RVX-297 -- Twice as selective for BD2 as is apabetalone
posted on
May 30, 2022 01:55PM
10-41, the only other compound that I recall them talking about was RVX-297. I have no information on their compounds outside of RVX-208 and RVX-297.
Its a compound that is twice as selective for BD2 as is apabetalone. Maybe this was the more potent compound Dr. Kulikowski referred to.
Here's the bulk of what I have on RVX-297
MUTIPLE SCLEROSIS (MS)
**** RVX-297 ****
A compound that Resverlogix is studying. Not yet tested in human trials.
http://molpharm.aspetjournals.org/content/early/2017/09/29/mol.117.110379
RVX-297 was comparable or superior to that of the S1P1 agonist FTY720 (fingolimod), 2017?
Cytokines Storms
https://clinicaltrials.gov/ct2/show/NCT04280588
http://molpharm.aspetjournals.org/content/92/6/694
RVX-297 suppressed EAE pathology when administered to mice either prophylactically or therapeutically. In addition, the production of multiple cytokines in vivo (Fig. 7) and ex vivo (Table 6) was suppressed by RVX-297. In vivo efficacy was comparable or superior to that of the S1P1 agonist FTY720 (fingolimod), an approved therapeutic agent for the treatment of MS.
https://www.ncbi.nlm.nih.gov/pubmed/28974538
SEPSIS, sepsis shock and MODS (Multiple Organ Dysfunction Syndrome)
https://agoracom.com/ir/Resverlogix/forums/discussion/topics/757053-pharmacological-modulation-of-bet-family-in-sepsis/messages/2307553#message
Excerpt :
Apabetalone and RVX-297 Apabetalone (also known as RVX-208 or RVX-000222), an oral BETi selective for BD2 within BETs, is currently used in phase 3 clinical trials for the treatment of coronary artery disease, diabetes, and chronic kidney failure. In a mouse model of lethal endotoxemia, apabetalone prevents liver damage by inhibiting the expression of alpha-2-macroglobulin and serum amyloid P. In patients with cardiovascular disease, apabetalone provides benefit for limiting chronic cytokine signaling (Wasiak et al., 2020).
Thus, this action of apabetalone might also serve as an effective therapy in treating patient with sepsis and MODS, especially sepsis-induced cardiomyopathy. BRD2 is a direct target of apabetalone (Gordon et al., 2020). Since apabetalone can inhibit the expression of angiotensin-converting enzyme 2 (ACE2), the receptor utilized by the SARS-CoV-2 particles to gain entry into human cells, it is becoming a promising drug for the treatment of COVID-19
RVX-297, a 4-quinazolinone derivative related to RVX-208, is two times more selective for BD2 than RVX-208. RVX-297 also decreases the production of multiple cytokines in endotoxemic mice (Jahagirdar et al., 2017), highlighting its potential anti-inflammatory activities in lethal infection.