In the evolving field of cancer therapy, Dasatinib monohydrate has carved out its niche. This drug, with its potent and specific characteristics, has become a key weapon against various malignant tumors. Despite containing a single water molecule in its chemical structure, its therapeutic impact is profound. Let's delve into the unique properties and applications of Dasatinib monohydrate, exploring its role in targeted cancer therapy.
As an inhibitor of tyrosine kinases, Dasatinib inhibits multiple variants of this kinase, commonly used in treating chronic myeloid leukemia and Philadelphia chromosome-positive acute lymphoblastic leukemia. It is an effective oral formulation with broad market prospects. Dasatinib tablets marketed in China include Bristol-Myers Squibb's Sprycel and CTTQ's Iclusig. According to literature reports, Dasatinib has known crystal forms such as monohydrate (MH H1-7), anhydrous form (AH N-6), unstable anhydrous form (T1H1-7), and various solvent compounds. Among them, MH H1-7 and AH N-6 exhibit good physical stability, making them ideal candidates for drug development.
Dasatinib monohydrate, a hydrate form, is a hydrate of Dasatinib. It is used in the treatment of chronic, accelerated, or blast phase chronic myeloid leukemia. Note that the name "Dasatinib" is used to refer to both the monohydrate (USAN) and anhydrous Dasatinib (INN). It acts as an antineoplastic and tyrosine kinase inhibitor, containing Dasatinib (anhydrous).
Dasatinib monohydrate combats cancer cells by targeting specific pathways vital for cancer cell growth and survival. Acting as an effective tyrosine kinase inhibitor, it disrupts crucial cellular signaling processes. These tyrosine kinases act like molecular switches, promoting uncontrolled cell proliferation when aberrantly activated, a hallmark of cancer. Dasatinib can bind to several key tyrosine kinases and inhibit their activity, most notably Bcr-Abl protein found in many cases of chronic myeloid leukemia (CML). By blocking Bcr-Abl and other tyrosine kinases, Dasatinib disrupts the signaling cascades within cancer cells, including halting cell division, triggering apoptotic pathways (cell death), and impeding the ability of cancer cells to migrate and invade healthy tissues.
Dasatinib is an oral multi-kinase inhibitor used in the treatment of Philadelphia chromosome (Ph)-positive leukemia. Ph is a chromosomal abnormality found in patients with chronic myeloid leukemia (CML) and acute lymphoblastic leukemia (ALL), where the ABL tyrosine kinase and breakpoint cluster region (BCR) gene transcribe a fused protein BCR-ABL. BCR-ABL is associated with uncontrolled ABL tyrosine kinase activity and is involved in the pathogenesis of CML and 15-30% of ALL cases. Dasatinib also inhibits a range of kinases associated with cancer, including several Src family kinases.
Unlike Imatinib, another tyrosine kinase inhibitor used to treat CML and Ph-positive ALL, Dasatinib inhibits both active and inactive conformations of the ABL kinase domain. Furthermore, mutations in the BCR-ABL kinase domain may lead to relapse during Imatinib therapy. Since Dasatinib does not interact with some residues involved in these mutations, its use represents a treatment option for cancer patients who have developed resistance to Imatinib. Dasatinib's use was first approved by the FDA in 2006.
Yes, Dasatinib monohydrate and Dasatinib are essentially the same drug. Here are the specific classifications: (1) Dasatinib: This refers to the active drug molecule itself. (2) Dasatinib monohydrate: This is a crystal form of Dasatinib, comprising one water molecule bound to each molecule of Dasatinib.
How much water is in dasatinib monohydrate? Dasatinib monohydrate contains a certain proportion of water. The weight of water molecules in the total molecular weight of Dasatinib monohydrate is fixed (18.02 g/mol), approximately 3.5% of the total weight.
In the Biopharmaceutics Classification System (BCS), Dasatinib monohydrate is generally classified as class II. This means it has high permeability, facilitating absorption, but low solubility. This solubility characteristic poses challenges for formulation, as it can limit the rate of dissolution and absorption of the drug into the bloodstream, ultimately affecting its bioavailability.
To overcome this barrier and optimize the drug delivery of Dasatinib monohydrate, pharmaceutical scientists explore various formulation strategies. These strategies may include reducing particle size to increase surface area for improved dissolution, utilizing the amorphous form of the drug to enhance solubility, or complexing the drug with specific excipients to enhance its water solubility. By employing these approaches, the aim of formulations is to create Dasatinib monohydrate preparations with higher bioavailability, leading to more consistent and effective therapeutic outcomes.
The molecular weight of Dasatinib monohydrate is a key aspect of its drug properties. We can determine its weight by adding up the atomic masses of the atoms composing it. In this case, the dasatinib monohydrate molecular weight is approximately 506.02 g/mol. The logS of Dasatinib monohydrate is -4.6, refractive index: 133.08 m3·mol-1, boiling point: >223°C. This drug is a hydrate of Dasatinib, formed by combining Dasatinib (hydrochloride) (CAS number: 863127-77-9) with a water molecule. Characteristics of this drug include: (1) a relatively high melting point, approximately 97-99°C; (2) a high density of 1408g/cm3. What is the solubility of dasatinib monohydrate? Dasatinib monohydrate is soluble in DMSO and methanol, but requires mild sonication. Its water solubility is poor and may degrade.
Understanding these properties is crucial for drug design and development. For example, the drug's molecular weight affects its ability to passively traverse cell membranes, thereby influencing its potential efficacy. By carefully considering these physicochemical properties, scientists can optimize drug design, creating medications with better absorption, distribution, and ultimately therapeutic effects.
Dasatinib monohydrate is typically available in tablet form, with various doses to meet individual needs and treatment goals. The appropriate dosage regimen is determined by several factors, including the specific type and stage of cancer being treated, the patient's
overall health, and their response to the medication. For example, treatment for chronic myeloid leukemia may involve different doses compared to treating Philadelphia chromosome-positive acute lymphoblastic leukemia. Dasatinib monohydrate is generally taken orally, with or without food. However, certain foods and medications can affect its absorption, so following the doctor's instructions regarding timing and potential interactions is crucial. To enhance compliance, patients should take Dasatinib monohydrate at a consistent time each day and develop a habit of remembering their medication. If any side effects or difficulty swallowing tablets arise, consulting healthcare professionals for alternative options is important.
Using Dasatinib monohydrate therapy to treat chronic myeloid leukemia (CML) and certain types of acute lymphoblastic leukemia (ALL) may come with some side effects. These may include nausea, vomiting, diarrhea, fatigue, weakness, skin issues, and skeletal problems. Risk assessment and management strategies can help doctors determine if patients are suitable for such treatment and devise tailored treatment plans for them.
During treatment, close monitoring of patients by doctors is necessary to ensure their safety. This includes regular blood tests, electrocardiograms, imaging studies, etc., to ensure the patient's well-being and promptly detect and address any adverse reactions. Meanwhile, patients should follow the doctor's advice, maintain clean and moisturized skin, intake adequate calcium and vitamin D, undergo regular bone density checks, and engage in moderate physical activity.
Throughout the treatment process, doctors also need to devise appropriate monitoring plans based on the patient's specific circumstances. For example, patients at risk of pleural effusion need more frequent thoracic examinations to ensure their safety. For patients at risk of lung infections, more frequent lung examinations are required. For patients at risk of bone marrow suppression, more frequent blood tests are needed to ensure their bone marrow function is normal.
For many cancer patients, Dasatinib monohydrate has become a beacon of hope. Its targeted interference with cancer cell growth pathways provides a valuable tool for treating chronic myeloid leukemia and other malignant tumors. With further research into its potential applications, Dasatinib holds promise for broader therapeutic use. By advocating for continued research and initiatives to improve affordability and accessibility, we can strive to make this potent weapon against cancer a reality for more patients.
[1] https://www.fda.gov/media/148472/download#
[2] Wang Jianming, Chen Yanmei, Zhang Hailu, et al. Crystal analysis of Dasatinib raw materials [J]. Journal of China Pharmaceutical University, 2015, 46(05): 575-578.
[3] https://pubchem.ncbi.nlm.nih.gov/compound/Dasatinib-hydrate
[4] https://go.drugbank.com/salts/DBSALT001849
[5] https://www.ema.europa.eu/en/documents/scientific-discussion/sprycel-epar-scientific-discussion_en.pdf
[6] https://www.apexbt.com/dasatinib-monohydrate.html
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