KMN-159, a novel EP₄ receptor selective agonist, stimulates osteoblastic differentiation in cultured whole rat bone marrow.

ABSTRACT: KMN-159 is the lead compound from a series of novel difluorolactam prostanoid EP₄ receptor agonists aimed at inducing local bone formation while avoiding the inherent side effects of systemic EP₄ activation. KMN-159 is a potent, selective small molecule possessing pharmacokinetic properties amenable to local administration. Unfractionated rat bone marrow cells (BMCs) were treated once at plating with escalating doses of KMN-159 (1 pM to 10 μM). The resulting elevated alkaline phosphatase (ALP) levels measured 9 days post-dose are consistent with increased osteoblastic differentiation and exposure to KMN-159 at low nanomolar concentrations for as little as 30 min was sufficient to induce complete osteoblast differentiation of the BMCs from both sexes and regardless of

SUBMITTER: Owen TA 

PROVIDER: S-EPMC7416767 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature