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

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

InChIKey

FSXCKIBROURMFT-VGSWGCGISA-N

SMILES

N1(C)CC[C@]2([H])CN(C(NC3C(OC)=CC4C(C=3)=C(NC3=CC=CC(C#C)=C3)N=CN=4)=O)C[C@]12[H]

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

Uses

Theliatinib (Xiliertinib) is a potent, ATP-competitive, orally active and highly selective EGFR inhibitor with a Ki of 0.05 nM and an IC50 of 3 nM. Theliatinib has an IC50 of 22 nM for EGFR T790M/L858R mutant. Theliatinib shows >50-fold selectivity for EGFR than other kinases[1]. Theliatinib is a click chemistry reagent, it contains an Alkyne group and can undergo copper-catalyzed azide-alkyne cycloaddition (CuAAc) with molecules containing Azide groups.

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

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

IC 50

EGFR: 3 nM (IC₅₀); EGFR: 0.05 nM (Ki); EGFR (L858R/T790M): 22 nM (IC₅₀)

References

[1] Ren Y, et al. Anti-tumor efficacy of theliatinib in esophageal cancer patient-derived xenografts models with epidermal growth factor receptor (EGFR) overexpression and gene amplification. Oncotarget. 2017 Apr 19;8(31):50832-50844. DOI:10.18632/oncotarget.17243

(3aR,6aR)-N-(4-((3-ethynylphenyl)amino)-7-methoxyquinazolin-6-yl)-1-methylhexahydropyrrolo[3,4-b]pyrrole-5(1H)-carboxamide(1353644-70-8)Related Product Information

• TG4-155
• PH 797804
• NVP-TAE684
• Axitinib
• Lapatinib
• Dasatinib
• Erlotinib
• Sunitinib
• Ruxolitinib
• AZD-9291