Category: 571190-30-2

Randomised, open-label, multicentric phase III trial to evaluate the safety and efficacy of palbociclib in combination with endocrine therapy, guided by ESR1 mutation monitoring in oestrogen receptor-positive, HER2-negative metastatic breast cancer patients: study design of PADA-1. was written by Berger, Frédérique;Marce, Margaux;Delaloge, Suzette;Hardy-Bessard, Anne-Claire;Bachelot, Thomas;Bièche, Ivan;Pradines, Anne;De La Motte Rouge, Thibault;Canon, Jean-Luc;André, Fabrice;Arnould, Laurent;Clatot, Florian;Lemonnier, Jérôme;Marques, Sandrine;Bidard, François-Clement. And the article was included in BMJ open in 2022.Category: piperazines This article mentions the following:

INTRODUCTION: The combination of a CDK4/6 inhibitor with an aromatase inhibitor (AI) has recently become the gold standard for AI-sensitive first line treatment of oestrogen receptor-positive (ER+) HER2-negative (HER2-) advanced breast cancer. However, most patients receiving this combination will ultimately progress and require further therapies.Several studies have demonstrated that the onset of a ESR1 gene mutation lead to AIs resistance in the advanced setting. ESR1 mutations can be detected in circulating tumour DNA (ctDNA) using a digital PCR assay. Our study aims to prove the clinical efficacy of periodic monitoring for emerging or rise of ESR1 mutations in ctDNA to trigger an early change from AI plus palbociclib to fulvestrant plus palbociclib treatment while assessing global safety. METHODS: PADA-1 is a randomised, open-label, multicentric, phase III trial conducted in patients receiving AI and palbociclib as first line therapy for metastatic ER +HER2- breast cancer. 1000 patients will be included and treated with palbociclib in combination with an AI. Patients will be screened for circulating blood ESR1 mutation detection at regular intervals. Patients for whom a rising circulating ESR1 mutation is detected without tumour progression (up to N=200) will be randomised (1:1) between (1) Arm A: no modification of therapy; and (2) Arm B: palbociclib in combination with fulvestrant, a selective ER down-regulator. At tumour progression, an optional crossover will be offered to patients randomised in arm A. The coprimary endpoints are (1) Grade ≥3 haematological toxicities and their associations with baseline characteristics and (2) progression-free survival in randomised patients. ETHICS AND DISSEMINATION: The study has been approved by the French medicines agency (ANSM) and by an ethics committee (ref 01/17_1 CPP Ouest-IV Nantes) in January 2017. The trial results will be published in academic conference presentations and international peer-reviewed journals. TRIAL REGISTRATION NUMBERS: EudraCT: 2016-004360-18; NCT03079011. In the experiment, the researchers used many compounds, for example, 6-Acetyl-8-cyclopentyl-5-methyl-2-((5-(piperazin-1-yl)pyridin-2-yl)amino)pyrido[2,3-d]pyrimidin-7(8H)-one (cas: 571190-30-2Category: piperazines).

6-Acetyl-8-cyclopentyl-5-methyl-2-((5-(piperazin-1-yl)pyridin-2-yl)amino)pyrido[2,3-d]pyrimidin-7(8H)-one (cas: 571190-30-2) belongs to piperazine derivatives. Industrial applications of piperazine include the manufacture of plastics, resins, pesticides and brake fluids. Outside the body, piperazine has a remarkable power to dissolve uric acid and producing a soluble urate, but in clinical experience it has not proved equally successful. Category: piperazines

Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics

Re: Overall survival with palbociclib plus endocrine therapy versus capecitabine in postmenopausal patients with hormone receptor-positive, HER2-negative metastatic breast cancer in the PEARL study was written by Altundag, Kadri. And the article was included in European Journal of Cancer in 2022.SDS of cas: 571190-30-2 This article mentions the following:

A polemic in response to Martin et al. (Eur J Cancer 2022;168:12e24) is given. In a recent publication by Martin et al. concluded that Overall survival with palbociclib plus endocrine therapy vs. capecitabine in postmenopausal patients with hormone receptor-pos., HER2-neg. metastatic breast cancer. Specifically, the visceral metastatic burden was not described. It would be expected that tumors with a higher visceral tumor burden are less likely to be responsive to treatment. Second, weak estrogen receptor status (close similarity to triple-neg. breast cancer) has not been reported. The author concluded that these tumors seem to be more likely to be responsive to capecitabine than the palbociclib combination. In the experiment, the researchers used many compounds, for example, 6-Acetyl-8-cyclopentyl-5-methyl-2-((5-(piperazin-1-yl)pyridin-2-yl)amino)pyrido[2,3-d]pyrimidin-7(8H)-one (cas: 571190-30-2SDS of cas: 571190-30-2).

6-Acetyl-8-cyclopentyl-5-methyl-2-((5-(piperazin-1-yl)pyridin-2-yl)amino)pyrido[2,3-d]pyrimidin-7(8H)-one (cas: 571190-30-2) belongs to piperazine derivatives. Piperazine belongs to the family of medicines called anthelmintics. Piperazine is an anthelminthic especially useful in the treatment of partial intestinal obstruction caused by Ascaris worms, which is a condition primarily seen in children. Piperazine hydrate and piperazine citrate are the main anthelminthic piperazines.SDS of cas: 571190-30-2

Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics

Adverse events secondary to cetuximab therapy in head & neck cancer therapy and risk factors for serious outcomes was written by Stanbouly, Dani;Philipone, Elizabeth;Morlandt, Anthony B.;Kaleem, Arshad;Chuang, Sung-Kiang;Patel, Neel. And the article was included in Oral Oncology in 2022.Name: 6-Acetyl-8-cyclopentyl-5-methyl-2-((5-(piperazin-1-yl)pyridin-2-yl)amino)pyrido[2,3-d]pyrimidin-7(8H)-one This article mentions the following:

The objective of this study is to illustrate the adverse events secondary to cetuximab therapy for head and neck cancer and elucidate risk factors for serious outcomes. This retrospective study was conducted using the FDA Adverse Event Reporting System (FAERS). The predictor variables were patient characteristics, country of treatment, and adverse events. The outcome variable was the rate of serious outcomes. Multivariate logistic regression was created to identify all significant risk factors of the outcome. P < 0.05 was considered statistically significant. The final sample consisted of 3,086 reports of adverse events from cetuximab therapy in head and neck cancer treatment, of which 2,746 reports were considered serious (89.0%) per the FAERS criteria. Mucosal inflammation was the most common adverse event. The strongest risk factor for a serious outcome was cetuximab therapy in countries outside the US (OR 105.2, P < 0.01). Polytherapy (OR 7.6, P < 0.01) was also a risk factor for serious outcome. Health-care providers should be aware of potential complications following cetuximab administration, particularly when administered in countries outside the US and in conjunction with other medications. In the experiment, the researchers used many compounds, for example, 6-Acetyl-8-cyclopentyl-5-methyl-2-((5-(piperazin-1-yl)pyridin-2-yl)amino)pyrido[2,3-d]pyrimidin-7(8H)-one (cas: 571190-30-2Name: 6-Acetyl-8-cyclopentyl-5-methyl-2-((5-(piperazin-1-yl)pyridin-2-yl)amino)pyrido[2,3-d]pyrimidin-7(8H)-one).

6-Acetyl-8-cyclopentyl-5-methyl-2-((5-(piperazin-1-yl)pyridin-2-yl)amino)pyrido[2,3-d]pyrimidin-7(8H)-one (cas: 571190-30-2) belongs to piperazine derivatives. Piperazine causes primary dermal irritation and skin burns at high concentrations. Piperazine also causes eye irritation in humans. Piperazine is an anthelminthic especially useful in the treatment of partial intestinal obstruction caused by Ascaris worms, which is a condition primarily seen in children. Piperazine hydrate and piperazine citrate are the main anthelminthic piperazines.Name: 6-Acetyl-8-cyclopentyl-5-methyl-2-((5-(piperazin-1-yl)pyridin-2-yl)amino)pyrido[2,3-d]pyrimidin-7(8H)-one

Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics

Palbociclib negatively regulates fatty acid synthesis due to upregulation of AMPKα and miR-33a levels to increase apoptosis in Panc-1 and MiaPaCa-2 cells was written by Rencuzogullari, Ozge;Yerlikaya, Pinar Obakan;Guerkan, Ajda Coker;Arisan, Elif Damla;Telci, Dilek. And the article was included in Biotechnology and Applied Biochemistry in 2022.Name: 6-Acetyl-8-cyclopentyl-5-methyl-2-((5-(piperazin-1-yl)pyridin-2-yl)amino)pyrido[2,3-d]pyrimidin-7(8H)-one This article mentions the following:

Fatty acids (FAs) synthesis mechanism has various regulators such as fatty acid synthase (FASN), AMP-regulated protein kinase (AMPK), or mammalian target of rapamycin (mTOR), which are aberrantly dysregulated in various pancreatic cancer cells. In this study, we aim to understand the regulatory role of palbociclib, a CDK4/6 inhibitor, on the cellular energy metabolism through regulation of AMPK/mTOR signaling by modulation of intracellular miR-33a levels in Panc-1 and MiaPaCa-2 cells. Palbociclib downregulated FAs metabolism more effectively in MiaPaCa-2 cells than Panc-1 cells. Moreover, palbociclib treatment increased the levels of miR-33a in each cell line albeit a higher increase was evident in MiaPaCa-2 cells. Stress-mediated activation of mTOR signaling axis was found associated with palbociclib-mediated AMPKα activation and miR33a upregulation. These findings provided that a deeper understanding about possible interactions of cell cycle activity and reduction of FAs synthesis may facilitate the enhancement of cell death mechanisms in pancreatic cancer cells. In the experiment, the researchers used many compounds, for example, 6-Acetyl-8-cyclopentyl-5-methyl-2-((5-(piperazin-1-yl)pyridin-2-yl)amino)pyrido[2,3-d]pyrimidin-7(8H)-one (cas: 571190-30-2Name: 6-Acetyl-8-cyclopentyl-5-methyl-2-((5-(piperazin-1-yl)pyridin-2-yl)amino)pyrido[2,3-d]pyrimidin-7(8H)-one).

6-Acetyl-8-cyclopentyl-5-methyl-2-((5-(piperazin-1-yl)pyridin-2-yl)amino)pyrido[2,3-d]pyrimidin-7(8H)-one (cas: 571190-30-2) belongs to piperazine derivatives. Piperazine was first introduced as an anthelmintic in 1953. Piperazine compounds mediate their anthelmintic action by generally paralyzing parasites, allowing the host body to easily remove or expel the invading organism. Piperazine and its salts did not induce point mutations in a bacterial test. A series of mutagenicity studies in cells, both in vitro and in vivo, has been completed and showed no evidence of mutagenic effect.Name: 6-Acetyl-8-cyclopentyl-5-methyl-2-((5-(piperazin-1-yl)pyridin-2-yl)amino)pyrido[2,3-d]pyrimidin-7(8H)-one

Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics