I was just teaching my class about induced proximity including PROTACs. What are the current views about how serious an issue resistance is for clinical applications? #chemicalbiology - ThreadSky

About ThreadSky

laurakiessling.bsky.social • 106 days ago

I was just teaching my class about induced proximity including PROTACs. What are the current views about how serious an issue resistance is for clinical applications? #chemicalbiology

Comments

chemb.bsky.social•106 days ago

discussing how to study that with some of @trevorgraham.bsky.social ’s evolution group! I don’t think we know yet from clinical data. @krhornberger.bsky.social may be closer to that (whether he can say is another matter!). Resistance is always a problem in cancer, sadly, so suspect will be here too

chemb.bsky.social•106 days ago

A longer term approach to deal with this is to try and find an E3 that is tumour essential, so harder for the cancer to lose it or impair its function

chemb.bsky.social•106 days ago

Ciulli’s group have made dual mechanism “trivalent” degraders targeting both VHL and CRBN as a potential (if slightly crazy sounding) way round this

trevorgraham.bsky.social•106 days ago

I'm sure, sadly, that resistance will be a major issue. I would predict the two main mechanisms are modulation of the target (or up/downstream in the pathway), to prevent targeting or to compensate for the effect of target degradation, or perhaps less often modulation of the degradation machinery.

trantteam.bsky.social•106 days ago

I worry Biology will Find A Way around by upregulating something else. But...target choice will probably help ameliorate that?

Posting Rules

Be respectful to others
No spam or self-promotion
Stay on topic
Follow Bluesky's terms of service

Comments

Posting Rules

Reply