Formulation 4: 5% DMSO+ 40% PEG300+ 5% Tween 80+ 50% ddH2O: 1.25mg/ml (0.75mM) (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 0.6006 mL | 3.0032 mL | 6.0064 mL | |
| 5 mM | 0.1201 mL | 0.6006 mL | 1.2013 mL | |
| 10 mM | 0.0601 mL | 0.3003 mL | 0.6006 mL |