Q: Do these chaperones has a different conformation when it is in the epichaperome complex? And this characteristic is used to create the probes to distinguish them when they are in the complex or not?
A: Great question. Please check PMID: 34344873 and PMID: 32610141
Q: What are the fundamental factors and mechanisms that drive or inhibit epichaperome formation?
A: Epichaperome formation is context and stressor dependent. Some stressors alone- eg. MYC hyperactivation in cancer [PMID: 27706135; PMID: 30038221], or a specific combination of stressors in vulnerable cell types, are powerful inducers.
Q: Why epichaperome formation specific to type 1 tumors? How is HSP90 in the Epichaperome different from the HSP90 pool of type 2 tumors?
A: Type 1 and 2 classification is a simple differentiation between those tumors that do express, and depend on, epichaperomes and those that do not. for how is HSP90 different, pls check PMID: 34344873 and PMID: 32610141 and PMID: 27706135
Q: How is epichaperome inhibition affected by the tumor microenvironment?
A: Great question! We published preliminary observations [PMID: 34040147; PMID: 34344873 ] so far.
Q: How small molecules act on epichaperomes selectively from the more abundant individual chaperome proteins?
A: See response to the first question.
Q: How to design a combination therapy that targets the epichaperome?
A: See PMID: 33283132 and stay tuned.
Q: Is there a natural mechanism for epichaperome elimination that somehow becomes poorly functioning?
A: Very interesting question. I don’t have an answer.
Q: Does epichaperome probe PU-H71 cross BBB?
A: No. PU-AD does [PMID: 34344873].
Q: Which companies are currently developing epichaperome inhibitors?
A: Samus therapeutics and maybe others I don’t know.
Q: Do you have many different interested parties that have shown the desire to fund target specific areas?
A: My lab is funded by NIH.
Q: How did you go about identifying chemical matter capable of modulating epichaperome interaction? And how did you measure the slow off rates?
A: Please refer to [PMID: 34344873 ] for proof-of-principle.