TIP48/49-IN-1
Based on 1 Customer Validation
TIP48/49-IN-1 is an orally active, specific RUVBL1/2 (TIP48/49) ATPase inhibitor with an IC50 of 59 nM against purified RUVBL1/2. TIP48/49-IN-1 inhibits the DNA replication process, leading to S-phase arrest. TIP48/49-IN-1 induces apoptosis. TIP48/49-IN-1 can be used for the research of non-small cell lung cancer (NSCLC) cells.
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- Pureté: 99.07%
- CAS No.: 1807337-58-1
- Formule: C28H30ClN5O4
- Masse moléculaire:536.02
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Stockage:Powder -20°C, 3 years , 4°C, 2 years ; In solvent -80°C, 6 months , -20°C, 1 month
To place orders, for customer services and technical support, please contact: MedChemExpress USA
Tel: 609-228-6898 E-mail: [email protected] [email protected]
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Activité biologique
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Chemical Information
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Solvant et solubilité
- Pureté et documentation
- Références
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Help & FAQs
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Activité biologique
TIP48/49-IN-1 (Compound B) (100 nM; 3 days) depletes the PIKK family proteins ATM, ATR and DNA-PKCS in H2009 NSCLC cells[1].
TIP48/49-IN-1 (100 nM; 24 h) alters the transcriptome of H2009 and H596 non-small cell lung cancer (NSCLC) cells, and significantly downregulates DNA replication-related genes[1].
TIP48/49-IN-1 (100 nM; 12 h) enhances the binding of PAQosome components to RUVBL1 and impairs PAQosome maturation/dissociation in H2009 non-small cell lung cancer cells[1].
TIP48/49-IN-1 (100 nM; 48 h) induces S-phase arrest and subsequent apoptosis in sensitive non-small cell lung cancer (NSCLC) cell lines, including H2009[1].
TIP48/49-IN-1 (100 nM; 24 h) delays S-phase progression in synchronized H2009 non-small cell lung cancer cells[1].
TIP48/49-IN-1 (100 nM; 12-72 h) initially reduces the levels of ssDNA and chromatin-bound RPA2 in H2009 non-small cell lung cancer cells, and subsequently induces replication catastrophe at 48 h, accompanied by high levels of ssDNA and RPA hyperloading[1].
TIP48/49-IN-1 (100 nM; 6-12 h) accelerates the replication fork speed of H2009 non-small cell lung cancer (NSCLC) cells at 6 h post-treatment[1].
TIP48/49-IN-1 (100 nM; 12 h) increases POLE abundance at active replication forks in H2009 non-small cell lung cancer cells and reduces core histone abundance[1].
TIP48/49-IN-1 (25-50 nM; 3 days) radiosensitizes 8 NSCLC cell lines, but exerts no such effect on normal bronchial epithelial cells HBEC3KT or HBEC30KT[1].
TIP48/49-IN-1 (25 nM; 3 days) slows the DSB repair kinetics in H2009 non-small cell lung cancer cells, but exerts no such effect on HBEC3KT normal bronchial epithelial cells[1].
TIP48/49-IN-1 (150 nM; 3 days) inhibits ionizing radiation damage repair in organoids derived from 5 patients with primary non-small cell lung cancer[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:H2009 non-small cell lung cancer (NSCLC) cells
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Concentration:100 nM
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Incubation Time:3 days
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Result:Depleted cellular levels of PIKK-family members DNA-PKCS (PRKDC), ATM, and ATR.
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Cell Line:Sensitive NSCLC cell lines including H2009
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Concentration:100 nM
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Incubation Time:48 h
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Result:Induced S-phase arrest, followed by progression to apoptosis evidenced by a sub-G1 population.
Increased γH2AX (a marker of replication stress) and cleaved PARP1 (a marker of apoptosis) in H2009 cells as confirmed by immunoblotting.
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Cell Line:H2009 NSCLC cells and HBEC3KT normal cells
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Concentration:25 nM
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Incubation Time:3 days pre-incubation plus continuous incubation during post-IR repair period
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Result:Delayed the resolution of γH2AX and 53BP1 foci post-IR in H2009 cells, indicating impaired DSB repair.
Had no effect on DSB repair kinetics in HBEC3KT cells.
TIP48/49-IN-1 (175 mg/kg/day; p.o.; twice daily on treatment days; schedule: 4 days on, 9 days off, 3 days on, 7 days off, 3 days on) inhibits H596 NSCLC xenograft growth in female NOD.CB17-PrkdcSCID/J mice by depleting RUVBL1/2-dependent PIKK-family proteins, with modest efficacy relative to H2009 tumors[1].
TIP48/49-IN-1 (125 mg/kg/day; p.o.; twice daily on treatment days; schedule: 4 days of treatment with 9 A.M. and 5 P.M. doses, plus 2 Gy IR at 12 P.M. on treatment days, with an additional 2 Gy IR on the fifth day) potentiates the antitumor efficacy of ionizing radiation in H1299 NSCLC xenografts without causing obvious toxicity in female nude mice[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:NOD.CB17-PrkdcSCID/J (female, 10-12 weeks old, average weight ~21g, subcutaneous xenograft of H2009 NSCLC cells)[1]
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Dosage:175 mg/kg/day
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Administration:p.o.; twice daily on treatment days; schedule: 4 days on, 9 days off, 3 days on, 7 days off, 3 days on
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Result:Reduced tumor growth.
Depleted tumor levels of ATM, ATR, and DNA-PKCS proteins.
Decreased ATM-positive tumor cell nuclei.
Induced stressed and vacuolated nuclei in tumors by H&E staining.
Caused transient bodyweight loss with no marked changes in kidney, liver, spleen, or small intestine tissue architecture or morphology.
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Animal Model:NOD.CB17-PrkdcSCID/J (female, 10-12 weeks old, average weight ~21g, subcutaneous xenograft of H596 NSCLC cells)[1]
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Dosage:175 mg/kg/day
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Administration:p.o.; twice daily on treatment days; schedule: 4 days on, 9 days off, 3 days on, 7 days off, 3 days on
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Result:Reduced tumor growth (with a smaller effect than in H2009 xenografts).
Depleted tumor levels of ATM, ATR, and DNA-PKCS proteins.
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Animal Model:Crl:NU-Foxn1nu nude (female, 10-12 weeks old, average weight ~23g, subcutaneous xenograft of H1299 NSCLC cells)[1]
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Dosage:125 mg/kg/day
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Administration:p.o.; twice daily on treatment days; schedule: 4 days of treatment with 9 A.M. and 5 P.M. doses, plus 2 Gy IR at 12 P.M. on treatment days, with an additional 2 Gy IR on the fifth day
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Result:Showed no effect on tumor growth when administered alone.
Significantly potentiated IR-induced tumor growth inhibition when combined with ionizing radiation.
Caused no obvious toxicity, as measured by stable mouse bodyweight.
Reduced ATM protein levels in tumors.
Chemical Information
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CAS No. 1807337-58-1
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Appearance Solid
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Masse moléculaire 536.02
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Formule C28H30ClN5O4
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Color White to off-white
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SMILES
CCOC(C=CC(Cl)=C1)=C1C2=NN=C([C@@H](CCC3)C[C@@H]3C(NC(C(N(C4=CC=CC=C4)N5C)=O)=C5C)=O)O2
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Livraison
Room temperature in continental US; may vary elsewhere.
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Stockage
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Solvant et solubilité
DMSO : 100 mg/mL (186.56 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: ≥ 3.75 mg/mL (7.00 mM); Clear solution
This protocol yields a clear solution of ≥ 3.75 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (37.5 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.
Add each solvent one by one: 10% DMSO 90% (20% SBE-β-CD in Saline)
Solubility: ≥ 3.75 mg/mL (7.00 mM); Clear solution
This protocol yields a clear solution of ≥ 3.75 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (37.5 mg/mL) to 900 μL 20% SBE-β-CD in Saline, and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C, storage for one week): 2 g SBE-β-CD powder is dissolved in 10 mL Saline, completely dissolve until clear.
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.
Pureté et documentation
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Fiche technique (282 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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Instruction de manipulation (2659 KB)
Références
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 | 1.8656 mL | 9.3280 mL | 18.6560 mL | 46.6400 mL |
| 5 mM | 0.3731 mL | 1.8656 mL | 3.7312 mL | 9.3280 mL | |
| 10 mM | 0.1866 mL | 0.9328 mL | 1.8656 mL | 4.6640 mL | |
| 15 mM | 0.1244 mL | 0.6219 mL | 1.2437 mL | 3.1093 mL | |
| 20 mM | 0.0933 mL | 0.4664 mL | 0.9328 mL | 2.3320 mL | |
| 25 mM | 0.0746 mL | 0.3731 mL | 0.7462 mL | 1.8656 mL | |
| 30 mM | 0.0622 mL | 0.3109 mL | 0.6219 mL | 1.5547 mL | |
| 40 mM | 0.0466 mL | 0.2332 mL | 0.4664 mL | 1.1660 mL | |
| 50 mM | 0.0373 mL | 0.1866 mL | 0.3731 mL | 0.9328 mL | |
| 60 mM | 0.0311 mL | 0.1555 mL | 0.3109 mL | 0.7773 mL | |
| 80 mM | 0.0233 mL | 0.1166 mL | 0.2332 mL | 0.5830 mL | |
| 100 mM | 0.0187 mL | 0.0933 mL | 0.1866 mL | 0.4664 mL |
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