Theliatinib (HMPL-309)

Catalog No.S8584 Batch:S858401

Print

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)
 
 
* <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 demonstrats 50 fold greater selectivity for EGFR compared to 72 other kinases.
Targets
WT EGFR [1]
(Cell-free assay)		 EGFR T790M/L858R [1]
(Cell-free assay)
3 nM 22 nM
In vitro

In comparison to erlotinib or gefitnib, theliatinib 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 theliatinib compared to erlotinib or gefitinib, leading to stronger anti-tumor activity in tumors with wild type EGFR activation due to gene amplification or protein overexpression. Theliatinib inhibits EGFR phosphorylation with an IC50 of 0.007 μM for EGF stimulated EGFR phosphorylation in A431 cells and cell survival in tumor cells with wild-type EGFR (A431, H292, FaDu cells)[1].
In vivo

Theliatinib demonstrates dose-dependent anti-tumor activity in a panel of PDECX (patient-derived esophageal cancer xenograft) models with a generally good correlation between EGFR H score and tumor growth inhibition. Furthermore, aberrant activation or gene mutations of other targets such as PI3K and FGFR diminishes the anti-tumor activity of the EGFR TKIs, especially, theliatinib[1].

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 (theliatinib, 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

RETURN POLICY
Selleck Chemical’s Unconditional Return Policy ensures a smooth online shopping experience for our customers. If you are in any way unsatisfied with your purchase, you may return any item(s) within 7 days of receiving it. In the event of product quality issues, either protocol related or product related problems, you may return any item(s) within 365 days from the original purchase date. Please follow the instructions below when returning products.

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.

NOT FOR HUMAN, VETERINARY DIAGNOSTIC OR THERAPEUTIC USE.