Category: 1443437-74-8

Electric Literature of 1443437-74-8, The reaction rate of a catalyzed reaction is faster than the reaction rate of the uncatalyzed reaction at the same temperature.1443437-74-8, Name is CCG-203971, molecular formula is C23H21ClN2O3. In a Article，once mentioned of 1443437-74-8

We recently reported the development of a novel inhibitor of Rho-mediated gene transcription (1, CCG-203971) that is efficacious in multiple animal models of acute fibrosis, including scleroderma, when given intraperitoneally. The modest in vivo potency and poor pharmacokinetics (PK) of this lead, however, make it unsuitable for long term efficacy studies. We therefore undertook a systematic medicinal chemistry effort to improve both the metabolic stability and the solubility of 1, resulting in the identification of two analogs achieving over 10-fold increases in plasma exposures in mice. We subsequently showed that one of these analogs (8f, CCG-232601) could inhibit the development of bleomycin-induced dermal fibrosis in mice when administered orally at 50 mg/kg, an effect that was comparable to what we had observed earlier with 1 at a 4-fold higher IP dose.

A reaction mechanism is the microscopic path by which reactants are transformed into products. Each step is an elementary reaction. In my other articles, you can also check out more blogs about 1443437-74-8

Reference：
Piperidine – Wikipedia,
Piperidine | C5H23947N – PubChem

 

Chemistry is an experimental science, Computed Properties of C23H21ClN2O3, and the best way to enjoy it and learn about it is performing experiments.Introducing a new discovery about 1443437-74-8, Name is CCG-203971

Pharmacological inhibition of myocardin-related transcription factor pathway blocks lung metastases of RhoC-Overexpressing melanoma

Melanoma is the most dangerous form of skin cancer with the majority of deaths arising from metastatic disease. Evidence implicates Rho-activated gene transcription in melanoma metastasis mediated by the nuclear localization of the transcriptional coactivator, myocardin-related transcription factor (MRTF). Here, we highlight a role for Rho and MRTF signaling and its reversal by pharmacologic inhibition using in vitro and in vivo models of human melanoma growth and metastasis. Using two cellular models of melanoma, we clearly show that one cell type, SK-Mel-147, is highly metastatic, has high RhoC expression, and MRTF nuclear localization and activity. Conversely, SK-Mel-19 melanoma cells have low RhoC expression, and decreased levels of MRTF-regulated genes. To probe the dependence of melanoma aggressiveness to MRTF transcription, we use a previously developed smallmolecule inhibitor, CCG-203971, which at low micromolar concentrations blocks nuclear localization and activity of MRTF-A. In SK-Mel-147 cells, CCG-203971 inhibits cellular migration and invasion, and decreases MRTF target gene expression. In addition, CCG-203971-mediated inhibition of the Rho/MRTF pathway significantly reduces cell growth and clonogenicity and causes G1 cell-cycle arrest. In an experimental model of melanoma lung metastasis, the RhoC-overexpressing melanoma cells (SK-Mel-147) exhibited pronounced lung colonization compared with the low RhoC-expressing SK-Mel-19. Furthermore, pharmacologic inhibition of the MRTF pathway reduced both the number and size of lung metastasis resulting in a marked reduction of total lung tumor burden. These data link Rho and MRTF-mediated signaling with aggressive phenotypes and support targeting the MRTF transcriptional pathway as a novel approach to melanoma therapeutics.

Sometimes chemists are able to propose two or more mechanisms that are consistent with the available data. Computed Properties of C23H21ClN2O3, If a proposed mechanism predicts the wrong experimental rate law, however, the mechanism must be incorrect.Welcome to check out more blogs about 1443437-74-8, in my other articles.

Reference£º
Piperidine – Wikipedia,
Piperidine | C5H23949N – PubChem