SY-589
Based on 1 Customer Validation
SY-589 is an orally active DNA polymerase Polθ helicase domain inhibitor (IC50=2.29 nM) and DNA damage inducer. SY-589 inhibits the ATPase activity of the Polθ helicase domain and blocks the Polθ-mediated microhomology-mediated end joining (MMEJ) DNA repair pathway (IC50=0.85 nM). SY-589 also induces the accumulation of DNA double-strand breaks by increasing γ-H2AX levels. SY-589 exerts antiproliferative effects on BRCA2-deficient cells and is used in the research of HR-deficient tumors.
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- Purity: 98.50%
- CAS No.: 3077714-09-8
- 화학식: C24H18ClFN8O3S
- 분자량:552.97
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보관:Powder -20°C, 3 years , 4°C, 2 years ; In solvent -80°C, 6 months , -20°C, 1 month
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Tel: 609-228-6898 E-mail: [email protected] [email protected]
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Biological Activity
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Chemical Information
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용액&용해도
- 순도&문서
- References
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Help & FAQs
All DNA/RNA Synthesis Isoforms
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Biological Activity
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DNA Polymerase |
Helicase |
SY-589 (administered on days 0, 3, and 6) potently inhibits the viability of homologous recombination-deficient DLD1 BRCA2-/- colon cancer cells, with an IC50 of 2.71 nM[1].
SY-589 (0.05-12.8 nM; 10 d) induces dose-dependent accumulation of DNA double-strand breaks (detected by γ-H2AX levels) in DLD1 BRCA2-/- cells, and exerts dose-dependent effects on inhibiting colony formation, inducing cell cycle arrest and triggering apoptosis in DLD1 BRCA2-/- cells[1].
SY-589 (0.39-100 nM; 10 d) exerts strong synergistic effects with the PARP inhibitor Olaparib (HY-10162) to inhibit the viability of DLD1 BRCA2-/- cells, and significantly enhances the antiproliferative activity of Olaparib[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:DLD1 BRCA2-/- cells
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Concentration:0.05, 0.2, 0.8, 3.2, 12.8 nM
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Incubation Time:10 days
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Result:Induced a dose-dependent increase in γ-H2AX protein levels (a biomarker of DNA double-strand breaks), with the highest fold change observed at 12.8 nM.
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Cell Line:DLD1 BRCA2-/- cells
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Concentration:0.05, 0.8, 12.8 nM
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Incubation Time:10 days (medium refreshed every 2 days)
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Result:Induced dose-dependent changes in cell cycle distribution, increasing the S-phase population from 18.12% (control) to 28.33% at 12.8 nM.
Induced apoptosis in a dose-dependent manner, with the apoptotic rate increasing from 9.13% (control) to 34.2% at 12.8 nM.
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Cell Line:DLD1 BRCA2-/- cells
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Concentration:0.05, 0.2, 0.8, 3.2, 12.8 nM
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Incubation Time:12 days (medium refreshed every 2 days)
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Result:Suppressed colony formation in a dose-dependent manner, with complete suppression observed at 12.8 nM.
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Cell Line:DLD1 BRCA2-/- cells
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Concentration:0.39, 1.56, 6.25, 25, 100 nM (SY-589); serially diluted (Olaparib)
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Incubation Time:10 days (dosed on day 0, day 3, day 6)
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Result:Exhibited strong synergistic antiproliferative activity with Olaparib, with a Loewe synergy score of >20.
Enhanced the antiproliferative effect of Olaparib, shifting from no suppression to >50% suppression of cell proliferation when paired with low-dose Olaparib (0.15 nM).
| Species | Dose | Route | T1/2 | Tmax | Cmax | AUC0-t | AUC0-∞ | MRT0-t | MRT0-∞ | Vss | CL | F |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Mice[1] | 2 mg/kg | i.v. | 1.38 h | 0.08 h | 6661.55 ng/mL | 11178.99 ng·h/mL | 11454.79 ng·h/mL | 1.51 h | 1.70 h | 0.30 L/kg | 2.95 mL/min/kg | / |
| Mice[1] | 30 mg/kg | p.o. | 2.51 h | 0.58 h | 44547.59 ng/mL | 185078.88 ng·h/mL | 185274.47 ng·h/mL | 4.00 h | 4.02 h | / | / | 107.83 % |
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:BALB/c nude mice with Colorectal cancer (female, 6-8 weeks old)[1]
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Dosage:30 mg/kg (monotherapy TGI); 0.5 mg/kg (combination 99% TGI); 2.5 mg/kg (combination 107% TGI); 12.5 mg/kg (combination 109% TGI)
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Administration:p.o.; daily; 27 days
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Result:Achieved 59% tumor growth inhibition (TGI) as monotherapy.
Achieved 99% TGI in combination with 25 mg/kg Olaparib.
Achieved 107% TGI with marked tumor regression in combination with 25 mg/kg Olaparib.
Achieved 109% TGI with marked tumor regression in combination with 25 mg/kg Olaparib.
Caused no significant body weight changes in any treatment group during the study.
Chemical Information
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CAS No. 3077714-09-8
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Appearance Solid
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분자량 552.97
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화학식 C24H18ClFN8O3S
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Color White to off-white
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SMILES
COC1=C(C=C(Cl)N=C1)C2=CC(N3C(C(F)=CC=C3)=O)=NC=C2C(NC4=NC(C5=C(C=NN5C)C)=NS4)=O
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선적
Room temperature in continental US; may vary elsewhere.
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보관
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
용액&용해도
DMSO : 100 mg/mL (180.84 mM; ultrasonic and warming and heat to 60°C; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
Select the appropriate dissolution method based on your experimental animal and administration route.
- For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
- To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for In Vivo experiments, it is recommended to prepare freshly and use it on the same day.
- The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.
Add each solvent one by one: 10% DMSO 40% PEG300 5% Tween-80 45% Saline
Solubility: ≥ 2.5 mg/mL (4.52 mM); Suspended solution
This protocol yields a suspended solution of ≥ 2.5 mg/mL (saturation unknown). Suspended solution can be used for oral and intraperitoneal injection.
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.
Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
Please enter the basic information of animal experiments:
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Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Please enter your animal formula composition:
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%DMSO +
Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
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%+
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+%Tween-80 + +
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%Saline +
The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).
Working solution concentration: 0.22 mg/mL
Method for preparing stock solution: mg drug dissolved in μL DMSO. Stock solution concentration: mg/mL.
1. Take μL DMSO stock solution;
2. Add μL .
μL , mix evenly;
3. Then add μL Tween 80, mix evenly;
4. Then add μL
Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.
순도&문서
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Data Sheet (281 KB)
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SDS (252 KB)
- English - EN (252 KB)
- Français - FR (252 KB)
- Deutsch - DE (252 KB)
- Norwegian - NO (252 KB)
- Español - ES (252 KB)
- Swedish - SV (252 KB)
- Italian - IT (252 KB)
- Korean - KR (252 KB)
- Portuguese - PT (252 KB)
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Handling Instructions (2659 KB)
References
Complete Stock Solution Preparation Table
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
| Optional Solvent | Concentration Solvent Mass | 1 mg | 5 mg | 10 mg | 25 mg |
|---|---|---|---|---|---|
| DMSO | 1 mM | 1.8084 mL | 9.0421 mL | 18.0842 mL | 45.2104 mL |
| 5 mM | 0.3617 mL | 1.8084 mL | 3.6168 mL | 9.0421 mL | |
| 10 mM | 0.1808 mL | 0.9042 mL | 1.8084 mL | 4.5210 mL | |
| 15 mM | 0.1206 mL | 0.6028 mL | 1.2056 mL | 3.0140 mL | |
| 20 mM | 0.0904 mL | 0.4521 mL | 0.9042 mL | 2.2605 mL | |
| 25 mM | 0.0723 mL | 0.3617 mL | 0.7234 mL | 1.8084 mL | |
| 30 mM | 0.0603 mL | 0.3014 mL | 0.6028 mL | 1.5070 mL | |
| 40 mM | 0.0452 mL | 0.2261 mL | 0.4521 mL | 1.1303 mL | |
| 50 mM | 0.0362 mL | 0.1808 mL | 0.3617 mL | 0.9042 mL | |
| 60 mM | 0.0301 mL | 0.1507 mL | 0.3014 mL | 0.7535 mL | |
| 80 mM | 0.0226 mL | 0.1130 mL | 0.2261 mL | 0.5651 mL | |
| 100 mM | 0.0181 mL | 0.0904 mL | 0.1808 mL | 0.4521 mL |
SY-589 Related Classifications
HY-181557 Related Classifications
Powered by Bioz
- SY-589
- 3077714-09-8
- SY589
- SY 589
- DNA Alkylator/Crosslinker
- DNA/RNA Synthesis
- Apoptosis
- ATPase activity
- human Polθ helicase domain
- micro-homology-mediated end joining
- HR-deficient tumors
- DLD1 BRCA2-/- colon cancer cells
- homologous recombination-deficient cells
- DNA polymerase theta helicase domain
- BRCA2-deficient cells
- γ-H2AX
- DNA double-strand breaks
- Inhibitor
- inhibitor
- inhibit