3 ms·

Relevant study in zebrafish/mice with this compound (MSI-1436, aka trodusquemine): https://www.nature.com/articles/s41536-017-0008-1 https://www.nature.com/arti

by radus 8y ago

Relevant study in zebrafish/mice with this compound (MSI-1436, aka trodusquemine): https://www.nature.com/articles/s41536-017-0008-1 https://www.nature.com/articles/s41536-017-0008-1.

HarryHirsch 8y ago
The compound looks like a detergent, something that would insert into cell membranes and disrupt them. Saying that it inhibits this or that kinase is really a long stretch.
- radus 8y ago
  I think that's a bit of a harsh dismissal. It's a sterol natural product that binds to PTPN1 allosterically. I've scanned the literature a bit and it seems reasonably well validated. It's termed as selective in many papers, but this is primarily referring to selectivity over a PTPN1 homolog, something which previous compounds had had trouble with.
  - HarryHirsch 8y ago
    I once worked for someone who had no clue about biology and had no critical faculties at all. She was like "but it inhibits target X", and you'd go like "and God know what else" because the compound looked far too much like a promiscuous binder. Then she'd tell you you were a pessimist. She had an Elizabeth Holmes portrait in her office until late 2016. It was a complete shitshow, like the experience of the guy behind Org Prep Daily at his startup (starts here: https://orgprepdaily.wordpress.com/2017/08/21/breakin-bad-in-florida-1/ https://orgprepdaily.wordpress.com/2017/08/21/breakin-bad-in...) minus the drug manufacturing, although I'm positive that the bosslady was on stimulants. After such an experience you get skittish. Elsethread someone mentioned a supposedly copper-binding orally active derivative. Copper-binding in stomach acid? How much of that has been validated? Part 5 of "Breaking Bad in South Florida" might be relevant: https://orgprepdaily.wordpress.com/2017/08/24/breaking-bad-in-south-florida-5/ https://orgprepdaily.wordpress.com/2017/08/24/breaking-bad-i... David Lowe has something about supposedly selective compounds polluting the literature, but I can't fidn the blogpost right now. I agree with his sentiments.

by radus 8y ago

Relevant study in zebrafish/mice with this compound (MSI-1436, aka trodusquemine): https://www.nature.com/articles/s41536-017-0008-1 https://www.nature.com/articles/s41536-017-0008-1.

HarryHirsch 8y ago

The compound looks like a detergent, something that would insert into cell membranes and disrupt them. Saying that it inhibits this or that kinase is really a long stretch.

radus 8y ago
I think that's a bit of a harsh dismissal. It's a sterol natural product that binds to PTPN1 allosterically. I've scanned the literature a bit and it seems reasonably well validated. It's termed as selective in many papers, but this is primarily referring to selectivity over a PTPN1 homolog, something which previous compounds had had trouble with.
- HarryHirsch 8y ago
  I once worked for someone who had no clue about biology and had no critical faculties at all. She was like "but it inhibits target X", and you'd go like "and God know what else" because the compound looked far too much like a promiscuous binder. Then she'd tell you you were a pessimist. She had an Elizabeth Holmes portrait in her office until late 2016. It was a complete shitshow, like the experience of the guy behind Org Prep Daily at his startup (starts here: https://orgprepdaily.wordpress.com/2017/08/21/breakin-bad-in-florida-1/ https://orgprepdaily.wordpress.com/2017/08/21/breakin-bad-in...) minus the drug manufacturing, although I'm positive that the bosslady was on stimulants. After such an experience you get skittish. Elsethread someone mentioned a supposedly copper-binding orally active derivative. Copper-binding in stomach acid? How much of that has been validated? Part 5 of "Breaking Bad in South Florida" might be relevant: https://orgprepdaily.wordpress.com/2017/08/24/breaking-bad-in-south-florida-5/ https://orgprepdaily.wordpress.com/2017/08/24/breaking-bad-i... David Lowe has something about supposedly selective compounds polluting the literature, but I can't fidn the blogpost right now. I agree with his sentiments.