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| Targets |
Glesatinib hydrochloride targets MET receptor tyrosine kinase and its oncogenic variants, including MET exon 14 skipping mutations, as well as SMO (Smoothened) and Axl receptor tyrosine kinase. It is a multi-targeted tyrosine kinase inhibitor with potential antineoplastic activity.
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| ln Vitro |
Glesatinib hydrochloride (MGCD265 hydrochloride; 0.01-5 μM; for 72 hours) inhibits the growth of cancer cells in a dose-dependent manner and exhibits a low IC50 value of 0.08 μM on NSCLC H1299 cells[1].
Glesatinib hydrochloride (0.01, 0.1, 0.5, 1 μM) dramatically increases the percentage of apoptotic cells by several times in NSCLC H1299 cells[1]. Glesatinib hydrochloride exhibits cytotoxicity against P-gp overexpressing cancer cells KB-C2, SW620/Ad300, HEK293/ABCB1, as well as their parent cells KB-3-1, SW620, and HEK293 cells, with IC50 values ranging from 5 to 10 μM[1]. Glesatinib hydrochloride (1, 3 μM; 120 mins) enhances intracellular [3H]-Inhibits and accumulates papalitaxel [3H]In cancer cell lines overexpressing P-gp, parietaxel efflux is observed[2]. Glesatinib hydrochloride (0-40 μM) increases P-gp transporters' ATPase activity in a dose-dependent way[2]. In vitro, Glesatinib hydrochloride inhibits MET and SMO kinase activity, leading to reduced tumor cell proliferation and survival. It also reverses P-gp-mediated multidrug resistance in NSCLC cells. The compound demonstrates potent activity against cancer cell lines with MET alterations. |
| ln Vivo |
Glesatinib hydrochloride (MGCD265 hydrochloride; 15 mg/kg/day; orally; 40 weeks) causes the tumor's size to significantly decrease[1].
In vivo, Glesatinib hydrochloride exhibits antitumor efficacy in preclinical models, including xenograft models of NSCLC and other MET-driven tumors. As an orally bioavailable agent, it achieves significant tumor growth inhibition. It is expected to selectively target tumors in patients with driver alterations. |
| Enzyme Assay |
In vitro enzyme binding assays for Glesatinib hydrochloride are performed using purified recombinant MET and SMO kinases. The compound is incubated with the kinases, ATP, and peptide substrates. Kinase activity is measured using luminescence-based (e.g., ADP-Glo) or fluorescence-based methods. IC50 values are determined from dose-response curves.
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| Cell Assay |
Cell Line: NSCLC H1299 cells
Concentration: 0.01, 0.1, 1, 2, 5 μM Incubation Time: For 72 hours Result: Resulted in a dose-dependent inhibition of cancer cell growth and showed the lowest IC50 value of 0.08 μM. Cellular assays for Glesatinib hydrochloride are conducted using NSCLC cell lines with MET amplification or exon 14 skipping mutations. Cells are treated with serial dilutions of the compound (0.1 nM to 10 uM) for 48-72 hours. Cell viability is assessed by MTT or CellTiter-Glo assays. MET phosphorylation and downstream signaling (AKT, ERK) are evaluated by Western blot. P-gp function is assessed by rhodamine 123 efflux assays. |
| Animal Protocol |
4−6-week old female balb/c athymic (nu/nu) mice with HCC827 NSCLC tumor xenografts
15 mg/kg Orally; daily; 40 weeks In vivo efficacy studies for Glesatinib hydrochloride are conducted in xenograft mouse models bearing MET-driven human tumors. The compound is administered orally at doses typically ranging from 10-100 mg/kg on a daily or intermittent schedule. Tumor volume is measured, and TGI is calculated. Pharmacodynamic markers including MET phosphorylation in tumor tissues are assessed by immunohistochemistry or Western blot. |
| ADME/Pharmacokinetics |
Pharmacokinetic properties of Glesatinib hydrochloride include good oral bioavailability. The compound has a molecular weight of 656.17 and formula C31H28ClF2N5O3S2. It is typically formulated for oral administration. Detailed PK parameters such as half-life, Cmax, and AUC are available in preclinical study reports.
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| Toxicity/Toxicokinetics |
Toxicological data for Glesatinib hydrochloride indicate a manageable safety profile. As a tyrosine kinase inhibitor, potential adverse effects may include gastrointestinal disturbances, fatigue, and hematological changes. Standard toxicology assessments are conducted in animal models. No significant unexpected toxicity has been reported.
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| References |
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| Additional Infomation |
Glesatinib hydrochloride (MGCD265 hydrochloride) is a research-use compound not approved for clinical therapeutic applications. It is a potent oral MET/SMO dual inhibitor with activity against MET exon 14 skipping mutations and P-gp-mediated MDR in NSCLC. The compound is used in oncology research to study MET-driven tumorigenesis and drug resistance mechanisms.
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| Molecular Formula |
C31H28CLF2N5O3S2
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| Molecular Weight |
656.1655
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| Exact Mass |
655.129
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| Elemental Analysis |
C, 56.75; H, 4.30; Cl, 5.40; F, 5.79; N, 10.67; O, 7.31; S, 9.77
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| CAS # |
1123838-51-6
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| Related CAS # |
Glesatinib;936694-12-1
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| PubChem CID |
127255607
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| Appearance |
Off-white to pink solid powder
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| Hydrogen Bond Donor Count |
4
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| Hydrogen Bond Acceptor Count |
10
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| Rotatable Bond Count |
11
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| Heavy Atom Count |
44
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| Complexity |
902
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| Defined Atom Stereocenter Count |
0
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| SMILES |
Cl[H].S1C2=C(C([H])=C([H])N=C2C([H])=C1C1C([H])=C([H])C(=C([H])N=1)C([H])([H])N([H])C([H])([H])C([H])([H])OC([H])([H])[H])OC1C([H])=C([H])C(=C([H])C=1F)N([H])C(N([H])C(C([H])([H])C1C([H])=C([H])C(=C([H])C=1[H])F)=O)=S
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| InChi Key |
TUVXGVPWXBWWEP-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C31H27F2N5O3S2.ClH/c1-40-13-12-34-17-20-4-8-24(36-18-20)28-16-25-30(43-28)27(10-11-35-25)41-26-9-7-22(15-23(26)33)37-31(42)38-29(39)14-19-2-5-21(32)6-3-19;/h2-11,15-16,18,34H,12-14,17H2,1H3,(H2,37,38,39,42);1H
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| Chemical Name |
N-[[3-fluoro-4-[2-[5-[(2-methoxyethylamino)methyl]pyridin-2-yl]thieno[3,2-b]pyridin-7-yl]oxyphenyl]carbamothioyl]-2-(4-fluorophenyl)acetamide;hydrochloride
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| Synonyms |
Glesatinib HCl; MGCD265 hydrochloride; Glesatinib hydrochloride; MGCD265 hydrochloride; MGCD 265 HCl; MGCD265 hydrochloride; MGCD-265 HCl; MGCD265 HCl
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO: ~50 mg/mL (~76.2 mM)
H2O: < 0.1 mg/mL |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (3.81 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (3.81 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (3.81 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.5240 mL | 7.6200 mL | 15.2400 mL | |
| 5 mM | 0.3048 mL | 1.5240 mL | 3.0480 mL | |
| 10 mM | 0.1524 mL | 0.7620 mL | 1.5240 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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