| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg | |||
| 100mg | |||
| Other Sizes |
| Targets |
SG2057 targets DNA by binding sequence-selectively in the minor groove. As a PBD dimer, it forms covalent DNA interstrand cross-links (ICLs) and intrastrand cross-linked adducts, which prevent DNA replication and transcription, leading to cell death. This mechanism classifies SG2057 as a DNA alkylator/crosslinker.
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| ln Vitro |
SG2057 exhibits static differential external cytotoxicity, with an average GI50 of 212 pM, against a panel of human tumor cell lines. DNA interstrand cross-links can be effectively formed in cells by SG2057, and these cross-links persist for 48 hours [1].
SG2057 demonstrates potent in vitro cytotoxicity against a panel of human tumor cell lines with a mean GI50 of 212 pM. It is highly efficient at producing DNA interstrand cross-links in cells, which form rapidly and persist over a 48-hour period. The compound shows multilog differential cytotoxicity, indicating potent activity at sub-nanomolar concentrations across multiple cancer cell types. |
| ln Vivo |
In human xenograft tumor models, SG2057 (5-60 μg/kg; i.v.) demonstrates dose-dependent anti-activity [1].
SG2057 exhibits significant in vivo antitumor activity in various xenograft models. Cures were obtained in a LOX-IMVI melanoma model following a single administration. Dose-dependent activity, including regression responses, was observed in SKOV-3 ovarian and HL-60 promyelocytic leukemia models following repeat dose schedules. In the advanced stage LS174T model, SG2057 administered as a single dose or in repeat dose schedules was superior to irinotecan. |
| Enzyme Assay |
DNA interstrand cross-linking efficiency is assessed using purified plasmid DNA (e.g., pBR322) incubated with SG2057 at various concentrations. The formation of cross-linked DNA is analyzed by agarose gel electrophoresis, where cross-linked species migrate more slowly than uncross-linked DNA. Thermal denaturation and renaturation assays can also be used to quantify cross-linking, with the percentage of cross-linked DNA determined by the ratio of renaturable to total DNA. Binding to the DNA minor groove is confirmed by circular dichroism spectroscopy or footprinting assays.
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| Cell Assay |
Cytotoxicity is evaluated using a panel of human tumor cell lines including LOX-IMVI melanoma, SKOV-3 ovarian, HL-60 promyelocytic leukemia, and LS174T colorectal carcinoma cells. Cells are exposed to SG2057 at various concentrations for 72-96 hours, and cell viability is measured using standard assays such as MTT, XTT, or sulforhodamine B (SRB). The GI50 values are calculated from dose-response curves. DNA cross-linking in cells is assessed using the alkaline comet assay or pulsed-field gel electrophoresis to detect interstrand cross-links.
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| Animal Protocol |
Animal/Disease Models: Female NCr nude mice were injected with SKOV-3 cells [1]. 5μg/kg, 10μg/kg, 20μg/kg, 30μg/kg, 40μg/kg, 50μg/kg, 60μg/kg
Route of Administration: iv; one time/day, once weekly or every four days Experimental Results: Demonstrated significant resistance tumor activity. SG2057 is administered intravenously in murine xenograft models. In the LOX-IMVI melanoma model, a single administration of SG2057 produced cures. In SKOV-3 ovarian and HL-60 leukemia models, repeat dose schedules (e.g., daily or every other day for multiple cycles) are used to evaluate dose-dependent activity and tumor regression. In the advanced stage LS174T model, SG2057 is compared to irinotecan, with SG2057 showing superior efficacy. Tumor volumes are measured twice weekly, and body weight is monitored for toxicity. |
| ADME/Pharmacokinetics |
SG2057 has a molecular weight of 584.66 and molecular formula C33H36N4O6. It is soluble in DMSO but not in water. Powder formulations are stable at -20°C for up to 3 years, and in solvent at -80°C for 1 year. Shipping is typically performed with blue ice or at ambient temperature. The compound should be protected from light and stored under nitrogen for long-term stability. Pharmacokinetic studies indicate rapid clearance and persistence of DNA cross-links over 48 hours.
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| Toxicity/Toxicokinetics |
Preclinical toxicity studies in animal models indicate that SG2057 has a manageable safety profile at therapeutic doses, with the primary toxicity being myelosuppression, consistent with DNA-damaging agents. The compound shows dose-dependent antitumor activity with regression responses observed in multiple models. Body weight monitoring in animal studies is used as a general indicator of tolerability. At higher doses, gastrointestinal toxicity may occur. The therapeutic window is defined by the balance between antitumor efficacy and bone marrow suppression.
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| References | |
| Additional Infomation |
SG2057 (also known as DRG16) is a pyrrolobenzodiazepine (PBD) dimer connected by a pentyldioxy linkage. It selectively binds to the minor groove of DNA and forms interstrand and intrastrand cross-linked adducts. The compound has demonstrated superior in vivo activity compared to SG2000. SG2057 is currently an investigational antitumor agent developed by Spirogen Ltd, and is used primarily in preclinical cancer research to study DNA crosslinking mechanisms and PBD dimer pharmacology.
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| Molecular Formula |
C33H36N4O6
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|---|---|
| Molecular Weight |
584.66
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| Exact Mass |
584.263
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| CAS # |
260417-62-7
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| PubChem CID |
9938287
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| Appearance |
White to light yellow solid powder
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| Density |
1.3±0.1 g/cm3
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| Boiling Point |
820.0±65.0 °C at 760 mmHg
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| Flash Point |
449.7±34.3 °C
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| Vapour Pressure |
0.0±3.0 mmHg at 25°C
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| Index of Refraction |
1.647
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| LogP |
2.75
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
8
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| Rotatable Bond Count |
10
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| Heavy Atom Count |
43
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| Complexity |
1050
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| Defined Atom Stereocenter Count |
2
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| SMILES |
COC1=C(C=C2C(=C1)C(=O)N3CC(=C)C[C@H]3C=N2)OCCCCCOC4=C(C=C5C(=C4)N=C[C@@H]6CC(=C)CN6C5=O)OC
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| InChi Key |
KYNCKSRRIFFPJS-GOTSBHOMSA-N
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| InChi Code |
InChI=1S/C33H36N4O6/c1-20-10-22-16-34-26-14-30(28(40-3)12-24(26)32(38)36(22)18-20)42-8-6-5-7-9-43-31-15-27-25(13-29(31)41-4)33(39)37-19-21(2)11-23(37)17-35-27/h12-17,22-23H,1-2,5-11,18-19H2,3-4H3/t22-,23-/m0/s1
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| Chemical Name |
(6aS)-3-[5-[[(6aS)-2-methoxy-8-methylidene-11-oxo-7,9-dihydro-6aH-pyrrolo[2,1-c][1,4]benzodiazepin-3-yl]oxy]pentoxy]-2-methoxy-8-methylidene-7,9-dihydro-6aH-pyrrolo[2,1-c][1,4]benzodiazepin-11-one
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| Synonyms |
SG 2057; SG2057; SG2057
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| HS Tariff Code |
2934.99.9001
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| 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 (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)
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| Solubility (In Vitro) |
DMSO : ~100 mg/mL (~171.04 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (4.28 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 25.0 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: ≥ 2.5 mg/mL (4.28 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 25.0 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 | 1.7104 mL | 8.5520 mL | 17.1040 mL | |
| 5 mM | 0.3421 mL | 1.7104 mL | 3.4208 mL | |
| 10 mM | 0.1710 mL | 0.8552 mL | 1.7104 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution 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 stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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