Tag: 447.5328

Switch to fulvestrant and palbociclib versus no switch in advanced breast cancer with rising ESR1 mutation during aromatase inhibitor and palbociclib therapy (PADA-1): a randomised, open-label, multicentre, phase 3 trial was written by Bidard, Francois-Clement;Hardy-Bessard, Anne-Claire;Dalenc, Florence;Bachelot, Thomas;Pierga, Jean-Yves;de la Motte Rouge, Thibault;Sabatier, Renaud;Dubot, Coraline;Frenel, Jean-Sebastien;Ferrero, Jean Marc;Ladoire, Sylvain;Levy, Christelle;Mouret-Reynier, Marie-Ange;Lortholary, Alain;Grenier, Julien;Chakiba, Camille;Stefani, Laetitia;Plaza, Jerome Edouard;Clatot, Florian;Teixeira, Luis;D′Hondt, Veronique;Vegas, Helene;Derbel, Olfa;Garnier-Tixidre, Claire;Canon, Jean-Luc;Pistilli, Barbara;Andre, Fabrice;Arnould, Laurent;Pradines, Anne;Bieche, Ivan;Callens, Celine;Lemonnier, Jerome;Berger, Frederique;Delaloge, Suzette. And the article was included in Lancet Oncology in 2022.Recommanded Product: 571190-30-2 This article mentions the following:

In advanced estrogen receptor-pos., HER2-neg. breast cancer, acquired resistance to aromatase inhibitors frequently stems from ESR1-mutated subclones, which might be sensitive to fulvestrant. The PADA-1 trial aimed to show the efficacy of an early change in therapy on the basis of a rising ESR1 mutation in blood (bESR1^mut), while assessing the global safety of combination fulvestrant and palbociclib. We did a randomised, open-label, phase 3 trial in 83 hospitals in France. Women aged at least 18 years with estrogen receptor-pos., HER2-neg. advanced breast cancer and an Eastern Cooperative Oncol. Group performance status of 0-2 were recruited and monitored for rising bESR1^mut during first-line aromatase inhibitor (2·5 mg letrozole, 1 mg anastrozole, or 25 mg exemestane, orally once per day, taken continuously) and palbociclib (125 mg orally once per day on days 1-21 of a 28-day cycle) therapy. Patients with newly present or increased bESR1^mut in circulating tumor DNA and no synchronous disease progression were randomly assigned (1:1) to continue with the same therapy or to switch to fulvestrant (500 mg i.m. on day 1 of each 28-day cycle and on day 15 of cycle 1) and palbociclib (dosing unchanged). The randomisation sequence was generated within an interactive web response system using a minimisation method (with an 80% random factor); patients were stratified according to visceral involvement (present or absent) and the time from inclusion to bESR1^mut detection (<12 mo or ≥12 mo). The co-primary endpoints were investigator-assessed progression-free survival from random assignment, analyzed in the intention-to-treat population (ie, all randomly assigned patients), and grade 3 or worse haematol. adverse events in all patients. The trial is registered with Clinicaltrials.gov (NCT03079011), and is now complete. From March 22, 2017, to Jan 31, 2019, 1017 patients were included, of whom 279 (27%) developed a rising bESR1^mut and 172 (17%) were randomly assigned to treatment: 88 to switching to fulvestrant and palbociclib and 84 patients to continuing aromatase inhibitor and palbociclib. At database lock on July 31, 2021, randomly assigned patients had a median follow-up of 35·3 mo (IQR 29·2-41·4) from inclusion and 26·0 mo (13·8-34·3) from random assignment. Median progression-free survival from random assignment was 11·9 mo (95% CI 9·1-13·6) in the fulvestrant and palbociclib group vs. 5·7 mo (3·9-7·5) in the aromatase inhibitor and palbociclib group (stratified HR 0·61, 0·43-0·86; p=0·0040). The most frequent grade 3 or worse haematol. adverse events were neutropenia (715 [70·3%] of 1017 patients), lymphopenia (66 [6·5%]), and thrombocytopenia (20 [2·0%]). The most common grade 3 or worse adverse events in step 2 were neutropenia (35 [41·7%] of 84 patients in the aromatase inhibitor and palbociclib group vs 39 [44·3%] of 88 patients in the fulvestrant and palbociclib group) and lymphopenia (three [3·6%] vs four [4·5%]). 31 (3·1%) patients had grade 3 or worse serious adverse events related to treatment in the overall population. Three (1·7%) of 172 patients randomly assigned had one serious adverse event in step 2: one (1·2%) grade 4 neutropenia and one (1·2%) grade 3 fatigue among 84 patients in the aromatase inhibitor and palbociclib group, and one (1·1%) grade 4 neutropenia among 88 patients in the fulvestrant and palbociclib group. One death by pulmonary embolism in step 1 was declared as being treatment related. PADA-1 is the first prospective randomised trial showing that the early therapeutic targeting of bESR1^mut results in significant clin. benefit. Addnl., the original design explored in PADA-1 might help with tackling acquired resistance with new drugs in future trials.Pfizer. 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: 571190-30-2Recommanded Product: 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 is a fairly basic compound and is an amine solvent. 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.Recommanded Product: 571190-30-2

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

Enhanced O-GlcNAc modification induced by the RAS/MAPK/CDK1 pathway is required for SOX2 protein expression and generation of cancer stem cells was written by Shimizu, Masahiro;Shibuya, Hiroshi;Tanaka, Nobuyuki. And the article was included in Scientific Reports in 2022.SDS of cas: 571190-30-2 This article mentions the following:

Cancer stem cells (CSCs) have tumor initiation, self-renewal, and long-term tumor repopulation properties, and it is postulated that differentiated somatic cells can be reprogrammed to CSCs by oncogenic signals. We previously showed that oncogenic HRASV12 conferred tumor initiation capacity in tumor suppressor p53-deficient (p53-/-) primary mouse embryonic fibroblasts (MEFs) through transcription factor NF-κB-mediated enhancement of glucose uptake; however, the underlying mechanisms of RAS oncogene-induced CSC reprogramming have not been elucidated. Here, we found that the expression of the reprogramming factor SOX2 was induced by HRASV12 in p53-/- MEFs. Moreover, gene knockout studies revealed that SOX2 is an essential factor for the generation of CSCs by HRASV12 in mouse and human fibroblasts. We demonstrated that HRASV12-induced cyclin-dependent kinase 1 (CDK1) activity and subsequent enhancement of protein O-GlcNAcylation were required for SOX2 induction and CSC generation in these fibroblasts and cancer cell lines containing RAS mutations. Moreover, the CDK inhibitor dinaciclib and O-GlcNAcylation inhibitor OSMI1 reduced the number of CSCs derived from these cells. Taken together, our results reveal a signalling pathway and mechanism for CSC generation by oncogenic RAS and suggest the possibility that this signalling pathway is a therapeutic target for CSCs. 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 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. Piperazines are very broad chemical group, covering a wide range of drugs from antidepressants to antihistamines. The connecting property of all these chemicals is the presence of a piperazine functional group.SDS of cas: 571190-30-2

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

Proteomic profiling reveals CDK6 upregulation as a targetable resistance mechanism for lenalidomide in multiple myeloma was written by Ng, Yuen Lam Dora;Ramberger, Evelyn;Bohl, Stephan R.;Dolnik, Anna;Steinebach, Christian;Conrad, Theresia;Mueller, Sina;Popp, Oliver;Kull, Miriam;Haji, Mohamed;Guetschow, Michael;Doehner, Hartmut;Walther, Wolfgang;Keller, Ulrich;Bullinger, Lars;Mertins, Philipp;Kroenke, Jan. And the article was included in Nature Communications in 2022.Computed Properties of C24H29N7O2 This article mentions the following:

The immunomodulatory drugs (IMiDs) lenalidomide and pomalidomide are highly effective treatments for multiple myeloma. However, virtually all patients eventually relapse due to acquired drug resistance with resistance-causing genetic alterations being found only in a small subset of cases. To identify non-genetic mechanisms of drug resistance, we here perform integrated global quant. tandem mass tag (TMT)-based proteomic and phosphoproteomic analyses and RNA sequencing in five paired pre-treatment and relapse samples from multiple myeloma patients. These analyses reveal a CDK6-governed protein resistance signature that includes myeloma high-risk factors such as TRIP13 and RRM1. Overexpression of CDK6 in multiple myeloma cell lines reduces sensitivity to IMiDs while CDK6 inhibition by palbociclib or CDK6 degradation by proteolysis targeting chimeras (PROTACs) is highly synergistic with IMiDs in vitro and in vivo. This work identifies CDK6 upregulation as a druggable target in IMiD-resistant multiple myeloma and highlights the use of proteomic studies to uncover non-genetic resistance mechanisms in cancer. 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: 571190-30-2Computed Properties of C24H29N7O2).

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. 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.Computed Properties of C24H29N7O2

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

Assessment of cytochrome P450 3A4-mediated drug-drug interactions for ipatasertib using a fit-for-purpose physiologically based pharmacokinetic model was written by Jing, Jing;Chen, Yuan;Musib, Luna;Jin, Jin Y.;Cheung, Kit Wun Kathy;Yoshida, Kenta;Sane, Rucha. And the article was included in Cancer Chemotherapy and Pharmacology in 2022.Electric Literature of C24H29N7O2 This article mentions the following:

Ipatasertib, a potent and highly selective small-mol. inhibitor of AKT, is currently under investigation for treatment of cancer. Ipatasertib is a substrate and a time-dependent inhibitor of CYP3A4. It exhibits non-linear pharmacokinetics at subclin. doses in the clin. dose escalation study. To assess the DDI risk of ipatasertib at the intended clin. dose of 400 mg with CYP3A4 inhibitors, inducers, and substrates, a fit-for-purpose physiol. based pharmacokinetic (PBPK) model of ipatasertib was developed. The PBPK model was constructed in Simcyp using in silico, in vitro, and clin. data and was optimized and verified using clin. data. The PBPK model described non-linear pharmacokinetics of ipatasertib and captured the magnitude of the observed clin. DDIs. Following repeated doses of 400 mg ipatasertib once daily (QD), the PBPK model predicted a 3.3-fold increase of ipatasertib exposure with itraconazole; a 2-2.5-fold increase with moderate CYP3A4 inhibitors, erythromycin and diltiazem; and no change with a weak CYP3A4 inhibitor, fluvoxamine. Addnl., in the presence of strong or moderate CYP3A4 inducers, rifampicin and efavirenz, ipatasertib exposures were predicted to decrease by 86% and 74%, resp. As a perpetrator, the model predicted that ipatasertib (400 mg) caused a 1.7-fold increase in midazolam exposure. This study demonstrates the value of using a fit-for-purpose PBPK model to assess the clin. DDIs for ipatasertib and to provide dosing strategies for the concurrent use of other CYP3A4 perpetrators or victims. 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: 571190-30-2Electric Literature of C24H29N7O2).

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. Simple N-substituted piperazines have been found in many drug molecules. 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. Electric Literature of C24H29N7O2

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

Prognostic role of tumor subtype and germline BRCA mutation in advanced breast cancer patients treated with palbociclib plus endocrine therapy was written by Park, Song Yi;Suh, Koung Jin;Lee, Dae-Won;Ryu, Han Suk;Kim, Miso;Kim, Se Hyun;Lee, Kyung-Hun;Kim, Tae-Yong;Kim, Jee Hyun;Park, In Ae;Im, Seock-Ah. And the article was included in Breast Cancer Research and Treatment in 2022.Reference of 571190-30-2 This article mentions the following:

Abstract: Purpose: Palbociclib is a cyclin-dependent kinase 4 and 6 inhibitor which shows promising effect in hormone receptor-pos. breast cancer. The purpose of this study is to evaluate the real-world efficacy and toxicity of palbociclib plus endocrine therapy. Methods: This is a retrospective study performed in two tertiary referral hospitals in Korea. Advanced breast cancer patients who were treated with 1st-line palbociclib plus endocrine therapy were enrolled. Results: A total of 216 patients were included between August 2016 and May 2019. Median age was 56 (29-89) years old and 75 patients (34.7%) were premenopausal. Median progression-free survival (PFS) was 33.0 mo [95% confidence interval (CI) 24.7 to 41.3] and objective response rate was 59.3%. Luminal B patients had shorter PFS (33.0 mo vs. Not reached, p = 0.019) and tendency of lower ORR (58.3 vs. 62.0%, p = 0.19) compared to luminal A patients. Multivariate anal. revealed luminal B (adjusted hazard ratio 1.90, p = 0.038) and germline BRCA mutation (adjusted hazard ratio 5.57, p = 0.002) as an independent poor prognostic factor for PFS. The most common grade 3 or 4 adverse event was neutropenia (86.7%). Conclusion: The efficacy and toxicity of palbociclib in the real world were comparable to those of clin. trials. In addition, palbociclib with endocrine therapy was an effective treatment option for young patients. Luminal B and germline BRCA mutation were associated with inferior outcome. 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: 571190-30-2Reference of 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. Industrial applications of piperazine include the manufacture of plastics, resins, pesticides and brake fluids. 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.Reference of 571190-30-2

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

Presentation and management of diverse cutaneous reactions after cyclin-dependent kinase 4/6 inhibitor use was written by Amigo, Morgan;Hoffman, Kalyn;Chung, Catherine;Lustberg, Maryam;Wesolowski, Robert;VanDeusen, Jeffrey;Stover, Daniel;Suarez, Gabriel Tinoco;Cherian, Mathew;Kaffenberger, Benjamin;Dulmage, Brittany. And the article was included in Journal of the American Academy of Dermatology in 2022.Synthetic Route of C24H29N7O2 This article mentions the following:

It discusses on presentation and management of diverse cutaneous reactions after cyclin-dependent kinase 4/6 inhibitor use. Inpatient data from 2016-2020 was used to identify 9 patients with hormone receptor breast cancer and patient with liposarcoma who had received treatment with CDK 4/6i and experienced the development of cutaneous reactions. Palbociclib was the initial CDK4/6i used in 9 of the 10 cases and abemaciclib the initial agent in. The average time between drug initiation and the report of a cutaneous reaction was 6.8 mo, with a range of 21 days to 13 mo. The morphol. of the reactions included morbilliform eruptions with mucosal erosions, inflamed actinic keratoses (AKs), psoriasiform dermatitis with or without pustulosis, pustular dermatoses, and palmoplantar dermatitis. The agents used to treat these adverse cutaneous reactions represent commonly prescribed therapeutics in the field of dermatol., except for methylprednisolone, and have low adverse effect profiles. Understanding the potential morphol. and distribution of CDK4/6i-induced cutaneous reactions allows for faster recognition, accurate diagnosis, and appropriate therapeutic management to continue oncol. therapies, leading to more favorable outcomes. 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: 571190-30-2Synthetic Route of C24H29N7O2).

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. Intermediate for a wide range of pharmaceuticals, polymers, dyes, corrosion inhibitors, rubber accelerators and surfactants.Synthetic Route of C24H29N7O2

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

Starting dose selection of palbociclib in Chinese patients with breast cancer based on population kinetic-pharmacodynamic model of neutropenia was written by Jian, Weizhe;Xue, Junsheng;Yao, Qingyu;Chen, Rong;Yao, Ye;Wang, Mopei;Zhou, Tianyan. And the article was included in Cancer Chemotherapy and Pharmacology in 2022.Application In Synthesis of 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:

Abstract: Neutropenia is the most common adverse event (AE) of palbociclib, an oral CDK4/6 inhibitor for breast cancer. Neutropenia increases the risk of infection and is even life threatening. Asian patients generally suffer more severe neutropenia from palbociclib treatment, but the label does not recommend a reduction in the starting dose for Asian patients. Therefore, the study aimed to explore the exposure-response (E-R) relationship in Chinese patients and preliminarily generate a scale for starting dose selection of palbociclib in Chinese patients. After comparing the kinetic-pharmacodynamic (K-PD) and the pharmacokinetic/pharmacodynamic (PK/PD) model, a semi-mechanistic K-PD model was selected and developed on the basis of real-world data from 28 patients with breast cancer to describe the time course of longitudinal absolute neutrophil counts (ANC). The longitudinal ANC data were well described by the population K-PD model with reasonable parameters: mean transit time (MTT) of 198 h, feedback parameter (γ) of 0.317, baseline ANC level (Circ₀) of 3.36 x 10⁹ L^-1, drug effect coefficient (k_d) of 0.0349, and drug effect power (β) of 0.383. No covariate was included in the final model. The model showed that palbociclib dose-dependently reduced ANC levels in a Chinese population, and lower baseline ANC level was associated with more severe neutropenia. The dose selection scale suggested that palbociclib 125 mg daily was appropriate for Chinese patients with Circ₀ higher than 3.75 x 10⁹ L^-1. In summary, the K-PD model of palbociclib well described the longitudinal ANC in Chinese patients. Besides, the starting dose selection scale may provide reference for clinicians during individualized therapy. 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: 571190-30-2Application In Synthesis of 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. The piperazine scaffold is often found in biologically active compounds in different therapeutic areas. These therapeutic areas include antifungals, antidepressants, antivirals, and serotonin receptor (5-HT) antagonists/agonists. 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.Application In Synthesis of 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

AZD5153 reverses palbociclib resistance in ovarian cancer by inhibiting cell cycle-related proteins and the MAPK/PI3K-AKT pathway was written by Liu, Chen;Huang, Yuhan;Qin, Tianyu;You, Lixin;Lu, Funian;Hu, Dianxing;Xiao, Rourou;Qin, Xu;Guo, Ensong;Yang, Bin;Li, Xi;Fan, Junpeng;Li, Xiong;Fu, Yu;Liu, Si;Wang, Zhuozi;Dou, Yingyu;Wang, Wei;Li, Wenting;Yang, Xiaohang;Liu, Jingbo;Peng, Wenju;Zhang, Li;Cui, Yaoyuan;Sun, Chaoyang;Chen, Gang. And the article was included in Cancer Letters (New York, NY, United States) in 2022.Application of 571190-30-2 This article mentions the following:

The CDK4/6 inhibitor, palbociclib has recently entered clinic-trial stage for breast cancer treatment. However, translating its efficacy to other solid tumors has been challenging, especially for aggressive solid tumors. We found that the effect of palbociclib as a single agent was limited due to primary and acquired resistance in multiple ovarian cancer (OC) models. Among these, patient-derived organoid and xenograft models are two most representative models of drug responsiveness in patients with OC. In preclin. models, this study demonstrated that activated MAPK/PI3K-AKT pathway and cell cycle-related proteins induced the resistance to palbociclib, which was overcome by the addition of the bromodomain protein 4 (BRD4) inhibitor AZD5153. Moreover, this study revealed that AZD5153 and palbociclib had a synergistic lethal effect on inducing the cell cycle arrest and increasing apoptosis, even in RB-deficient cell lines. Based on these results, it is anticipated that this class of drugs, including AZD5153, which inhibit the cell cycle-related protein and MAPK/PI3K-AKT pathway, will exhibit synergistic effects with palbociclib in OC. 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: 571190-30-2Application of 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. A form in which piperazine is commonly available industrially is as the hexahydrate, C4H10N2. 6H2O, which melts at 44 °C and boils at 125–130 °C. 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).Application of 571190-30-2

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

RNA helicase DHX37 facilitates liver cancer progression by cooperating with PLRG1 to drive superenhancer-mediated transcription of cyclin D1 was written by Liu, Zhen;Ye, Youqiong;Liu, Yizhe;Liu, Yanfang;Chen, Huifang;Shen, Mengting;Wang, Zhen;Huang, Shenglin;Han, Leng;Chen, Zhiao;He, Xianghuo. And the article was included in Cancer Research in 2022.HPLC of Formula: 571190-30-2 This article mentions the following:

RNA helicases are dysregulated in tumors. Here, we identified DHX37 as one of the top RNA helicase genes with upregulated expression in hepatocellular carcinoma (HCC). DHX37 promoted proliferation of liver cancer cells in vitro and in vivo. Epigenomic profiling of DHX37-knockdown and control HCC cells revealed that DHX37 is associated with superenhancer activity. Mechanistically, DHX37 interacted with pleiotropic regulator 1 (PLRG1) to transcriptionally activate cyclin D1 (CCND1) expression via co-occupation of its promoter and superenhancer elements. DHX37 and PLRG1 promoted liver cancer cell proliferation and contributed to the poor prognosis of patients with HCC. Importantly, CCND1 inhibitors were effective as antiproliferative agents for liver cancer. These results together demonstrate a cooperative mechanistic interaction between DHX37 and PLRG1 that regulates CCND1 expression and promotes liver cancer progression, advancing our understanding of the epigenetic and transcriptional dysregulations mediated by RNA helicases and superenhancers in HCC. 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: 571190-30-2HPLC of Formula: 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 causes primary dermal irritation and skin burns at high concentrations. Piperazine also causes eye irritation in humans. 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. HPLC of Formula: 571190-30-2

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

Treatment patterns and clinical outcomes in patients with metastatic breast cancer treated with palbociclib-based therapies: real-world data in the Han population. was written by Mo, Hongnan;Ma, Fei;Li, Qing;Zhang, Pin;Yuan, Peng;Wang, Jiayu;Luo, Yang;Cai, Ruigang;Li, Qiao;Xu, Binghe. And the article was included in Chinese medical journal in 2022.Computed Properties of C24H29N7O2 This article mentions the following:

BACKGROUND: This study aimed to reveal the treatment patterns and clinical outcomes of diverse palbociclib-based regimens in Han patients with estrogen receptor-positive (ER+) metastatic breast cancer in routine clinical practice. METHODS: The clinical data of patients with ER+ metastatic breast cancer treated with palbociclib were collected from the National Cancer Center database. The efficacy profile of palbociclib in this Han population was evaluated, especially for various combination regimens. The efficacy of palbociclib-based therapy in patients with prior everolimus treatment was also assessed. RESULTS: A total of 186 patients from 89 cities in 18 provinces in China were enrolled. The median progression-free survival (PFS) was similar among different palbociclib-combined groups ( P  = 0.566): 10.0 months (95% confidence interval [CI] 3.8-16.1) in the +exemestane group, 9.7 months (95% CI 6.3-13.1) in the +letrozole group, 7.8 months (95% CI 5.5-10.2) in the +fulvestrant group, 7.2 months (95% CI 3.2-11.3) in the +toremifene group, and 6.1 months (95% CI 1.2-11.0) in the +anastrozole group. Thirty-four patients (18.3%) had received everolimus for their metastatic disease before the prescription of palbociclib. The disease control rate was significantly lower in patients who had received previous everolimus than in the everolimus-naïve group (50.0% vs . 82.2%, P  < 0.001). Patients pre-treated with everolimus had significantly worse PFS than those in the everolimus-naïve group (3.4 months vs . 8.8 months, P   =  0.001). After propensity score matching, patients pre-treated with everolimus had similar PFS (4.4 months, 95% CI 0.5-8.2) compared with everolimus-naïve patients (6.1 months, 95% CI 4.7-7.5, P   =  0.439). CONCLUSIONS: Various palbociclib-based regimens have promising efficacy in ER+ metastatic breast cancer in real-world settings, even in patients who had been pre-treated with everolimus. 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: 571190-30-2Computed Properties of C24H29N7O2).

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. Piperazines are very broad chemical group, covering a wide range of drugs from antidepressants to antihistamines. The connecting property of all these chemicals is the presence of a piperazine functional group.Computed Properties of C24H29N7O2

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