Category: 380843-75-4

On July 31, 2020, Hino, Masayuki; Matsumura, Itaru; Fujisawa, Shin; Ishizawa, Kenichi; Ono, Takaaki; Sakaida, Emiko; Sekiguchi, Naohiro; Tanetsugu, Yusuke; Fukuhara, Kei; Ohkura, Masayuki; Koide, Yuichiro; Takahashi, Naoto published an article.Formula: C26H29Cl2N5O3 The title of the article was Phase 2 study of bosutinib in Japanese patients with newly diagnosed chronic phase chronic myeloid leukemia. And the article contained the following:

Abstract: This open-label, single-arm, phase 2 study (ClinicalTrials.gov, NCT03128411) evaluated the efficacy, safety, and pharmacokinetics of bosutinib at a starting dose of 400 mg once daily (QD) in Japanese patients with newly diagnosed chronic phase chronic myeloid leukemia (CP CML). The primary endpoint was major mol. response (MMR) at Month 12 in the modified as-treated population (Philadelphia chromosome-pos. [Ph+] patients with e13a2/e14a2 transcripts). Sixty Japanese patients with CP CML were treated with bosutinib; median age was 55 years (range 20-83), 60.0% were males, and all were Ph+ and had e13a2/e14a2 transcripts. After median follow-up of 16.6 mo (range 11.1-21.9), 41 (68.3%) patients remained on bosutinib. The MMR rate at Month 12 was 55.0% (2-sided 90% confidence interval: 44.4-65.6). There were no on-treatment transformations to accelerated/blast phase, and no patient died on treatment or within 28 days of the last bosutinib dose. The most common treatment-emergent adverse events were diarrhea (86.7%), increased alanine aminotransferase (55.0%), and increased aspartate aminotransferase (46.7%). The primary objective of this phase 2 study was met, and there were no new safety signals for bosutinib. These data suggest bosutinib is an effective first-line treatment option for Japanese patients with newly diagnosed CP CML. The experimental process involved the reaction of 4-((2,4-Dichloro-5-methoxyphenyl)amino)-6-methoxy-7-(3-(4-methylpiperazin-1-yl)propoxy)quinoline-3-carbonitrile(cas: 380843-75-4).Formula: C26H29Cl2N5O3

The Article related to bosutinib human phase chronic myeloid leukemia, bosutinib, chronic myeloid leukemia, japan, tyrosine kinase inhibitor, Pharmacology: Effects Of Neoplasm Inhibitors and Cytotoxic Agents and other aspects.Formula: C26H29Cl2N5O3

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Piperazines – an overview | ScienceDirect Topics

Chaekal, Ok-kyong; van Besien, Koen published an article in 2020, the title of the article was Allogeneic transplant for CML in chronic phase after failure of imatinib. Not needed or needlessly neglected?.COA of Formula: C26H29Cl2N5O3 And the article contains the following content:

Imatinib first reported in 2001 revolutionized treatment for CML and ushered in the “TKI era’. Second and third generation TKI’s soon followed and presented alternatives for patients failing or unable to tolerate imatinib. They compared them with 1361 patients reported to the Center for International Bone Marrow Transplant Research (CIBMTR) who underwent allogeneic transplantation, also after failing at least one TKI. All patients were diagnosed and treated between 2001 and 2013. About half of the patients had accelerated or blast phase disease. Nilotinib and dasatinib were FDA approved in the second half of 2007, Bosutinib and Ponatinib not until 2012. The most serious toxicities are cardiovascular with an increasing incidence of arterial and venous thrombosis. But numerous other side effects occur. For those who fail imatinib, complete cytogenetic remissions to second or third generation TKI are 50% at best. The experimental process involved the reaction of 4-((2,4-Dichloro-5-methoxyphenyl)amino)-6-methoxy-7-(3-(4-methylpiperazin-1-yl)propoxy)quinoline-3-carbonitrile(cas: 380843-75-4).COA of Formula: C26H29Cl2N5O3

The Article related to allogeneic transplant chronic myeloid leukemia imatinib tyrosine kinase inhibitor, Pharmacology: Effects Of Neoplasm Inhibitors and Cytotoxic Agents and other aspects.COA of Formula: C26H29Cl2N5O3

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Piperazines – an overview | ScienceDirect Topics

On April 30, 2022, Dahlen, Torsten; Edgren, Gustaf; Ljungman, Per; Flygt, Hjalmar; Richter, Johan; Olsson-Stromberg, Ulla; Wadenvik, Hans; Dreimane, Arta; Myhr-Eriksson, Kristina; Zhao, Jingcheng; Sjalander, Anders; Hoglund, Martin; Stenke, Leif published an article.Application of 380843-75-4 The title of the article was Adverse outcomes in chronic myeloid leukemia patients treated with tyrosine kinase inhibitors: Follow-up of patients diagnosed 2002-2017 in a complete coverage and nationwide agnostic register study. And the article contained the following:

Tyrosine kinase inhibitors (TKIs) have profoundly improved the clin. outcome for patients with chronic myeloid leukemia (CML), but their overall survival is still subnormal and the treatment is associated with adverse events. In a large cohort-study, we assessed the morbidity in 1328 Swedish CML chronic phase patients diagnosed 2002-2017 and treated with TKIs, as compared to that in carefully matched control individuals. Several Swedish patient registers with near-complete nationwide coverage were utilized for data acquisition. Median follow-up was 6 (IQR, 3-10) years with a total follow-up of 8510 person-years for the full cohort. Among 670 analyzed disease categories, the patient cohort showed a significantly increased risk in 142 while, strikingly, no category was more common in controls. Increased incidence rate ratios/IRR (95% CI) for more severe events among patients included acute myocardial infarction (AMI) 2.0 (1.5-2.6), heart failure 2.6 (2.2-3.2), pneumonia 2.8 (2.3-3.5), and unspecified sepsis 3.5 (2.6-4.7). When comparing patients on 2nd generation TKIs vs. imatinib in a within-cohort anal., nilotinib generated elevated IRRs for AMI (2.9; 1.5-5.6) and chronic ischemic heart disease (2.2; 1.2-3.9), dasatinib for pleural effusion (11.6; 7.6-17.7) and infectious complications, for example, acute upper respiratory infections (3.0; 1.4-6.0). Our extensive real-world data reveal significant risk increases of severe morbidity in TKI-treated CML patients, as compared to matched controls, particularly for 2nd generation TKIs. Whether this increased morbidity may also translate into increased mortality, thus preventing CML patients to achieve a normalized overall survival, needs to be further explored. The experimental process involved the reaction of 4-((2,4-Dichloro-5-methoxyphenyl)amino)-6-methoxy-7-(3-(4-methylpiperazin-1-yl)propoxy)quinoline-3-carbonitrile(cas: 380843-75-4).Application of 380843-75-4

The Article related to chronic myeloid leukemia imatinib nilotinib dasatinib bosutinib adverse events, Pharmacology: Effects Of Neoplasm Inhibitors and Cytotoxic Agents and other aspects.Application of 380843-75-4

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Piperazines – an overview | ScienceDirect Topics

On December 31, 2021, Abumiya, Maiko; Takahashi, Naoto; Takahashi, Saori; Yoshioka, Tomoko; Kameoka, Yoshihiro; Miura, Masatomo published an article.Category: piperazines The title of the article was Effects of SLC22A2 808G>T polymorphism and bosutinib concentrations on serum creatinine in patients with chronic myeloid leukemia receiving bosutinib therapy. And the article contained the following:

The purpose of this study was to investigate the effects of SLC22A2 808G>T polymorphism and trough concentrations (C0) of bosutinib on serum creatinine in 28 patients taking bosutinib. At 1, 3, 6, 12, 24, and 36 mo after administration, anal. of bosutinib C0 and creatinine was performed at the same time of day. Significant correlations were observed between bosutinib C0 and the change rate of serum creatinine or the estimated glomerular filtration rate (eGFR; r = 0.328, P < 0.001 and r = - 0.315, P < 0.001, resp.). These correlations were particularly high in patients having the SLC22A2 808G/G genotype (r = 0.345 and r = - 0.329, resp.); however, in patients having the 808T allele, there were no significant differences. In multivariate analyses, the SLC22A2 808G/G genotype, patient age, bosutinib C0 and second-line or later bosutinib were independent factors influencing the change rate of creatinine. Bosutinib elevated serum creatinine through organic cation transporter 2 (OCT2). We observed a 20% increase in serum creatinine with a median bosutinib C0 of 63.4-73.2 ng/mL. Periodic measurement of serum creatinine after bosutinib therapy is necessary to avoid progression to severe renal dysfunction from simple elevation of creatinine mediated by OCT2 following bosutinib treatment. The experimental process involved the reaction of 4-((2,4-Dichloro-5-methoxyphenyl)amino)-6-methoxy-7-(3-(4-methylpiperazin-1-yl)propoxy)quinoline-3-carbonitrile(cas: 380843-75-4).Category: piperazines

The Article related to polymorphism serum creatinine chronic myeloid leukemia bosutinib therapy human, Pharmacology: Effects Of Neoplasm Inhibitors and Cytotoxic Agents and other aspects.Category: piperazines

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Piperazines – an overview | ScienceDirect Topics

On August 1, 2021, Hall, Kevin H.; Brooks, Angelique; Waller, Edmund K. published an article.Recommanded Product: 380843-75-4 The title of the article was Overcoming TKI resistance in a patient with chronic myeloid leukemia using combination BCR-ABL inhibition with asciminib and bosutinib. And the article contained the following:

A case of 43-yr-old female was diagnosed with chronic myeloid leukemia in chronic phase (CML-CP) in 2001 when she presented with leukocytosis and a subsequent bone marrow biopsy confirmed the presence of BCR-ABL1 t(9;22) fusion oncogene is reported. As the patient had previously failed all other available TKIs, approval was obtained for use of asciminib through compassionate use. The patient stopped bosutinib and started asciminib 40 mg twice daily based on phase I single agent data in Apr. 2020. Unfortunately, her quant. BCR-ABL1 transcript continued to rise, and bosutinib 500 mg daily was resumed in addition to asciminib in August 2020 when her BCR-ABL1 transcript was 54.6%. Her transcript peaked 2 wk later at 95% but dramatically declined down to 0.1% within 3 mo of starting the combination. She has now continued combination therapy with bosutinib and asciminib for more than 8 mo to date with no discernable side effects. The experimental process involved the reaction of 4-((2,4-Dichloro-5-methoxyphenyl)amino)-6-methoxy-7-(3-(4-methylpiperazin-1-yl)propoxy)quinoline-3-carbonitrile(cas: 380843-75-4).Recommanded Product: 380843-75-4

The Article related to asciminib bosutinib anticancer combination bcr abl1 chronic myeloid leukemia, Pharmacology: Effects Of Neoplasm Inhibitors and Cytotoxic Agents and other aspects.Recommanded Product: 380843-75-4

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Piperazines – an overview | ScienceDirect Topics

On June 30, 2021, Is, Yusuf Serhat published an article.Reference of 4-((2,4-Dichloro-5-methoxyphenyl)amino)-6-methoxy-7-(3-(4-methylpiperazin-1-yl)propoxy)quinoline-3-carbonitrile The title of the article was Elucidation of Ligand/Protein Interactions between BCR-ABL Tyrosine Kinase and Some Commercial Anticancer Drugs Via DFT Methods. And the article contained the following:

In this study, the interactions of 7 com. available BCR-ABL tyrosine kinase enzyme inhibitors with amino acids in the active site of the relevant enzyme were investigated quantum mech. Here a per-residue study was carried out. Interaction energies were calculated by using the coordinates of the critical residues in the binding site of the enzyme and the drug mols. docked in this region. DFT methods were used during the QM processes. All interaction energies were calculated via M06-2X functional and 6-31G (d,p) basis set in vacuum. Based on the results obtained, it was tried to be determined which of the important residues in the binding cavity of the enzyme could better interact with the examined ligands. It is thought that this study may contribute to the development of tyrosine kinase enzyme inhibitors. The experimental process involved the reaction of 4-((2,4-Dichloro-5-methoxyphenyl)amino)-6-methoxy-7-(3-(4-methylpiperazin-1-yl)propoxy)quinoline-3-carbonitrile(cas: 380843-75-4).Reference of 4-((2,4-Dichloro-5-methoxyphenyl)amino)-6-methoxy-7-(3-(4-methylpiperazin-1-yl)propoxy)quinoline-3-carbonitrile

The Article related to tyrosine kinase anticancer drugs ligand protein interaction density function, Pharmacology: Effects Of Neoplasm Inhibitors and Cytotoxic Agents and other aspects.Reference of 4-((2,4-Dichloro-5-methoxyphenyl)amino)-6-methoxy-7-(3-(4-methylpiperazin-1-yl)propoxy)quinoline-3-carbonitrile

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

On July 31, 2022, Haddad, Fadi G.; Sasaki, Koji; Issa, Ghayas C.; Garcia-Manero, Guillermo; Ravandi, Farhad; Kadia, Tapan; Cortes, Jorge; Konopleva, Marina; Pemmaraju, Naveen; Alvarado, Yesid; Yilmaz, Musa; Borthakur, Gautam; DiNardo, Courtney; Jain, Nitin; Daver, Naval; Short, Nicholas J.; Jabbour, Elias; Kantarjian, Hagop published an article.SDS of cas: 380843-75-4 The title of the article was Treatment-free remission in patients with chronic myeloid leukemia following the discontinuation of tyrosine kinase inhibitors. And the article contained the following:

Tyrosine kinase inhibitors (TKIs) discontinuation in patients with Philadelphia-chromosome-pos. chronic myeloid leukemia (Ph-pos. CML) is increasingly considered. We aim to evaluate the outcome of patients with CML who discontinued TKIs, and determine the factors associated with differences in the success rates of treatment-free remission (TFR). Patients with Ph-pos. CML treated between Oct. 1999 and Feb. 2017 who discontinued therapy were analyzed. A major mol. response (MMR) was defined as BCR-ABL1/ABL1 ratio on the International Scale ≤0.1%. TFR failure was defined as the loss of MMR on any single test. We analyzed TFR rates according to duration and depth of response, and conducted a multivariate anal. for factors associated with loss of MMR. Two-hundred and eighty-four patients were analyzed; 199 patients (70%) electively discontinued TKIs. At a median follow-up of 36 mo (95% confidence interval, 32-40) after TKI discontinuation, 53 patients (19%) lost MMR. The estimated 5-yr TFR rate was 79%. All but one patient regained MMR after resuming therapy. The estimated 5-yr TFR rates were higher with MR4 and MR4.5 ≥5 years, compared with MR4 <5 years (87% vs. 92% vs. 64%; p < .0001). By multivariate anal., only the duration of MR4 or MR4.5 ≥5 years before stopping treatment was associated with a lower risk of loss of MMR. In summary, TFR is safe and feasible in patients with Ph-pos. CML on TKI therapy. Achieving MR4 or MR4.5 for at least 5 years is correlated with a better outcome. The experimental process involved the reaction of 4-((2,4-Dichloro-5-methoxyphenyl)amino)-6-methoxy-7-(3-(4-methylpiperazin-1-yl)propoxy)quinoline-3-carbonitrile(cas: 380843-75-4).SDS of cas: 380843-75-4

The Article related to chronic myeloid leukemia tyrosine kinase inhibitor treatment free remission, Pharmacology: Effects Of Neoplasm Inhibitors and Cytotoxic Agents and other aspects.SDS of cas: 380843-75-4

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Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics

On August 31, 2022, Gambacorti-Passerini, Carlo; Nicolini, Franck Emmanuel; Larson, Richard A.; Aroldi, Andrea; Fontana, Diletta; Piazza, Rocco; le Coutre, Philipp; Antolini, Laura; Assouline, Sarit published an article.Computed Properties of 380843-75-4 The title of the article was Caution in using second generation tyrosine kinase inhibitor, especially for first line therapy of chronic myeloid leukemia. And the article contained the following:

Rates of 142 nominal disease categories were significantly increased in CML patients vs. the general population, even after excluding the initial 6 mo of treatment, when factors associated with the presence of uncontrolled leukemia could be involved in generating the reported abnormalities. Based on these data our general policy for CML patients is to actively look for early diagnosis of second cancers. Whether this result derives from increased susceptibility, increased monitoring of patients or both,it remains to be established. This could be linked to the preferential inhibition of PDGFR over ABL1 operated by imatinib. A second important aspect of this paper relates to the use of second generation TKI (2GEN). This was particularly evident for nilotinib and dasatinib, for which sufficient data were available, while insufficient data were present regarding the use of bosutinib and ponatinib. Not surprisingly, Nilotinib resulted in an increased risk of cardiovascular events and diabetes development, while dasatinib use showed increased risks of pleural effusions and infections. Since CML patients may be taking these TKIs for many years, it is in cumbent on physicians to manage and minimize treatment-related risks and co-morbid conditions. In conclusion,the report is important issue in the management of CML: when a normal life expectancy is the goal of the therapy, the safety of the choosen TKI becomes of paramount importance, especially for first line therapy. The experimental process involved the reaction of 4-((2,4-Dichloro-5-methoxyphenyl)amino)-6-methoxy-7-(3-(4-methylpiperazin-1-yl)propoxy)quinoline-3-carbonitrile(cas: 380843-75-4).Computed Properties of 380843-75-4

The Article related to human chronic myeloid leukemia cardiovascular disease tki dasatinib safety, Pharmacology: Effects Of Neoplasm Inhibitors and Cytotoxic Agents and other aspects.Computed Properties of 380843-75-4

Referemce:
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Piperazines – an overview | ScienceDirect Topics

On July 31, 2022, Bruemmendorf, Tim H.; Cortes, Jorge E.; Milojkovic, Dragana; Gambacorti-Passerini, Carlo; Clark, Richard E.; le Coutre, Philipp; Garcia-Gutierrez, Valentin; Chuah, Charles; Kota, Vamsi; Lipton, Jeffrey H.; Rousselot, Philippe; Mauro, Michael J.; Hochhaus, Andreas; Hurtado Monroy, Rafael; Leip, Eric; Purcell, Simon; Yver, Anne; Viqueira, Andrea; Deininger, Michael W.; BFORE study investigators published an article.Reference of 4-((2,4-Dichloro-5-methoxyphenyl)amino)-6-methoxy-7-(3-(4-methylpiperazin-1-yl)propoxy)quinoline-3-carbonitrile The title of the article was Bosutinib versus imatinib for newly diagnosed chronic phase chronic myeloid leukemia: final results from the BFORE trial. And the article contained the following:

This anal. from the multicenter, open-label, phase 3 BFORE trial reports efficacy and safety of bosutinib in patients with newly diagnosed chronic phase (CP) chronic myeloid leukemia (CML) after five year’s follow-up. Patients were randomized to 400-mg once-daily bosutinib (n = 268) or imatinib (n = 268; three untreated). At study completion, 59.7% of bosutinib- and 58.1% of imatinib-treated patients remained on study treatment. Median duration of treatment and time on study was 55 mo in both groups. Cumulative major mol. response (MMR) rate by 5 years was higher with bosutinib vs. imatinib (73.9% vs. 64.6%; odds ratio, 1.57 [95% CI, 1.08-2.28]), as were cumulative MR4 (58.2% vs. 48.1%; 1.50 [1.07-2.12]) and MR4.5 (47.4% vs. 36.6%; 1.57 [1.11-2.22]) rates. Superior MR with bosutinib vs. imatinib was consistent across Sokal risk groups, with greatest benefit seen in patients with high risk. Treatment-emergent adverse events (TEAEs) were consistent with 12-mo data. After 5 years of follow-up there was an increase in the incidence of cardiac, effusion, renal, and vascular TEAEs in bosutinib- and imatinib-treated patients, but overall, no new safety signals were identified. These final results support 400-mg once-daily bosutinib as standard-of-care in patients with newly diagnosed CP CML. The experimental process involved the reaction of 4-((2,4-Dichloro-5-methoxyphenyl)amino)-6-methoxy-7-(3-(4-methylpiperazin-1-yl)propoxy)quinoline-3-carbonitrile(cas: 380843-75-4).Reference of 4-((2,4-Dichloro-5-methoxyphenyl)amino)-6-methoxy-7-(3-(4-methylpiperazin-1-yl)propoxy)quinoline-3-carbonitrile

The Article related to bosutinib imatinib diagnosed phase chronic myeloid leukemia clin trial, Pharmacology: Effects Of Neoplasm Inhibitors and Cytotoxic Agents and other aspects.Reference of 4-((2,4-Dichloro-5-methoxyphenyl)amino)-6-methoxy-7-(3-(4-methylpiperazin-1-yl)propoxy)quinoline-3-carbonitrile

Referemce:
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Ha, Y. N. E.; Dai, Y.; Wufuer, D.; Pidayi, M.; Anasihan, G.; Chen, L. published an article in 2020, the title of the article was Second-generation Src/Abl inhibitor bosutinib effectively induces apoptosis in human esophageal squamous cell carcinoma (ESCC) cells via inhibiting Src/Abl signaling.Computed Properties of 380843-75-4 And the article contains the following content:

Esophageal cancer is a prevalent type of cancer worldwide and is ranked sixth among cancer-associated mortalities. Aberrant activation of the non-receptor tyrosine kinase Src and c-Abl contribute to the progression of ESCC. Thus, targeting these kinases to treat ESCC is a promising strategy. In this paper, we report that the potent dual Src/Abl inhibitor bosutinib exerts anti-tumor effects on ESCC. Bosutinib inhibits ESCC cell proliferation in a dose-dependent manner. Furthermore, bosutinib suppresses the colony formation ability of ESCC cells. Mechanistically, bosutinib effectively inhibits c-Abl and Src and its downstream signaling pathways, PI3K/AKT/mTOR and JAK/STAT3. In addition, bosutinib enhances the cytotoxic effects of doxorubicin on ESCC cells. In summary, our results reveal that Src and Abl are potential therapeutic targets in ESCC and that the novel Src/Abl inhibitor bosutinib alone or in combination with other chemotherapeutic agents may be a viable option for treating ESCC patients. The experimental process involved the reaction of 4-((2,4-Dichloro-5-methoxyphenyl)amino)-6-methoxy-7-(3-(4-methylpiperazin-1-yl)propoxy)quinoline-3-carbonitrile(cas: 380843-75-4).Computed Properties of 380843-75-4

The Article related to src abl bosutinib human esophageal squamous cell carcinoma signaling, Pharmacology: Effects Of Neoplasm Inhibitors and Cytotoxic Agents and other aspects.Computed Properties of 380843-75-4

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