クロラムブシル

A: Chlorambucil is a bifunctional alkylating agent that primarily targets DNA within cells. [] It covalently binds to DNA, forming interstrand and intrastrand crosslinks, which disrupts DNA replication and transcription, ultimately leading to cell death. [, , , , ] This process is particularly effective in rapidly dividing cells, explaining its efficacy against certain cancers.

A: Research suggests that chlorambucil, in combination with ibrutinib, can influence the AKT signaling pathway in mantle cell lymphoma cells. This combination leads to upregulation of caspase-3 and downregulation of BCL-2, PI3K, and p-AKT/AKT, promoting apoptosis. []

A: While chlorambucil primarily targets DNA, certain analogues show moderate specificity for AT base pairs in the minor groove of DNA. []

A: Chlorambucil (IUPAC name: 4-[4-[bis(2-chloroethyl)amino]phenyl]butanoic acid) has the molecular formula C14H19Cl2NO2 and a molecular weight of 304.22 g/mol. [, ]

ANone: The provided research focuses mainly on chlorambucil's application as a pharmaceutical compound. Therefore, information about its compatibility with various materials or its stability outside of biological contexts and formulations is limited within these studies.

ANone: The research primarily focuses on chlorambucil's role as a chemotherapeutic agent. No catalytic properties or alternative applications are discussed within these papers.

A: While the provided research does not delve into detailed computational studies, one paper mentions the use of quantitative structure-activity relationship (QSAR) models to understand the relationship between the structure of chlorambucil analogues and their DNA binding affinity. []

A: Studies on amidine analogues of chlorambucil, where the chlorambucil moiety is linked to a 5-[4-(N-alkylamidino)phenyl]-2-furancarboxamide group, demonstrated enhanced cytotoxicity against human breast cancer MCF-7 cells compared to chlorambucil alone. This increased activity correlated with stronger DNA-binding affinity and topoisomerase II inhibition. []

A: Yes, researchers have developed chlorambucil-taurocholate, a conjugate that utilizes bile acid transporters (specifically NTCP) overexpressed in hepatocellular carcinomas to deliver the drug more selectively. [] This approach aims to enhance drug accumulation within tumor cells while potentially reducing off-target effects.

A: Researchers are exploring nanoformulations to improve chlorambucil's stability and delivery. One study encapsulated chlorambucil in a long-circulating nanoemulsion modified with poly(ethylene glycol) (PEG). [] This formulation demonstrated improved pharmacokinetic parameters, including higher AUC and longer half-life, compared to a non-PEGylated nanoemulsion and chlorambucil solution.

A: A study developed self-assembled micelles using an amphiphilic chlorambucil prodrug, CLB-HDH, where chlorambucil is conjugated to 1,6-hexanediamine hydrochloride. [] These micelles demonstrated enhanced cellular internalization and improved therapeutic activity both in vitro and in vivo compared to free chlorambucil, suggesting a promising drug delivery strategy.

A: Yes, researchers have developed photoresponsive fluorescent organic nanoconjugates using squaric acid and a coumarin-chlorambucil conjugate (Sq-Cou-Cbl). [] Upon visible light irradiation, these nanoconjugates release chlorambucil in a controlled manner and generate a photoproduct with PDT activity. This dual-action system allows for self-monitored combination therapy with enhanced anticancer activity.

ANone: The research papers primarily focus on the therapeutic aspects and clinical applications of chlorambucil. Information regarding specific SHE regulations or risk minimization strategies is not included within these studies.

A: Oral bioavailability of chlorambucil can be variable and decrease with repeated treatment cycles. [] One study found that dose-corrected AUC for the first 2 hours decreased by 33% after five cycles compared to the first cycle. [] This suggests potential for accelerated metabolism and/or reduced oral bioavailability with repeated dosing.

A: One study investigating the combination of chlorambucil and fludarabine in chronic lymphocytic leukemia patients found that concomitant administration of chlorambucil limited the dose intensity of fludarabine that could be tolerated. [] This suggests potential pharmacokinetic interactions that require careful dose adjustments in combination therapy.

A: Yes, numerous studies explored chlorambucil in combination therapies. For example: * Chlorambucil + Rituximab: This combination showed superior event-free survival compared to chlorambucil alone in patients with extranodal marginal-zone B-cell lymphoma [] and MALT lymphoma. [] * Chlorambucil + Fludarabine: This combination was studied in relapsed chronic lymphocytic leukemia, but the study revealed dose-limiting toxicity. [] * Chlorambucil + Ibrutinib: This combination demonstrated a synergistic effect in inducing apoptosis in mantle cell lymphoma cell lines. []

A: One study utilized a subcutaneous colon-38 adenocarcinoma tumor mouse model and found that chlorambucil delivered in a long-circulating nanoemulsion significantly enhanced therapeutic efficacy compared to a non-PEGylated nanoemulsion and chlorambucil solution. []

A: Research suggests that the presence of p53 and ATM gene abnormalities significantly affects the sensitivity of CLL cells to these drugs. [] CLL samples with p53 abnormalities were predominantly resistant to fludarabine, while those with ATM deletions showed increased sensitivity compared to wild-type cells. []

A: Yes, studies show that the monoclonal antibody rituximab can sensitize CLL cells to both fludarabine and chlorambucil in vitro. [, ] This sensitization effect was observed regardless of p53 or ATM gene status, highlighting rituximab's potential in overcoming resistance mechanisms. []

A: While this Q&A avoids detailing side effects, it's important to acknowledge that research mentions chlorambucil's association with myelosuppression, particularly leukopenia. [, ] Additionally, one study raised concerns about the potential long-term risk of cutaneous and hematological malignancies, particularly myeloid leukemia, with prolonged chlorambucil use in rheumatoid arthritis patients. []

A: Beyond nanoemulsions and micelles, researchers are investigating the use of tumor-specific antibodies to deliver chlorambucil directly to cancer cells. One study demonstrated that chlorambucil bound to an anti-tumor antibody could be internalized by EL4 lymphoma cells via endocytosis after forming "caps" on the cell surface. [] This targeted approach aims to increase drug concentration at the tumor site and potentially minimize systemic toxicity.

A: While the research doesn't pinpoint specific biomarkers for predicting chlorambucil's efficacy, it highlights the importance of genetic and molecular factors. One study found that Binet stage C and advanced Rai stages (3 and 4) correlated with statistically significant lower progression-free survival in CLL patients treated with chlorambucil and rituximab. [] This suggests that disease stage and other prognostic indicators could play a role in treatment response.

A: High-performance liquid chromatography (HPLC) is commonly employed to measure chlorambucil and its active metabolite, phenylacetic acid mustard, in biological samples. [] This method enables researchers to analyze drug concentrations and pharmacokinetic parameters.