Work with LifeSpan to design a custom immunohistochemistry to address your specific biological question. Outsource the entire localization process without having to
worry about finding and characterizing target specific antibodies, sourcing and validating difficult-to-find tissues, and having the ability to interpret the resulting
immunostaining in relation to complex human pathologies.
TCR Screening Services
Test your therapeutic antibodies in immunohistochemistry against a broad panel of normal frozen human tissue types in order to determine potential unintended binding.
Our non-GLP TCR services are designed on the FDA recommendation outlined in their "Points to Consider in the Manufacture and Testing of Monoclonal Antibody Products for Human Use".
Description: The prostaglandin E receptor 4 (EP4) is one of four G protein-coupled receptors that mediate the actions of prostaglandin E2 (PGE2). Binding of PGE2 to the EP4 receptor causes an increase in intracellular cyclic AMP, which plays important roles in bone formation and resorption, cancer, and atherosclerosis. KMN-80 is a substituted gamma -lactam (pyrrolidinone) derivative of PGE1 that acts as a selective and potent agonist of EP4 with an IC50 value of 3 nM (IC50 = 1.4 µM for EP3 and > 10 µM for all other prostanoid receptors). In functional assays it has been shown to stimulate secreted alkaline phosphatase gene reporter activity in EP4-transfected HEK293 cells with an EC50 value of 0.19 nM, demonstrating >5,000 and 50,000-fold selectivity against EP2 and TP, respectively. KMN-80 can induce the differentiation of bone marrow stem cells from both young and aged rats into osteoblasts in vitro (EC50s = 20 and 153 nM, respectively) and exhibits favorable tolerability up to at least 10 µM, whereas the EP4 agonist L-902,688 is highly cytotoxic at similar concentrations in these cells.
KMN-80 is supplied as a solution in ethanol. To change the solvent, simply evaporate the ethanol under a gentle stream of nitrogen and immediately add the solvent of choice. Solvents such as et DMSO and dimethyl formamide, purged with an inert gas can be used. The solubility of KMN-80 in these solvents is approximately 15 and 20 mg/ml, respectively. KMN-80 is sparingly soluble in aqueous buffers. For maximum solubility in aqueous buffers, the ethanolic solution of KMN-80 should be diluted with the aqueous buffer of choice. KMN-80 has a solubility of approximately 0.5 mg/ml in a 1:1 solution of ethanol:PBS (pH 7.2) using this method. We do not recommend storing the aqueous solution for more than one day.
Li, M., Thompson, D.D., and Paralkar, V.M. Int. Orthop. 31, 767-772 (2007).
Hawcroft, G., Ko, C.W.S., and Hull, M.A. Oncogene 26, 3006-3019 (2007).