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HTL14242

Cat. No. M28774
HTL14242 Structure
Synonym:

HTL0014242

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Quality Control & Documentation
Biological Activity

HTL14242 (HTL0014242) is an advanced and orally active mGlu5 NAM with a pKi and a pIC50 of 9.3 and 9.2, respectively. HTL14242 can be used for the research of parkinson’s disease.

Chemical Information
Molecular Weight 310.71
Formula C16H8ClFN4
CAS Number 1644645-32-8
Form Solid
Solubility (25°C) DMSO 12.5 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] Sitrarasu Vijaya Prabhu, et al. Comput Biol Chem. E-pharmacophore-based screening of mGluR5 negative allosteric modulators for central nervous system disorder

[2] Benjamin G Tehan, et al. Curr Opin Pharmacol. The use of conformationally thermostabilised GPCRs in drug discovery: application to fragment, structure and biophysical techniques

[3] Sid Topiol, et al. Bioorg Med Chem Lett. 7TM X-ray structures for class C GPCRs as new drug-discovery tools. 1. mGluR5

[4] John A Christopher, et al. J Med Chem. Fragment and Structure-Based Drug Discovery for a Class C GPCR: Discovery of the mGlu5 Negative Allosteric Modulator HTL14242 (3-Chloro-5-[6-(5-fluoropyridin-2-yl)pyrimidin-4-yl]benzonitrile)

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