SERx – 500 Series

Our SERx – 500 series chemotype has a unique profile with 5HT1A, 5HT2C, and 5HT7 receptor partial agonist activity. Our lead compound, SERx – 519, is highly effective in decreasing repetitive behaviors and motor stereotypy, and increasing social functioning in multiple Fragile X syndrome and autism mouse models, suggesting efficacy in treating core Fragile X symptoms. Partial activation of 5HT1A receptors alleviates stereotyped (repetitive) behaviors and social anxiety, while partial activation of 5HT2C and 5HT7 receptors produces pro-cognitive effects. Importantly, we have achieved this high 5HT1A/2C/7 selective activation with minimal effects at other receptors, which represents a unique receptor modulation profile—no other drug class achieves this. We anticipate that our lead will have minimal side effects, such as suppression of locomotor activity, sedative/stimulant activity, or cognitive impairment seen with other drugs.

We have evaluated the SERx – 519 in multiple animal models:

S5-1

SERx – 519 attenuates (abolishes) repetitive jumping in mouse models of Fragile X syndrome and autism spectrum disorder.


SERx – 519 has no detectable effect on normal locomotor behavior in FXS/ASD (C58J) or Wild-type (C57J) mice.


SERx – 519 attenuates effects of dizoclipine (MK801), a glutamate antagonist that induces repetitive circling behavior and cognitive dysfunction in mice.


SERx – 519 attenuates effects of dimethoxyiodoamphetamine (DOI), a serotonin agonist that induces repetitive head-twitching in mice.


SERx – 519  increases social behaviors and decreases unproductive compulsive behaviors (obsessive grooming) in mice.


A head-to-head comparison of SERx – 519 vs. buspirone was conducted.  SERx – 519, like buspirone, attenuates repetitive behavior in a mouse model of tics/head-twitch.  However, in contrast to buspirone, SERx – 519 does not significantly depress locomotor activity (no sedative effect).