Art. -Nr.: HY-16590

X-376

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X-376 is a potent and highly specific ALK tyrosine kinase inhibitor (TKI) (IC₅₀=0.61 nM). X-376 is a less potent inhibitor of MET (IC₅₀=0.69 nM). X-376 displays potent anti-tumor activity.

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Reinheit: 98.10%
CAS. Nr.: 1365267-27-1
Formel: C₂₅H₂₅Cl₂FN₆O₃
Molecular Weight:547.41

Speicherung:

Powder -20°C, 3 years , 4°C, 2 years ; In solvent -80°C, 2 years , -20°C, 1 year

X-376 Chemical Structure

CAS. Nr.: 1365267-27-1

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Fluorescent Dye

Strong Fluorescence Signal / Multi-Disciplinary Applications / High Fluorescence Specificity

Biologische Aktivität
- Beschreibung
- IC₅₀ & Target
- Cellular Effect
- In Vitro
- In Vivo
Chemical Information
Publications (1)
Lösungsmittel & Löslichkeit
- In Vitro
- In Vivo
Protokoll
Reinheit & Dokumentation
Verweise
Help & FAQs
Classifications
Bioz

Biologische Aktivität

Beschreibung

IC₅₀ & Target^[1]

ALK

0.61 nM (IC₅₀)

Cellular Effect

Cell Line	Type	Value	Description	References
MKN-45	IC₅₀	0.15 μM Compound: 18	Antiproliferative activity against human MKN-45 cells assessed as inhibition of cell growth measured after 72 hrs by Cell Titer blue assay Antiproliferative activity against human MKN-45 cells assessed as inhibition of cell growth measured after 72 hrs by Cell Titer blue assay	[PMID: 37262349]
MKN-45	IC₅₀	150 nM Compound: 27	Antiproliferative activity against human MKN-45 cells assessed as inhibition of cell growth by MTT assay Antiproliferative activity against human MKN-45 cells assessed as inhibition of cell growth by MTT assay	[PMID: 38733884]
NCI-H3122	IC₅₀	77 nM Compound: 27	Antiproliferative activity against human NCI-H3122 cells assessed as reduction in cell viability incubated for 48 hrs by MTT assay Antiproliferative activity against human NCI-H3122 cells assessed as reduction in cell viability incubated for 48 hrs by MTT assay	[PMID: 38733884]

In Vitro

The ability of X-376 to inhibit the growth of different cancer cell lines harboring ALK fusions or point mutations is tested. X-376 is potent in H3122 lung cancer cells harboring EML4-ALK E13;A20 (IC₅₀: 77 nM). X-376 is also potent in H2228 lung cancer cells harboring EML4-ALK E6a/b; A20 (IC₅₀: 57 nM). Furthermore, X-376 is potent in SUDHL-1 lymphoma cells harboring NPM-ALK (IC₅₀: 32 nM). X-376 also inhibits SY5Y neuroblastoma cells harboring ALK F1174L, MKN-45 gastric carcinoma cells harboring MET dependent, HepG2 cells and PC-9 lung cancer cell lines harboring EGFR exon 19 del with IC₅₀s of 142 nM, 150 nM, 15.137 μM and 3.062 μM, respectively^[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

In Vivo

The effects of X-376 in vivo against H3122 xenografts are examined. A pharmacokinetic study reveals that X-376 shows substantial bioavailability and moderate half-lives in vivo. Nude mice harboring H3122 xenografts are treated with X-376 at 50 mg/kg bid. X-376 significantly delays the growth of tumors compared to vehicle alone. In the xenograft experiments, X-376 appears well-tolerated in vivo. Mouse weight is unaffected by X-376 treatment. Drug-treated mice appear healthy and do not display any signs of compound related toxicity. To further assess potential side effects of X-376, additional systemic toxicity and toxico-kinetic studies are performed in Sprague Dawley (SD) rats. Following 10 days of repeated oral administration of X-376 at 25, 50, 100 mg/kg in SD rats, all animals survive to study termination. The no significant toxicity (NST) levels are determined to be 50 mg/kg for X-376. At NST levels, X-376 achieves an AUC of 41 μM×hr and a C_max of 5.04 μM^[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Chemical Information

CAS. Nr. 1365267-27-1
Appearance Solid
Molecular Weight 547.41
Formel C₂₅H₂₅Cl₂FN₆O₃
Color White to off-white
SMILES

O=C(C1=NN=C(N)C(O[C@@H](C2=C(Cl)C=CC(F)=C2Cl)C)=C1)NC3=CC=C(C(N4CCN(C)CC4)=O)C=C3
Versand

Room temperature in continental US; may vary elsewhere.

Speicherung

Powder	-20°C	3 years
	4°C	2 years
In solvent	-80°C	2 years
	-20°C	1 year

Publications (1)

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RSC Adv

Phase I metabolic profiling and unexpected reactive metabolites in human liver microsome incubations of X-376 using LC-MS/MS: bioactivation pathway elucidation and in silico toxicity studies of its metabolites. [Abstract]

2020 Feb 3;10(9):5412-5427. PMID: 35498318

Lösungsmittel & Löslichkeit

In Vitro:

DMSO : 100 mg/mL (182.68 mM; Need ultrasonic; 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

1.8268 mL

9.1339 mL

18.2678 mL

5 mM

0.3654 mL

1.8268 mL

3.6536 mL

10 mM

0.1827 mL

0.9134 mL

1.8268 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, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.

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: ≥ 2.5 mg/mL (4.57 mM); Clear solution

This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).

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.

Protocol 2

Add each solvent one by one: 10% DMSO 90% (20% SBE-β-CD in Saline)

Solubility: ≥ 2.5 mg/mL (4.57 mM); Clear solution

This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).

Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 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: ≥ 2.5 mg/mL (4.57 mM); Clear solution

This protocol yields a clear solution of ≥ 2.5 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 (25.0 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

Protokoll

Cell Assay^[1]

For viability experiments, cells are seeded in 96-well plates at 25%-33% confluency and exposed to drugs. The human lung adenocarcinoma cell lines H3122 and H2228 are treated with X-376 (10, 30, 100, 300 and 1000 nM). SUDHL-1 lymphoma cells are treated with X-376 (5, 10, 30, 100 and 300 nM). SY5Y neuroblastoma cells are treated with X-376 (30, 100, 300 and 1000 nM). At 72 hours post X-376 addition, Cell Titer Blue Reagent is added and fluorescence is measured on a Spectramax spectrophotometer. All experimental points are set up in hextuplicate replicates and are performed at least two independent times. IC₅₀s are calculated using GraphPad Prism version 5 for Windows. The curves are fit using a nonlinear regression model with a log (inhibitor) vs. response formula^[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Administration^[1]

Mice^[1]
Nude mice (nu/nu) are injected with H3122 cells. Once tumors reach an average volume of 450 mm³, a total of 27 athymic mice harboring H3122 tumors are randomized and dosed via oral gavage with 50 mg/kg X-376 or the control vehicle. Two, five, and fifteen hours after the single treatment (3 tumors/timepoint/group), mice are sacrificed and serum is collected for assessment of drug concentration using an LC-MS based bioanalytical method.

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Reinheit & Dokumentation

Select Batch:

Reinheit: 99.98%

Assay: 99.98%

ee.: 99.98%

Data Sheet (286 KB)
SDS (392 KB)
- English - EN (392 KB)
- Français - FR (392 KB)
- Deutsch - DE (392 KB)
- Norwegian - NO (392 KB)
- Español - ES (392 KB)
- Swedish - SV (392 KB)
- Italian - IT (392 KB)
- Korean - KR (392 KB)
- Portuguese - PT (392 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]. Lovly CM, et al. Insights into ALK-driven cancers revealed through development of novel ALK tyrosine kinaseinhibitors. Cancer Res. 2011 Jul 15;71(14):4920-31. [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, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.

Optional Solvent	Concentration Solvent Mass	1 mg	5 mg	10 mg	25 mg
DMSO	1 mM	1.8268 mL	9.1339 mL	18.2678 mL	45.6696 mL
	5 mM	0.3654 mL	1.8268 mL	3.6536 mL	9.1339 mL
	10 mM	0.1827 mL	0.9134 mL	1.8268 mL	4.5670 mL
	15 mM	0.1218 mL	0.6089 mL	1.2179 mL	3.0446 mL
	20 mM	0.0913 mL	0.4567 mL	0.9134 mL	2.2835 mL
	25 mM	0.0731 mL	0.3654 mL	0.7307 mL	1.8268 mL
	30 mM	0.0609 mL	0.3045 mL	0.6089 mL	1.5223 mL
	40 mM	0.0457 mL	0.2283 mL	0.4567 mL	1.1417 mL
	50 mM	0.0365 mL	0.1827 mL	0.3654 mL	0.9134 mL
	60 mM	0.0304 mL	0.1522 mL	0.3045 mL	0.7612 mL
	80 mM	0.0228 mL	0.1142 mL	0.2283 mL	0.5709 mL
	100 mM	0.0183 mL	0.0913 mL	0.1827 mL	0.4567 mL

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X-376

Kinase Inhibitor Library

Protein Tyrosine Kinase Compound Library

Anti-Cancer Compound Library

Clinical Compound Library

Drug Repurposing Compound Library

Anti-Lung Cancer Compound Library

Anti-Blood Cancer Compound Library

Angiogenesis-Related Compound Library

Anti-Liver Cancer Compound Library

Anti-Colorectal Cancer Compound Library

Cancer Stem Cells Compound Library

Membrane Protein-targeted Compound Library

Membrane Receptor-targeted Compound Library

Highly Selective Inhibitors Library

Cytokine Inhibitors Library

Serine/Threonine Kinase Inhibitor Library

Anti-Hematopathy Compound Library

Anti-Ovarian Cancer Compound Library

Multi-Target Compound Library

Bioactive Compound Library Max

MCE Bioactive Compound Library

Drug Repurposing Compound Library Plus

Clinical Compound Library Plus

Bioactive Compound Library

Anti-Gastric Cancer Compound Library

Anti-Brain Cancer Compound Library

Protein Kinase Compound Library

High-Throughput Bioactive Compound Library

Posttranslational Modification Library

Publications Citing Use of MedChemExpress (MCE) X-376

Biologische Aktivität

Chemical Information

Publications (1)

Lösungsmittel & Löslichkeit

Protokoll

Reinheit & Dokumentation

Verweise

Help & FAQs

Complete Stock Solution Preparation Table

X-376

Kinase Inhibitor Library

Protein Tyrosine Kinase Compound Library

Anti-Cancer Compound Library

Clinical Compound Library

Drug Repurposing Compound Library

Anti-Lung Cancer Compound Library

Anti-Blood Cancer Compound Library

Angiogenesis-Related Compound Library

Anti-Liver Cancer Compound Library

Anti-Colorectal Cancer Compound Library

Cancer Stem Cells Compound Library

Membrane Protein-targeted Compound Library

Membrane Receptor-targeted Compound Library

Highly Selective Inhibitors Library

Cytokine Inhibitors Library

Serine/Threonine Kinase Inhibitor Library

Anti-Hematopathy Compound Library

Anti-Ovarian Cancer Compound Library

Multi-Target Compound Library

Bioactive Compound Library Max

MCE Bioactive Compound Library

Drug Repurposing Compound Library Plus

Clinical Compound Library Plus

Bioactive Compound Library

Anti-Gastric Cancer Compound Library

Anti-Brain Cancer Compound Library

Protein Kinase Compound Library

High-Throughput Bioactive Compound Library

Posttranslational Modification Library

Publications Citing Use of MedChemExpress (MCE) X-376

Biologische Aktivität

Chemical Information

Publications (1)

Lösungsmittel & Löslichkeit

Protokoll

Reinheit & Dokumentation

Verweise

Help & FAQs

Complete Stock Solution Preparation Table

X-376 Related Classifications

HY-16590 Related Classifications