Art. -Nr.: HY-103702

TIP48/49-IN-1

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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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Reinheit: 99.07%
CAS. Nr.: 1807337-58-1
Formel: C₂₈H₃₀ClN₅O₄
Molecular Weight:536.02

Speicherung:

Powder -20°C, 3 years , 4°C, 2 years ; In solvent -80°C, 6 months , -20°C, 1 month

TIP48/49-IN-1 Chemical Structure

CAS. Nr.: 1807337-58-1

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Biologische Aktivität
- Beschreibung
- In Vitro
- In Vivo
Chemical Information
Lösungsmittel & Löslichkeit
- In Vitro
- In Vivo
Reinheit & Dokumentation
Verweise
Help & FAQs
Classifications
Bioz

Biologische Aktivität

Beschreibung

Alle DNA/RNA Synthesis Isoform-spezifische Produkte anzeigen :

In Vitro

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.

Western Blot Analysis^[1]

Cell Line:

H2009 non-small cell lung cancer (NSCLC) cells
Concentration:

100 nM
Incubation Time:

3 days
Result:

Depleted cellular levels of PIKK-family members DNA-PKCS (PRKDC), ATM, and ATR.

Cell Cycle Analysis^[1]

Cell Line:

Sensitive NSCLC cell lines including H2009
Concentration:

100 nM
Incubation Time:

48 h
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.

Immunofluorescence^[1]

Cell Line:

H2009 NSCLC cells and HBEC3KT normal cells
Concentration:

25 nM
Incubation Time:

3 days pre-incubation plus continuous incubation during post-IR repair period
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.

In Vivo

TIP48/49-IN-1 (Compound B) (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) significantly inhibits H₂009 NSCLC xenograft growth in female NOD.CB17-PrkdcSCID/J mice by depleting RUVBL1/2-dependent PIKK-family proteins^[1].
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.

Animal Model:

NOD.CB17-PrkdcSCID/J (female, 10-12 weeks old, average weight ~21g, subcutaneous xenograft of H2009 NSCLC cells)^[1]
Dosage:

175 mg/kg/day
Administration:

p.o.; twice daily on treatment days; schedule: 4 days on, 9 days off, 3 days on, 7 days off, 3 days on
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.

Animal Model:

NOD.CB17-PrkdcSCID/J (female, 10-12 weeks old, average weight ~21g, subcutaneous xenograft of H596 NSCLC cells)^[1]
Dosage:

175 mg/kg/day
Administration:

p.o.; twice daily on treatment days; schedule: 4 days on, 9 days off, 3 days on, 7 days off, 3 days on
Result:

Reduced tumor growth (with a smaller effect than in H2009 xenografts).
Depleted tumor levels of ATM, ATR, and DNA-PKCS proteins.

Animal Model:

Crl:NU-Foxn1nu nude (female, 10-12 weeks old, average weight ~23g, subcutaneous xenograft of H1299 NSCLC cells)^[1]
Dosage:

125 mg/kg/day
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
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

CAS. Nr. 1807337-58-1
Appearance Solid
Molecular Weight 536.02
Formel C₂₈H₃₀ClN₅O₄
Color White to off-white
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
Versand

Room temperature in continental US; may vary elsewhere.

Speicherung

Powder	-20°C	3 years
	4°C	2 years
In solvent	-80°C	6 months
	-20°C	1 month

Lösungsmittel & Löslichkeit

In Vitro:

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)

View the Complete Stock Solution Preparation Table

Preparing Stock Solutions

View the Complete Stock Solution Preparation Table

Concentration Solvent Mass

1 mg

5 mg

10 mg

Concentration

Solvent

Mass

1 mM

1.8656 mL

9.3280 mL

18.6560 mL

5 mM

0.3731 mL

1.8656 mL

3.7312 mL

10 mM

0.1866 mL

0.9328 mL

1.8656 mL

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.

Molaritätsrechner

Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)

Mass Mass

Konzentration Konzentration

Volumen Volumen

Molecular Weight Molecular Weight

Verdünnungsrechner

Konzentration _{(Stammlösung)} × Volumen _{(Stammlösung)} = Konzentration _{(Ziellösung)} × Volumen _{(Ziellösung)}

Konzentration _{(Stammlösung)} Konzentration _{(Stammlösung)}

Volumen _{(Stammlösung)} Volumen _{(Stammlösung)}

Konzentration _{(Ziellösung)} Konzentration _{(Ziellösung)}

Volumen _{(Ziellösung)} Volumen _{(Ziellösung)}

In Vivo:

Select the appropriate dissolution method based on your experimental animal and administration route.

Stock Solution Working Solution

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.

Protocol 1

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.

Protocol 2

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.

Protocol 3

Add each solvent one by one: 10% DMSO 90% Corn Oil

Solubility: ≥ 3.75 mg/mL (7.00 mM); Clear solution

This protocol yields a clear solution of ≥ 3.75 mg/mL (saturation unknown). If the continuous dosing period exceeds half a month, please choose this protocol carefully.

Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (37.5 mg/mL) to 900 μL Corn oil, and mix evenly.

In Vivo Dissolution Calculator

Please enter the basic information of animal experiments:

Dosage Dosage
mg/kg
Animal Weight (Per Animal) Animal Weight (Per Animal)
g
Dosing Volume (Per Animal) Dosing Volume (Per Animal)
μL
Number of Animals Number of Animals

Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.

Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.

Please enter your animal formula composition:

%
DMSO +

Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
%
+
+
%
Tween-80 + +
%
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

Reinheit & Dokumentation

Select Batch:

Reinheit: 99.98%

Assay: 99.98%

ee.: 99.98%

Data Sheet (282 KB)
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)
COA (2659 KB)
Elemental Analysis Report (2659 KB)
HNMR (2659 KB)
CNMR (2659 KB)
RP-HPLC (2659 KB)
NP-HPLC (2659 KB)
MS (2659 KB)
LCMS (2659 KB)
IR (2659 KB)
GC (2659 KB)
OR (2659 KB)
SDS-PAGE (2659 KB)
SEC-HPLC (2659 KB)
Other Report (2659 KB)
Handling Instructions (2659 KB)

Verweise

[1]. Yenerall P, et al. RUVBL1/RUVBL2 ATPase Activity Drives PAQosome Maturation, DNA Replication and Radioresistance in Lung Cancer. Cell Chem Biol. 2020;27(1):105-121.e14. [Content Brief]

Help & FAQs

How should lyophilized recombinant proteins be reconstituted and stored?

1. Before opening the cap, centrifuge the vial at 13000 rpm for 20-30 seconds. This step will ensure that any lyophilized powder that may have adhered to the cap or walls is collected at the bottom of the vial, minimizing the risk of product loss.

Complete Stock Solution Preparation Table

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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TIP48/49-IN-1

MCE Bioactive Compound Library

Alle DNA/RNA Synthesis Isoform-spezifische Produkte anzeigen

Biologische Aktivität

Chemical Information

Lösungsmittel & Löslichkeit

Reinheit & Dokumentation

Verweise

Help & FAQs

Complete Stock Solution Preparation Table

TIP48/49-IN-1 Related Classifications

Art. -Nr.: HY-103702