1. Protein Tyrosine Kinase/RTK
  2. ALK
    c-Met/HGFR
  3. X-376

X-376 

Cat. No.: HY-16590 Purity: 98.36%
Handling Instructions

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.

For research use only. We do not sell to patients.

X-376 Chemical Structure

X-376 Chemical Structure

CAS No. : 1365267-27-1

Size Price Stock Quantity
10 mM * 1 mL in DMSO USD 405 In-stock
Estimated Time of Arrival: December 31
2 mg USD 168 In-stock
Estimated Time of Arrival: December 31
5 mg USD 336 In-stock
Estimated Time of Arrival: December 31
10 mg USD 540 In-stock
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25 mg USD 1140 In-stock
Estimated Time of Arrival: December 31
50 mg USD 1800 In-stock
Estimated Time of Arrival: December 31
100 mg USD 2880 In-stock
Estimated Time of Arrival: December 31
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Based on 1 publication(s) in Google Scholar

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Description

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[1].

IC50 & Target[1]

ALK

0.61 nM (IC50)

MET

0.69 nM (IC50)

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].

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 Cmax of 5.04 μM[1].

Molecular Weight

547.41

Formula

C₂₅H₂₅Cl₂FN₆O₃

CAS No.

1365267-27-1

SMILES

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

Shipping

Room temperature in continental US; may vary elsewhere.

Storage
Powder -20°C 3 years
  4°C 2 years
In solvent -80°C 6 months
  -20°C 1 month
Solvent & Solubility
In Vitro: 

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

Preparing
Stock Solutions
Concentration Solvent Mass 1 mg 5 mg 10 mg
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.
In Vivo:
  • 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

  • 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

  • 3.

    Add each solvent one by one:  10% DMSO    90% corn oil

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

*All of the co-solvents are provided by MCE.
References
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].

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.

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

References
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Keywords:

X-376X376X 376ALKc-Met/HGFRAnaplastic lymphoma kinaseALK tyrosine kinase receptorCD246Cluster of differentiation 246Inhibitorinhibitorinhibit

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X-376
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HY-16590
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