Glesatinib HCl (MGCD265 HCl) is an orally bioactive, potent dual MET/SMO inhibitor. Glesatinib HCl is a tyrosine kinase inhibitor (TKI) that antagonizes P-glycoprotein-mediated multidrug resistance (MDR) in non-small cell lung cancer (NSCLC).

Physicochemical Properties

Molecular Formula	C31H28CLF2N5O3S2
Molecular Weight	656.1655
Exact Mass	655.129
Elemental Analysis	C, 56.75; H, 4.30; Cl, 5.40; F, 5.79; N, 10.67; O, 7.31; S, 9.77
CAS #	1123838-51-6
Related CAS #	Glesatinib;936694-12-1
PubChem CID	127255607
Appearance	Off-white to pink solid powder
Hydrogen Bond Donor Count	4
Hydrogen Bond Acceptor Count	10
Rotatable Bond Count	11
Heavy Atom Count	44
Complexity	902
Defined Atom Stereocenter Count	0
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
InChi Key	TUVXGVPWXBWWEP-UHFFFAOYSA-N
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
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
Synonyms	Glesatinib HCl; MGCD265 hydrochloride; Glesatinib hydrochloride; MGCD265 hydrochloride; MGCD 265 HCl; MGCD265 hydrochloride; MGCD-265 HCl; MGCD265 HCl
HS Tariff Code	2934.99.9001
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)

Biological Activity

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].
ln Vivo	Glesatinib hydrochloride (MGCD265 hydrochloride; 15 mg/kg/day; orally; 40 weeks) causes the tumor's size to significantly decrease[1].
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.
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
References	[1]. Dual MET and SMO Negative Modulators Overcome Resistance to EGFR Inhibitors in Human Nonsmall Cell Lung Cancer. J Med Chem. 2017 Sep 14;60(17):7447-7458. [2]. Glesatinib, a c-MET/SMO Dual Inhibitor, Antagonizes P-glycoprotein Mediated MultidrugResistance in Cancer Cells. Front Oncol. 2019 Apr 25;9:313.

Solubility Data

Solubility (In Vitro)

DMSO: ~50 mg/mL (~76.2 mM) H2O: < 0.1 mg/mL

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. 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. 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 corn oil and mix evenly.  (Please use freshly prepared in vivo formulations for optimal results.)

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.