N-Formyl-Met-Leu-Phe

Biological Activity

N-Formyl-Met-Leu-Phe (fMLP) is a chemotactic peptide and a specific ligand of N-formyl peptide receptor (FPR), which can inhibit TNF-alpha secretion. N-Formyl-Met-Leu-Phe (fMLF) acts as an agonist at formyl peptide receptors (FPR; Ki = 0.8 pM). N-Formyl-Met-Leu-Phe promotes osteoblastic commitment and suppresses adipogenic commitment under osteoblastic differentiation conditions. N-Formyl-Met-Leu-Phe stimulates osteogenesis is associated with increased expression of osteogenic markers and mineralization. N-Formyl-Met-Leu-Phe inhibits expression of peroxisome proliferator-activated receptor-γ1. N-Formyl-Met-Leu-Phe promotes bone formation in zebrafish and rabbits. Treatment with N-Formyl-Met-Leu-Phe results in increased expression of Runx2. Bone marrow spaces are widely formed, and connective tissue covering bone is dense, like periosteum, in N-Formyl-Met-Leu-Phe-treated calvaria.

Conversion of different model animals based on BSA (Value based on data from FDA Draft Guidelines)

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 K_m factor for a mouse and then divide by the K_m factor for a rat. This calculation results in a rat equivalent dose for Compound A of 10 mg/kg.

Chemical Information

References

[1] Min Kyoung Shin, et al. J Biol Chem. N-formyl-methionyl-leucyl-phenylalanine (fMLP) promotes osteoblast differentiation via the N-formyl peptide receptor 1-mediated signaling pathway in human mesenchymal stem cells from bone marrow

[2] Ling-Yu Chen, et al. J Immunol. Synergistic induction of inflammation by bacterial products lipopolysaccharide and fMLP: an important microbial pathogenic mechanism

[3] G Hetland, et al. Mol Pathol. Chemotaxins C5a and fMLP induce release of calprotectin (leucocyte L1 protein) from polymorphonuclear cells in vitro

[4] P M Lad, et al. Proc Natl Acad Sci U S A. Association of the N-formyl-Met-Leu-Phe receptor in human neutrophils with a GTP-binding protein sensitive to pertussis toxin