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Biotech / Medical : ARIAD Pharmaceuticals -- Ignore unavailable to you. Want to Upgrade?

To: medichem who wrote (3939)	10/9/2015 9:54:08 AM
From: tktom	Respond to of 4474

I rather doubt it will be that. Remember, Tim Clackson stated '788 will target an unmet need, and will target a unique mutation, and as you stated EGFR has a good number of competitors already, CLVS for one.

To: medichem who wrote (3939)	10/9/2015 3:13:20 PM
From: Biomaven	Respond to of 4474

It was stated to be a target that "others had tried and failed" so hard to see how EGFR fits that bill. I still believe it will be a TKI targeting the G12C KRAS mutation. >>Several FDA-approved tyrosine kinase inhibitors (e.g. afatinib, ibrutinib) take advantage of irreversible binding to a cysteine amino acid residue close to the active site. This approach inspired the development of irreversible inhibitors of KRas G12C, a specific mutant where the glycine at the 12th position of the KRas protein is mutated to cysteine (53). With sub-micromolar affinity, these inhibitors block SOS-mediated nucleotide exchange, favoring the binding of GDP instead of GTP, and rendering the KRas protein in an “off state.” When bound to KRas G12C, the compounds create a new binding surface mostly involving the switch 2 region. Importantly, they decreased viability and activated apoptosis in a KRas G12C specific lung cancer cell line. While these approaches are tantalizing, more potent drugs that bind with nanomolar affinity would be needed for a viable drug. Nevertheless, these studies provide novel lead compounds for future optimization.<< ncbi.nlm.nih.gov Peter