The small molecule AMBMP disrupts microtubule growth, ciliogenesis, cell polarity, and cell migration

Abstract

2-Amino-4-(3,4-(methylenedioxy)benzylamino)-6-(3-methoxyphenyl)pyrimidine (AMBMP) is a small molecule that has been previously reported to be both a Wnt agonist and a microtubule (MT) regulator. Here we report a detailed analysis of AMBMPs effects on MTs and on MT associated cellular processes including cell polarity, ciliogenesis, and cell migration. Specifically, treatment of Xenopus embryos with AMBMP leads to defects similar to the MT depolymerizing drug nocodazole, including a failure to generate or polarize cilia (depending on the timing of treatment) and a loss of the cell movements associated with radial intercalation. The dramatic effect AMBMP has on basic MT based cellular functions suggests that its usefulness as a Wnt regulator is questionable. Moreover, it may be an important new tool for experimental or pharmacological manipulation of MTs.

A Small-Molecule Approach to Restore a Slow-Oxidative Phenotype and Defective CaMKIIβ Signaling in Limb Girdle Muscular Dystrophy

“…AMBMP is toxic to cells at high concentrations in vitro , due to its microtubule binding activity. 41 We also observed similar toxicity in vitro , but this finding did not translate to the in vivo setting. Similarly, AMBMP has been used as a Wnt agonist in several in vivo studies without toxicity.…”

Pluripotent Core in Bovine Embryos: A Review

“…Denicol et al [40] observed that activation of canonical WNT signaling with the agonist AMBMP from day 5, disturbed development until the blastocyst stage and reduced the numbers of TE and ICM cells. This was not surprising, since this molecule also disrupts microtubule organization [58]. Another study observed that blocking GSK3 with CHIR99021 (3 µM) from the morula stage onwards improved blastocyst morphology and epiblast-specific gene expression (NANOG, SOX2) [59].…”

Pluripotent Core in Bovine Embryos: A Review

“…Denicol et al [40] observed that activation of canonical WNT signaling with the agonist AMBMP from day 5, disturbed the development until blastocyst stage and reduced the number of TE and ICM cells. This is not surprising since this molecule also disrupts microtubule organization [55]. Another study observed that blocking GSK3 with CHIR99021 (3 µM) from morula stage onwards improved blastocyst morphology and epiblast-specific gene expression (NANOG, SOX2) [56].…”