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VU0453595 

Cat. No. M28424
VU0453595  Structure
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Biological Activity

VU0453595 is a highly selective, systemically active M1 positive allosteric modulator (PAM, EC50=2140 nM) for the research of schizophrenia.

Chemical Information
Molecular Weight 322.34
Formula C18H15FN4O
CAS Number 1432436-13-9
Form Solid
Solubility (25°C) DMSO 100 mg/mL (ultrasonic)
Storage Powder          -20°C   3 years ;  4°C   2 years
In solvent       -80°C   6 months ;  -20°C   1 month
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] Robert W Gould, et al. Neuropsychopharmacology. Modulation of arousal and sleep/wake architecture by M1 PAM VU0453595 across young and aged rodents and nonhuman primates

[2] Sean P Moran, et al. Neuropsychopharmacology. M1-positive allosteric modulators lacking agonist activity provide the optimal profile for enhancing cognition

[3] Xiaohui Lv, et al. Neuropharmacology. M1 muscarinic activation induces long-lasting increase in intrinsic excitability of striatal projection neurons

[4] Joseph D Panarese, et al. Bioorg Med Chem Lett. Further optimization of the M1 PAM VU0453595: Discovery of novel heterobicyclic core motifs with improved CNS penetration

[5] A Ghoshal, et al. Neuropsychopharmacology. Potentiation of M1 Muscarinic Receptor Reverses Plasticity Deficits and Negative and Cognitive Symptoms in a Schizophrenia Mouse Model

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