Sprycel

BACKGROUND: Dasatinib and other tyrosine kinase inhibitors (TKI) have revolutionized the treatment of chronic myeloid leukemia (CML). However, as a lipophilic weak base, crystalline monohydrate, dasatinib (Sprycel®) is poorly soluble, rendering a pH-dependent absorption and a highly variable bioavailability. Thus, co-medication with proton pump inhibitors (PPI) profoundly impairs dasatinib uptake and is clearly recommended against. XS004 is a novel oral immediate release and amorphous solid dispersion (ASD) formulation of dasatinib and is bioequivalent to the original crystalline dasatinib at 30% lower dosages...

BACKGROUND: Dasatinib (Sprycel®) is a tyrosine kinase inhibitor for treating chronic myeloid leukemia and Philadelphia chromosome-positive acute lymphoblastic leukemia. RESEARCH DESIGN & METHODS: We designed a phase I clinical study to demonstrate that the dasatinib tablet (YiNiShu®) (Chia Tai Tianqing Pharmaceutical Group Co., Ltd) and Dasatinib (Bristol Myers Squibb) were bioequivalent under fasting and fed conditions. The whole study was structured into the fasting trial and the postprandial trial...

Over half of new therapeutic approaches fail in clinical trials due to a lack of target validation. As such, the development of new methods to improve and accelerate the identification of cellular targets, broadly known as target ID, remains a fundamental goal in drug discovery. While advances in sequencing and mass spectrometry technologies have revolutionized drug target ID in recent decades, the corresponding chemical-based approaches have not changed in over 50 y. Consigned to outdated stoichiometric activation modes, modern target ID campaigns are regularly confounded by poor signal-to-noise resulting from limited receptor occupancy and low crosslinking yields, especially when targeting low abundance membrane proteins or multiple protein target engagement...

Cancer treatments such as chemotherapies may change or accelerate aging trajectories in cancer patients. Emerging evidence has shown that "omics" data can be used to study molecular changes of the aging process. Here, we integrated the drug-induced and normal aging transcriptomic data to computationally characterize the potential cancer drug-induced aging process in patients. Our analyses demonstrated that the aging-associated gene expression in the GTEx dataset can recapitulate the well-established aging hallmarks...

BACKGROUND: Cancer is spreading all over the world and it is becoming leading cause of major deaths. Today's most difficult task for every researcher is to invent a new drug that can treat cancer with minimal side effects. Many factors including pollution, modern lifestyle and food habits, exposure to oncogenic agents or radiations, enhanced industrialization etc. are causing cancer. Treatment of cancer is done by various methods that include chemotherapy, radiotherapy, surgery and immunotherapy in combination or singly along with kinase inhibitors...

The anticancer drug dasatinib (Sprycel) is a BCR-ABL1-targeted tyrosine kinase inhibitor used in treating chronic myelogenous leukemia that has been shown in clinical trials to display cardiovascular toxicities. While dasatinib potently inhibits BCR-ABL1, it is not a highly selective kinase inhibitor and may have off-target effects. A neonatal rat cardiac myocyte model was used to investigate potential mechanisms by which dasatinib damaged myocytes. The anthracycline cardioprotective drug dexrazoxane was shown to be ineffective in preventing dasatinib-induced myocyte damage...

BACKGROUND: All studies of treatment-free remission (TFR) in patients with chronic myeloid leukaemia have discontinued tyrosine kinase inhibitor (TKI) treatment abruptly and have focussed on patients with stable MR4 (BCR-ABL to ABL ratio ≤0·01%). We aimed to examine the effects of gradual treatment withdrawal and whether TFR is feasible for patients with less deep but stable remission. METHODS: The De-Escalation and Stopping Treatment with Imatinib, Nilotinib, or sprYcel (DESTINY) study is a non-randomised, phase 2 trial undertaken at 20 UK hospitals...

BACKGROUND: Dasatinib (Sprycel) was developed as a tyrosine kinase inhibitor targeting Bcr-Abl and the family of Src kinases. Dasatinib is commonly used for the treatment of acute lymphoblastic and chronic myelogenous leukemia. Previous clinical studies in melanoma returned inconclusive results and suggested that patients respond highly heterogeneously to dasatinib as single agent or in combination with standard-of-care chemotherapeutic dacarbazine. Reliable biomarkers to predict dasatinib responsiveness in melanoma have not yet been developed...

Dasatinib is a second-generation tyrosine kinase inhibitor (TKI) and it could be used as a second-line treatment for patients with chronic myeloid leukemia (CML). Yinishu, a generic dasatinib made in China, was approved by the China Food and Drug Administration in 2013 and it costs much less than the patented dasatinib SPRYCEL. The present study aimed to examine the efficacy and safety of Yinishu as a second-line treatment for CML by comparing the baseline clinical characteristics, rates of adverse events and efficacy between Yinishu and SPRYCEL groups...

Chronic myeloid leukemia (CML) is a rare hematopoietic stem cell disease that is typically characterized by the abnormal BCR-ABL1 fusion gene on the Philadelphia (Ph) chromosome in neoplastic cells. Dasatinib (Sprycel® ) is an orally administered, small molecule tyrosine kinase inhibitor indicated for the treatment of certain hematological malignancies, including Ph-positive CML in the chronic phase (Ph+ CML-CP) in adult and pediatric patients. In open-label phase 1 and phase 2 clinical trials, dasatinib produced early and durable target responses (i...

SPRYCEL® (Dasatinib) is a Biopharmaceutical Classification System II weakly basic drug that exhibits strong pH-dependent solubility. Dasatinib is currently presented in 2 drug product formulations as an adult immediate release tablet and a pediatric powder for oral suspension. A bioequivalence study comparing the formulations in adult healthy subjects found that overall exposure (AUC0-24 ) from suspension treatments was ∼9% to 13% lower, Cmax was similar, and median Tmax from powder for oral suspension was ∼30 min earlier...

Objective: To explore the incidence and severity of hepatic adverse events (AEs) and identify factors associated with hepatic AEs in patients with chronic myeloid leukemia (CML) in chronic phase (CP) treated with tyrosine kinase inhibitors (TKIs). Methods: Liver biochemistry parameters [including ALT(alanine aminotransferase), AST(aspartate aminotransferase), ALP(alkaline phosphatase), and TBil(total bilirubin)] during the first 6 months on imatinib (Gleevec(®)), dasatinib (Sprycel(®)) or nilotinib (Tasigna(®)) in CML-CP patients were collected and analyzed retrospectively...

OBJECTIVE: The aim of this study was to report cases of medication-related osteonecrosis of the jaws (MRONJ) associated with targeted therapy (TT) with or without concomitant antiresorptive treatment, among the Copenhagen ONJ cohort, which includes all consecutive cases of MRONJ seen in Copenhagen. STUDY DESIGN: We retrospectively studied the treatment of 204 consecutive patients with MRONJ, seen between January 2010 and May 2016, to identify those associated with TT...

Dasatinib (Sprycel® ) is an orally administered, small molecule inhibitor of multiple tyrosine kinases. In the phase 3 DASISION trial, dasatinib 100 mg once daily resulted in deeper and faster cytogenetic and molecular responses than imatinib 400 mg once daily in patients with newly diagnosed, chronic-phase chronic myeloid leukaemia (CML), although there was no significant between-group difference in progression-free survival (PFS) or overall survival (OS) in the longer term. In the phase 3 CA180-034 trial, a regimen of dasatinib 100 mg once daily provided the most favourable benefit-risk profile in patients with imatinib-resistant or -intolerant chronic-phase CML...

Dasatinib (Sprycel) is a tyrosine kinase inhibitor approved for treatment of chronic myeloid leukemia. In this study, we identify dasatinib as a potent inducer of Peroxisome proliferator-activated receptor gamma coactivator (PGC)-1α mRNA. Dasatinib increased PGC-1α mRNA expression up to 6-fold in 3T3-F442A adipocytes, primary adipocytes, and epididymal white adipose tissue from lean and diet-induced obese mice. Importantly, gene expression translated into increased PGC-1α protein content analyzed in melanoma cells and isolated mitochondria from adipocytes...

BACKGROUND: Experimental autoimmune encephalomyelitis (EAE) is a mouse model for multiple sclerosis (MS). EAE is mainly mediated by adaptive and innate immune responses that lead to an inflammatory demyelination and axonal damage. Dasatinib (Sprycel) is a selective protein tyrosine kinase inhibitor with immunomodulatory properties that abrogates multiple signal transduction pathways in immune cells. In the present research, our aim was to test the therapeutic efficacy of dasatinib in experimental model of MS...

Dasatinib (Sprycel®), a second-generation TKI, has been shown to be effective as an anticancer drug in the treatment of patients with chronic myeloid leukemia or Philadelphia chromosome-positive acute lymphoblastic leukemia who are resistant or intolerant to imatinib. Several methods of gefitinib synthesis are included in this review. UV spectroscopy of dasatinib showed a λmax of approximately 320-330nm, and IR spectroscopy principal peaks were observed at 3418 (NH), 3200 (OH), 1620 (CO), 1582 (CC and CN), 1513 (CHCH) cm(-1)...

The first treatment of chronic myeloid leukemia (CML) included spleen x-radiation and conventional drugs, mainly Busulfan and Hydroxyurea. This therapy improved the quality of life during the chronic phase of the disease, without preventing nor significantly delaying the progression towards advanced phases. The introduction of allogeneic stem cell transplantation (alloSCT) marked the first important breakthrough in the evolution of CML treatment, because about 50% of the eligible patients were cured. The second breakthrough was the introduction of human recombinant interferon-alfa, able to achieve a complete cytogenetic remission in 15% to 30% of patients, with a significant survival advantage over conventional chemotherapy...

BACKGROUND: Along with the increasing use and inauguration of novel antineoplastic substances (inhibitors, antibodies [Ab]) at various levels of the tumour cell-specific intracellular signalling (transduction cascade) on the cell surface and within the cell as well as messengers ["biologicals", "targeted therapy"]), a new quality, intensity and complexity of adverse effects was simultaneously developed, which have become more and more relevant even to oncosurgeons. AIM: A summary is given of clinically obtained expertise including recommendations for a competent approach, management and use of biologicals for targeted therapy in case of abnormal or adverse effects as well as toxic reactions, which are compared with available data from the literature and provided as systematic short review on the clinically used substances and drugs in GI tumour lesions...

Oral dasatinib (Sprycel(®)) is effective in the treatment of patients with newly diagnosed chronic-phase chronic myeloid leukemia (CML) or imatinib-resistant or imatinib-intolerant chronic-phase, accelerated-phase, or blast-phase CML. In particular, dasatinib is associated with better and faster responses than imatinib in patients with newly diagnosed chronic-phase CML. The response to dasatinib appears to be maintained in the longer-term. Dasatinib has an acceptable tolerability profile; it is associated with myelosuppression, with fluid retention being the most common nonhematologic adverse event...