CNX-2006

Research use only, not for human use.

CNX-2006 is a novel irreversible mutant-selective EGFR inhibitor with IC50 of < 20 nM, with very weak inhibition at wild-type EGFR.

CNX-2006 is a potent, mutant-selective EGFR inhibitor with excellent in vitro activity in cells with activating EGFR mutations, as well as in cells harbouring the T790M mutation. CNX-2006 is the prototype for CO-1686, which is currently in a Phase I clinical trial for the treatment of EGFR-mutant lung cancer.

CNX-2006 inhibits EGFR-T790M cells growth up to 1000-fold more compared to wild-type EGFR cells. EGFR inhibition is observed in cells harbouring the T790M mutation at IC50 values below 20 nM after 1 hour exposure to the drug. CNX-2006 also significantly reduces the volume of tumor spheres derived from H1975 cells. CNX-2006 exhibits specificity and potent activity against T790M. The drug also shows activity against uncommon EGFR mutations including G719S, L861Q, an exon 19 insertion mutant (I744-K745insKIPVAI), and T854A, but not an exon 20 insertion (H773-V774HVdup). In an in vitro resistance model, CNX-2006 significantly inhibits the emergence of resistant cells. Chronic exposure to escalating doses of CNX-2006 fails to select for and/or enhance T790M-mediated resistance using PC-9 or HCC827 cells (both harboring exon 19 deletions), or PC-9/ER and HCC827/ER cells with existing T790M and resistance to erlotinib.

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CNX2006 | CNX 2006 | CNX-2006.

PI3K/Akt/mTOR signaling

mTOR

EGFR (mutant)

Cancer

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1375465-09-0

545.53

C26H27F4N7O2

>98% (HPLC)

DMSO : ≥ 52 mg/mL. 95.32 mM

COc1c(Nc2ncc(c(Nc3cccc(NC(=O)C=C)c3)n2)C(F)(F)F)ccc(NC2CN(CCF)C2)c1

N-(3-((2-((4-((1-(2-fluoroethyl)azetidin-3-yl)amino)-2-methoxyphenyl)amino)-5-(trifluoromethyl)pyrimidin-4-yl)amino)phenyl)acrylamide

(-20℃)

With Ice Pack

≥ 2 years