Theliatinib (HMPL-309)

Catalog No.S8584 Batch:S858401

Technical Data

Formula

C₂₅H₂₆N₆O₂

Molecular Weight

442.51

CAS No.

1353644-70-8

Solubility (25°C)*

In vitro

DMSO

47 mg/mL (106.21 mM)

In Vivo (Add solvents to the product individually and in order.)

Homogeneous suspension

CMC-NA

≥5mg/ml

Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.

* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.
* Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

Preparing Stock Solutions

Biological Activity

Description

Theliatinib (HMPL-309) is a highly potent EGFR inhibitor with Ki value of 0.05 nM against the wild type EGFR and IC50 values of 3 nM and 22 nM against EGFR and EGFR T790M/L858R mutant. It demonstrates 50 fold greater selectivity for EGFR compared to 72 other kinases.

Targets

WT EGFR (Cell-free assay)	EGFR T790M/L858R (Cell-free assay)
3 nM	22 nM

In vitro

In comparison to erlotinib or gefitinib, theliatinib (HMPL-309) shows much stronger binding affinity to wild type EGFR and is more difficult to be replaced by ATP. This unique feature may result in better target engagement for this compound compared to erlotinib or gefitinib, leading to stronger anti-tumour activity in tumours with wild type EGFR activation due to gene amplification or protein overexpression. It inhibits EGFR phosphorylation with an IC50 of 0.007 μM for EGF stimulated EGFR phosphorylation in A431 cells and cell survival in tumour cells with wild-type EGFR (A431, H292, FaDu cells).

In Vivo

Theliatinib (HMPL-309) demonstrates dose-dependent anti-tumour activity in a panel of PDECX (patient-derived oesophageal cancer xenograft) models with a generally good correlation between EGFR H score and tumour growth inhibition. Furthermore, aberrant activation or gene mutations of other targets such as PI3K and FGFR diminish the anti-tumour activity of EGFR TKIs, especially this compound.

Protocol (from reference)

Cell Assay:^{^[1]}	Cell Lines A431 cells Concentrations 0.005-10 μM Incubation Time 48 h Method A431 cells (1 × 10⁴ cells/well) in exponential phase are seeded in duplicates in DMEM containing 10% FBS and incubated at 37°C and 5% CO2 overnight. Then, 10 μL of test compounds (including theliatinib (HMPL-309), gefitinib and erlotinib) at tested concentrations (10~0.005 μM, 3 fold gradient dilution) are added into each well with the final concentration of DMSO at 0.5%. The cells are incubated for 48 h followed by further incubation for 1h after adding 10 μL/well CCK-8 solution. Cell survival is determined by measuring the optical density at 450 nm.
Animal Study:^{^[1]}	Animal Models Seven to nine week old NOD-SCID immunodeficient or BALB/cASlac-nu/nu male or female mice (Tumor-bearing mice) Dosages 15 mg/kg/day Administration oral

Cell Assay:^{^[1]}

Cell Lines
A431 cells
Concentrations
0.005-10 μM
Incubation Time
48 h
Method
A431 cells (1 × 10⁴ cells/well) in exponential phase are seeded in duplicates in DMEM containing 10% FBS and incubated at 37°C and 5% CO2 overnight. Then, 10 μL of test compounds (including theliatinib (HMPL-309), gefitinib and erlotinib) at tested concentrations (10~0.005 μM, 3 fold gradient dilution) are added into each well with the final concentration of DMSO at 0.5%. The cells are incubated for 48 h followed by further incubation for 1h after adding 10 μL/well CCK-8 solution. Cell survival is determined by measuring the optical density at 450 nm.

Animal Study:^{^[1]}

Animal Models
Seven to nine week old NOD-SCID immunodeficient or BALB/cASlac-nu/nu male or female mice (Tumor-bearing mice)
Dosages
15 mg/kg/day
Administration
oral

References

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5584209/

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SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

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