Tag: 434.5373

Ribociclib efficacy in special populations and analysis of patient-reported outcomes in the MONALEESA trials was written by Sano, Maria V.;Martorana, Federica;Lavenia, Giuseppe;Rossello, Rosalba;Prestifilippo, Angela;Sava, Serena;Ricciardi, Giuseppina R.;Vigneri, Paolo. And the article was included in Expert Review of Anticancer Therapy in 2022.Recommanded Product: 1211441-98-3 This article mentions the following:

Cyclin-dependent kinase 4/6 (CDK4/6) inhibitors abemaciclib, palbociclib, and ribociclib radically modified the treatment of hormone receptor-pos./human epidermal growth factor 2-neg. advanced breast cancer. Ribociclib efficacy was proved in the phase III MONALEESA-2, -3, and -7 trials. In the first-line setting, ribociclib plus endocrine therapy determined statistically significant improvements in progression-free (PFS) and overall survival (OS) in pre-menopausal (MONALEESA-7) and post-menopausal (MONALEESA-2) women. Likewise, ribociclib and fulvestrant induced a significant PFS and OS benefit in post-menopausal women previously treated with endocrine therapy (MONALEESA-3). Addnl., ribociclib did not affect patients health-related quality of life in all the MONALEESA trials. We reviewed the results of the available randomized phase III trials testing ribociclib and endocrine therapy in advanced breast cancer, focusing on different patient subgroups and then on health-related quality of life. The benefit of ribociclib is consistent across patient subgroups and is maintained in populations with unfavorable features, such as those with endocrine resistance or visceral metastases. Furthermore, the addition of ribociclib to endocrine therapy delays quality of life deterioration and improves pain scores. These results represent a pivotal improvement for the treatment of advanced breast cancer patients receiving CDK4/6 inhibitors. In the experiment, the researchers used many compounds, for example, 7-Cyclopentyl-N,N-dimethyl-2-((5-(piperazin-1-yl)pyridin-2-yl)amino)-7H-pyrrolo[2,3-d]pyrimidine-6-carboxamide (cas: 1211441-98-3Recommanded Product: 1211441-98-3).

7-Cyclopentyl-N,N-dimethyl-2-((5-(piperazin-1-yl)pyridin-2-yl)amino)-7H-pyrrolo[2,3-d]pyrimidine-6-carboxamide (cas: 1211441-98-3) 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. Two common salts in the form of which piperazine is usually prepared for pharmaceutical or veterinary purposes are the citrate, 3C4H10N2.2C6H8O7 (i.e. containing 3 molecules of piperazine to 2 molecules of citric acid), and the adipate, C4H10N2.C6H10O4 (containing 1 molecule each of piperazine and adipic acid).Recommanded Product: 1211441-98-3

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

Differential Inhibition of Equilibrative Nucleoside Transporter 1 (ENT1) Activity by Tyrosine Kinase Inhibitors was written by Jouan, Elodie;Moreau, Amelie;Bruyere, Arnaud;Alim, Karima;Denizot, Claire;Parmentier, Yannick;Fardel, Olivier. And the article was included in European Journal of Drug Metabolism and Pharmacokinetics in 2021.Product Details of 1211441-98-3 This article mentions the following:

Equilibrative nucleoside transporter (ENT) 1 is a widely-expressed drug transporter, handling nucleoside analogs as well as endogenous nucleosides. ENT1 has been postulated to be inhibited by some marketed tyrosine kinase inhibitors (TKIs). To obtain insights into this point, the interactions of 24 TKIs with ENT1 activity have been analyzed. Inhibition of ENT1 activity was investigated in vitro through quantifying the decrease of [³H]-uridine uptake caused by TKIs in HAP1 ENT2-knockout cells, exhibiting selective ENT1 expression. TKI effects towards ENT1-mediated transport were addnl. characterized in terms of their in vivo relevance and of their relationship to TKI mol. descriptors. Putative transport of the TKI lorlatinib by ENT1/ENT2 was analyzed by LC-MS/MS. Of 24 TKIs, 12 of them, each used at 10μM, were found to behave as moderate or strong inhibitors of ENT1, i.e., they decreased ENT1 activity by at least 35%. This inhibition was concentration-dependent for at least the strongest ones (IC₅₀ less than 10μM) and was correlated with some mol. descriptors, especially with atom-type E-state indexes. Lorlatinib was notably a potent in vitro inhibitor of ENT1/ENT2 (IC₅₀ values around 1.0-2.5μM) and was predicted to inhibit these nucleoside transporters at relevant clin. concentrations, without, however, being a substrate for them. Our data unambiguously add ENT1 to the list of drug transporters inhibited by TKIs, especially by lorlatinib. This point likely merits attention in terms of possible drug-drug interactions, notably for nucleoside analogs, whose ENT1-mediated uptake into their target cells may be hampered by co-administrated TKIs such as lorlatinib. In the experiment, the researchers used many compounds, for example, 7-Cyclopentyl-N,N-dimethyl-2-((5-(piperazin-1-yl)pyridin-2-yl)amino)-7H-pyrrolo[2,3-d]pyrimidine-6-carboxamide (cas: 1211441-98-3Product Details of 1211441-98-3).

7-Cyclopentyl-N,N-dimethyl-2-((5-(piperazin-1-yl)pyridin-2-yl)amino)-7H-pyrrolo[2,3-d]pyrimidine-6-carboxamide (cas: 1211441-98-3) 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. Two common salts in the form of which piperazine is usually prepared for pharmaceutical or veterinary purposes are the citrate, 3C4H10N2.2C6H8O7 (i.e. containing 3 molecules of piperazine to 2 molecules of citric acid), and the adipate, C4H10N2.C6H10O4 (containing 1 molecule each of piperazine and adipic acid).Product Details of 1211441-98-3

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

Clinical CDK4/6 inhibitors induce selective and immediate dissociation of p21 from cyclin D-CDK4 to inhibit CDK2 was written by Pack, Lindsey R.;Daigh, Leighton H.;Chung, Mingyu;Meyer, Tobias. And the article was included in Nature Communications in 2021.Category: piperazines This article mentions the following:

Since their discovery as drivers of proliferation, cyclin-dependent kinases (CDKs) have been considered therapeutic targets. Small mol. inhibitors of CDK4/6 are used and tested in clin. trials to treat multiple cancer types. Despite their clin. importance, little is known about how CDK4/6 inhibitors affect the stability of CDK4/6 complexes, which bind cyclins and inhibitory proteins such as p21. We develop an assay to monitor CDK complex stability inside the nucleus. Unexpectedly, treatment with CDK4/6 inhibitors-palbociclib, ribociclib, or abemaciclib-immediately dissociates p21 selectively from CDK4 but not CDK6 complexes. This effect mediates indirect inhibition of CDK2 activity by p21 but not p27 redistribution. Our work shows that CDK4/6 inhibitors have two roles: non-catalytic inhibition of CDK2 via p21 displacement from CDK4 complexes, and catalytic inhibition of CDK4/6 independent of p21. By broadening the non-catalytic displacement to p27 and CDK6 containing complexes, next-generation CDK4/6 inhibitors may have improved efficacy and overcome resistance mechanisms. In the experiment, the researchers used many compounds, for example, 7-Cyclopentyl-N,N-dimethyl-2-((5-(piperazin-1-yl)pyridin-2-yl)amino)-7H-pyrrolo[2,3-d]pyrimidine-6-carboxamide (cas: 1211441-98-3Category: piperazines).

7-Cyclopentyl-N,N-dimethyl-2-((5-(piperazin-1-yl)pyridin-2-yl)amino)-7H-pyrrolo[2,3-d]pyrimidine-6-carboxamide (cas: 1211441-98-3) belongs to piperazine derivatives. Piperazine causes primary dermal irritation and skin burns at high concentrations. Piperazine also causes eye irritation in humans. Intermediate for a wide range of pharmaceuticals, polymers, dyes, corrosion inhibitors, rubber accelerators and surfactants.Category: piperazines

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

Real-World Outcomes of Ribociclib and Aromatase Inhibitor Use in First Line Hormone Receptor Positive, HER2-Negative Metastatic Breast Cancer was written by Wong, Vanessa;de Boer, Richard;Baron-Hay, Sally;Blum, Robert;Boyle, Frances;Chua, Susan;Clarke, Kerrie;Cuff, Katharine;Green, Michael;Lim, Elgene;Mok, Kelly;Nott, Louise;Nottage, Michelle;Tafreshi, Ali;Tsoi, Daphne;Uccellini, Anthony;Hong, Wei;Gibbs, Peter;Lok, Sheau Wen. And the article was included in Clinical Breast Cancer.Electric Literature of C23H30N8O This article mentions the following:

International guidelines recommend combining a CDK4/6 inhibitor and endocrine therapy (ET) as first line treatment for hormone receptor (HR) pos., HER2 neg. metastatic breast cancer (MBC). Results from MONALEESA-2 demonstrate superior progression free survival (PFS) and overall survival (OS) with ribociclib (CDK4/6 inhibitor) and ET compared to ET alone. Real world outcomes have yet to be reported.KARMA is a non-interventional registry of Australian patients receiving first-line treatment with ribociclib and aromatase inhibitor (AI), obtained via a Medicine Access Program (MAP) for HR+, HER2- MBC. Outcomes were compared with the ribociclib/letrozole cohort in MONALEESA-2.Data from 160 patients at 17 sites was analyzed. Median follow-up is 36.5 mo. Compared to MONALEESA-2, patients were numerically younger (54.3 vs. 62 years), with higher rates of bone-only metastases (31% vs. 21%). A total of 63 of 160 (39%) patients remain on treatment. A total of 56% of patients had at least 1 dose reduction, with neutropenia (68%) and abnormal liver enzymes (17%) the most common reasons. A total of 17 of 160 (11%) discontinued treatment due to toxicity, with no treatment related deaths. Median PFS was not reached (95% CI 29.9- NR), with PFS at 12 mo and 18 mo being 76% and 67% resp. vs. 25.3 mo, 73% and 63% in MONALEESA-2.The ribociclib and AI combination was well tolerated in this real-world setting. The KARMA registry cohort achieved a superior PFS (>36.5 mo) to MONALEESA-2, potentially due to more favorable baseline disease characteristics. Less frequent assessment scheduling in this non trial setting may also contribute. In the experiment, the researchers used many compounds, for example, 7-Cyclopentyl-N,N-dimethyl-2-((5-(piperazin-1-yl)pyridin-2-yl)amino)-7H-pyrrolo[2,3-d]pyrimidine-6-carboxamide (cas: 1211441-98-3Electric Literature of C23H30N8O).

7-Cyclopentyl-N,N-dimethyl-2-((5-(piperazin-1-yl)pyridin-2-yl)amino)-7H-pyrrolo[2,3-d]pyrimidine-6-carboxamide (cas: 1211441-98-3) belongs to piperazine derivatives. Industrial applications of piperazine include the manufacture of plastics, resins, pesticides and brake fluids. Although many piperazine derivatives occur naturally, piperazine itself can be synthesized by reacting alcoholic ammonia with 1,2-dichloroethane, by the action of sodium and ethylene glycol on ethylene diamine hydrochloride, or by reduction of pyrazine with sodium in ethanol.Electric Literature of C23H30N8O

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

War against NRAS-mutant melanoma using targeted therapies remains challenging was written by Moschos, Stergios J.. And the article was included in Clinical Cancer Research in 2022.Product Details of 1211441-98-3 This article mentions the following:

In the search for targeting MAPK plus other pathways in NRAS-mutant melanoma, a phase Ib/II trial tested binimetinib plus ribociclib in metastatic melanoma. The response rate in the phase II trial was 19.5%, and the median progression-free survival was 3.7 mo. In the experiment, the researchers used many compounds, for example, 7-Cyclopentyl-N,N-dimethyl-2-((5-(piperazin-1-yl)pyridin-2-yl)amino)-7H-pyrrolo[2,3-d]pyrimidine-6-carboxamide (cas: 1211441-98-3Product Details of 1211441-98-3).

7-Cyclopentyl-N,N-dimethyl-2-((5-(piperazin-1-yl)pyridin-2-yl)amino)-7H-pyrrolo[2,3-d]pyrimidine-6-carboxamide (cas: 1211441-98-3) belongs to piperazine derivatives. Piperazine is a fairly basic compound and is an amine solvent. Piperazine is formed as a co-product in the ammoniation of 1,2-dichloroethane or ethanolamine. These are the only routes to the chemical used commercially.Product Details of 1211441-98-3

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