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ML169

Cat. No. M8266
ML169 Structure
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Biological Activity

ML169 is a positive allosteric modulator (PAM) of the muscurinic acetycholine receptor M1 (CHRM1). ML169 does not cross react with other muscarinic receptors and is able to penetrate the blood brain barrier.

Chemical Information
Molecular Weight 506.34
Formula C21H17BrFN3O4S
CAS Number 1222878-02-5
Solubility (25°C) DMSO: ≥5 mg/mL
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] James C Tarr, et al. Targeting selective activation of M(1) for the treatment of Alzheimer's disease: further chemical optimization and pharmacological characterization of the M(1) positive allosteric modulator ML169

[2] Christian Wenning, et al. Left ventricular dilation and functional impairment assessed by gated SPECT are indicators of cardiac allograft vasculopathy in heart transplant recipients

[3] Thomas M Bridges, et al. Discovery and development of a second highly selective M 1 Positive Allosteric Modulator (PAM)

[4] Paul R Reid, et al. Discovery and optimization of a novel, selective and brain penetrant M1 positive allosteric modulator (PAM): the development of ML169, an MLPCN probe

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