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LY3020371 hydrochloride 

Cat. No. M28287
LY3020371 hydrochloride  Structure
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Biological Activity

LY3020371 hydrochloride is a potent, selective metabotropic glutamate 2/3 receptor (mGlu2/3) antagonist with Ki of 5.3 and 2.5 nM, potently blocks cAMP formation with IC50 of 16.2 nM. LY3020371 hydrochloride exerts an antidepressant-like signature in vivo.

Chemical Information
Molecular Weight 395.81
Formula C15H16ClF2NO5S
CAS Number 1377615-44-5
Form Solid
Solubility (25°C) DMSO 250 mg/mL (ultrasonic)
Storage 4°C, dry, sealed
Conversion of different model animals based on BSA (PMID: 27057123)
Species Mouse Rat Rabbit Guinea pig Hamster Dog
Weight (kg) 0.02 0.15 1.8 0.4 0.08 10
Body Surface Area (m2) 0.007 0.025 0.15 0.05 0.02 0.5
Km factor 3 6 12 8 5 20
Animal A (mg/kg) = Animal B (mg/kg) multiplied by  Animal B Km
Animal A Km

For example, to modify the dose of Compound A used for a mouse (20 mg/kg) to a dose based on the BSA for a rat, multiply 20 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for Compound A of 10 mg/kg.

References

[1] Jeffrey M Witkin. Pharmacol Biochem Behav. mGlu2/3 receptor antagonism: A mechanism to induce rapid antidepressant effects without ketamine-associated side-effects

[2] Nicola Hanley, et al. Sleep. Pharmacological Modulation of Sleep Homeostasis in Rat: Novel Effects of an mGluR2/3 Antagonist

[3] J M Witkin, et al. Pharmacol Biochem Behav. Preclinical predictors that the orthosteric mGlu2/3 receptor antagonist LY3020371 will not engender ketamine-associated neurotoxic, motor, cognitive, subjective, or abuse-liability-related effects

[4] Mark D Chappell, et al. J Med Chem. Discovery of (1S,2R,3S,4S,5R,6R)-2-Amino-3-[(3,4-difluorophenyl)sulfanylmethyl]-4-hydroxy-bicyclo[3.1.0]hexane-2,6-dicarboxylic Acid Hydrochloride (LY3020371·HCl): A Potent, Metabotropic Glutamate 2/3 Receptor Antagonist with Antidepressant-Like Activity

[5] Jeffrey M Witkin, et al. Neuropharmacology. In vitro pharmacological and rat pharmacokinetic characterization of LY3020371, a potent and selective mGlu2/3 receptor antagonist

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  Catalog
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