Famlasertib is a potent, brain-penetrant MAP4K inhibitor with IC50 s value of 0.3 nM, 23.7 nM, and 44.7 nM for HGK (MAP4K4), MLK3, and MLK1, respectively. Famlasertib shows motor neuron protection and anti-inflammatory properties. Famlasertib can be used for the study of amyotrophic lateral sclerosis (ALS) [1] [2].
In Vivo, Famlasertib (Prostetin/12k; 10 mg/kg; intraperitoneal injection or oral gavage; mice) greatly increases the area under the curve (AUC). The concentration of Famlasertib in the brain is increased across all time points and routes of administration assessed, as were brain-to-plasma ratios, indicating improved brain penetrance. The oral bioavailability (%F) for Famlasertib is 73[1].
In Vitro, Famlasertib (Prostetin/12k) rescues Cyclopiazonic acid -induced neurodegeneration with an EC50 of 0.1 μM in motor neuron survival assay[1]. Famlasertib significantly decreases TNFα secretion with an EC50 of ~0.47 μM, in Lipopolysaccharides (LPS)-stimulated microglia[1].
References:
[1]. Bos PH, et al. Development of MAP4 Kinase Inhibitors as Motor Neuron-Protecting Agents. Cell Chem Biol. 2019 Dec 19;26(12):1703-1715.e37.
[2]. Moreno R, et al. The emerging role of mixed lineage kinase 3 (MLK3) and its potential as a target for neurodegenerative diseases therapies. Eur J Med Chem. 2023 Sep 5;257:115511.
In Vivo, Famlasertib (Prostetin/12k; 10 mg/kg; intraperitoneal injection or oral gavage; mice) greatly increases the area under the curve (AUC). The concentration of Famlasertib in the brain is increased across all time points and routes of administration assessed, as were brain-to-plasma ratios, indicating improved brain penetrance. The oral bioavailability (%F) for Famlasertib is 73[1].
In Vitro, Famlasertib (Prostetin/12k) rescues Cyclopiazonic acid -induced neurodegeneration with an EC50 of 0.1 μM in motor neuron survival assay[1]. Famlasertib significantly decreases TNFα secretion with an EC50 of ~0.47 μM, in Lipopolysaccharides (LPS)-stimulated microglia[1].
References:
[1]. Bos PH, et al. Development of MAP4 Kinase Inhibitors as Motor Neuron-Protecting Agents. Cell Chem Biol. 2019 Dec 19;26(12):1703-1715.e37.
[2]. Moreno R, et al. The emerging role of mixed lineage kinase 3 (MLK3) and its potential as a target for neurodegenerative diseases therapies. Eur J Med Chem. 2023 Sep 5;257:115511.