(3aR,6aR)-N-(4-((3-ethynylphenyl)amino)-7-methoxyquinazolin-6-yl)-1-methylhexahydropyrrolo[3,4-b]pyrrole-5(1H)-carboxamide Property

Boiling point:

675.6±55.0 °C(Predicted)

Density 

1.35±0.1 g/cm3(Predicted)

storage temp. 

Store at -20°C

solubility 

DMSO: 5 mg/mL (11.30 mM)

pka

13.59±0.20(Predicted)

form 

Solid

color 

White to off-white

Hazard and Precautionary Statements (GHS)

(3aR,6aR)-N-(4-((3-ethynylphenyl)amino)-7-methoxyquinazolin-6-yl)-1-methylhexahydropyrrolo[3,4-b]pyrrole-5(1H)-carboxamide Chemical Properties,Usage,Production

Biological Activity

Theliatinib (HMPL-309) is a potent EGFR inhibitor with a Ki value of 0.05 nM for EGFR and IC50 values of 3 nM and 22 nM for EGFR and EGFR T790M/L858R mutant, respectively. It is more than 50-fold selective for EGFR over 72 other kinases.

in vitro

Compared with erlotinib or gefitnib, theliatinib has stronger binding affinity to wild-type EGFR and is more difficult to be replaced by ATP, which makes theliatinib have better target binding effect, and the EGFR-activated tumors have stronger antitumor activity.

in vivo

Theliatinib has concentration-dependent antitumor activity in a series of patient-derived esophageal cancer xenograft models. But aberrant activation or genetic mutation of other targets such as PI3K and FGFR attenuates the antitumor activity of EGFR inhibitors, especially theliatinib.

target

< td style="border-bottom: 1px dotted #ccc;padding: 5px;"> 3 nM

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