| Size | Price | Stock | Qty |
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| 1mg |
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| 10mg | |||
| Other Sizes |
| Targets |
SG3199 targets DNA as a pyrrolobenzodiazepine (PBD) dimer that binds sequence-selectively in the minor groove and forms covalent DNA interstrand cross-links. It is classified as a DNA alkylator/crosslinker and an ADC cytotoxin. The compound damages DNA by forming interstrand cross-links that block replication and transcription, leading to cell death.
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| ln Vitro |
SG3199 exhibits strong cytotoxicity, with an average GI50 of 151.5 pM, against a range of solid tumors and blood DNA lines in humans. Cells lacking homologous recombination repair (HRR) or the DNA repair protein ERCC1 are weighted higher at SG3199, which is only multidrug-general. Cross-linking in dosage is seen in cells, and SG3199 produces DNA interstrand cross-linking mechanisms in bare linear DNA [1].
SG3199 is potently cytotoxic against a panel of human solid tumor and hematological cancer cell lines with a mean GI50 of 151.5 pM. Cells defective in DNA repair protein ERCC1 or homologous recombination repair show increased sensitivity to SG3199. The drug is only moderately susceptible to multidrug resistance mechanisms. SG3199 is highly efficient at producing DNA interstrand cross-links in naked linear plasmid DNA, and dose-dependent cross-linking is observed in cells. |
| ln Vivo |
At doses of 0.8, 5, and 50 ng/mL, the antibiotic binding of [3H]-SG3199 with adjuvant (Sprague Dawley), monkey, and human antibiotics was measured. All species have comparable rates of antibiotic binding: 97% in humans, 90% in cynomolgus monkeys, and 95% in other species [1]. After receiving intravenous infusion at 0.1 μg/kg, 0.5 μg/kg, and 1 μg/kg, SG3199 demonstrated extremely quick clearance in FX. T1/2 ranged from 8 to 42 minutes, and fast clearance was observed in the 0.5 μg/kg and 1 μg/kg dosage groups between 1000 and 1500 mL/h/kg [1].
The in vitro binding of [³H]-SG3199 to plasma proteins of rat (Sprague Dawley), cynomolgus monkey, and human at concentrations of 0.8, 5, and 50 ng/mL is determined. Plasma protein binding is high in all species: rat 89.7%, cynomolgus monkey 89.9%, and human 89.5%. Following intravenous administration at 0.1 μg/kg, 0.5 μg/kg, and 1 μg/kg, SG3199 shows very rapid clearance in rats. At 0.5 μg/kg and 1 μg/kg dose groups, clearance is between 1000 and 1500 mL/h/kg, with a T1/2 between 8 and 42 minutes. |
| Enzyme Assay |
DNA interstrand cross-linking is assessed using naked linear plasmid DNA incubated with SG3199 at various concentrations. Cross-link formation is analyzed by agarose gel electrophoresis, where cross-linked species migrate more slowly. Thermal denaturation and renaturation assays quantify cross-linking efficiency. Binding to the DNA minor groove is confirmed by circular dichroism spectroscopy or DNA footprinting. Competitive binding assays with known minor groove binders can also be performed to determine sequence selectivity.
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| Cell Assay |
In vitro cytotoxicity is evaluated using a panel of human solid tumor and hematological cancer cell lines. Cells are exposed to SG3199 at various concentrations for 72-96 hours, and cell viability is measured using MTT, XTT, or CellTiter-Glo assays. 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. Cells defective in DNA repair proteins are used to evaluate the role of repair pathways in drug sensitivity.
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| Animal Protocol |
SG3199 is typically administered intravenously in preclinical pharmacokinetic studies. In rats, doses of 0.1, 0.5, and 1 μg/kg are used to evaluate clearance and half-life. Blood samples are collected at various time points post-administration, and plasma concentrations are determined by LC-MS/MS. Pharmacokinetic parameters including clearance, volume of distribution, and half-life are calculated. Plasma protein binding is determined using equilibrium dialysis or ultrafiltration at relevant concentrations.
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| ADME/Pharmacokinetics |
SG3199 has a molecular weight of 584.66 and molecular formula C33H36N4O6. It is soluble in DMSO (130 mg/mL, 222.35 mM) with ultrasonic assistance. For in vivo use, formulations include 10% DMSO + 40% PEG300 + 5% Tween-80 + 45% saline, or 10% DMSO + 90% corn oil (≥3.25 mg/mL, clear solution). Storage is at -20°C, protected from light and under nitrogen; in solvent at -80°C for 6 months or -20°C for 1 month.
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| Toxicity/Toxicokinetics |
Plasma protein binding of SG3199 is high across species (rat 89.7%, cynomolgus monkey 89.9%, human 89.5%). Following intravenous administration in rats, the compound shows very rapid clearance (1000-1500 mL/h/kg) with a short half-life (8-42 minutes). The rapid clearance and high potency suggest that SG3199 is designed as a highly active warhead that exerts its cytotoxic effect quickly upon delivery to target cells. Toxicity is primarily related to DNA damage and is dose-dependent.
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| References |
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| Additional Infomation |
SG3199 is a pyrrolobenzodiazepine (PBD) dimer and a cytotoxic DNA minor groove interstrand crosslinking agent. It serves as the released warhead component of the ADC payload Tesirine (SG3249). SG3199 is used in the development of antibody-drug conjugates (ADCs) for targeted cancer therapy. Its extreme potency (mean GI50 151.5 pM) and mechanism of action make it a valuable tool for studying DNA crosslinking, ADC payload design, and targeted chemotherapy. The compound is for research use only and not for therapeutic use.
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| Molecular Formula |
C33H36N4O6
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|---|---|
| Molecular Weight |
584.662148475647
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| Exact Mass |
584.263
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| CAS # |
1595275-71-0
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| Related CAS # |
1595275-71-0
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| PubChem CID |
90132565
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| Appearance |
White to off-white solid powder
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| LogP |
2.8
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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 |
1080
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| Defined Atom Stereocenter Count |
2
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| SMILES |
O(CCCCCOC1C(=CC2=C(C=1)N=C[C@@H]1CC(C)=CN1C2=O)OC)C1C(=CC2=C(C=1)N=C[C@@H]1CC(C)=CN1C2=O)OC
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| InChi Key |
YMTZZJOPSATRTO-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/h12-19,22-23H,5-11H2,1-4H3/t22-,23-/m0/s1 SMILES
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| Chemical Name |
(11aS,11a'S)-8,8'-(Pentane-1,5-diylbis(oxy))bis(7-methoxy-2-methyl-1,11a-dihydro-5H-benzo[e]pyrrolo[1,2-a][1,4]diazepin-5-one)
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| Synonyms |
SG-3199 SG 3199 SG3199
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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: (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)
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| Solubility (In Vitro) |
DMSO : ~130 mg/mL (~222.35 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 3.25 mg/mL (5.56 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 32.5 mg/mL clear DMSO stock solution to 400 μL of PEG300 and mix evenly; then add 50 μL of Tween-80 to the above solution and mix evenly; then add 450 μL of 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: ≥ 3.25 mg/mL (5.56 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 32.5 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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