description
Nilotinib Hydrochloride Monohydrate(923288-90-8) is the monohydrate monohydrochloride form of nilotinib, an orally bioavailable aminopyrimidine-derivative Bcr-Abl tyrosine kinase inhibitor with antineoplastic activity. Designed to overcome imatinib resistance resulting from Bcr-Abl kinase mutations, upon administration, nilotinib binds to and stabilizes the inactive conformation of the kinase domain of the Abl portion of the Bcr-Abl fusion protein, resulting in the inhibition of the constitutive kinase activity of Bcr-Abl protein. This inhibits the Bcr-Abl-mediated proliferation of Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia (CML) cells. Nilotinib also inhibits the receptor tyrosine kinases platelet-derived growth factor receptor (PDGF-R; PDGFR), mast/stem cell growth factor receptor Kit (c-Kit), and, to a lesser extent, colony-stimulating factor 1 receptor (CSF-1R; CSF1R), and discoidin domain-containing receptor 1 (DDR1).
Nilotinib Hydrochloride Monohydrate (Code C95229)
Clinical Use
Nilotinib hydrochloride monohydrate(923288-90-8) was approved by FDA in 2007 for the treatment of chronic and accelerated phase Ph chromosome-positive CML adult patients which have developed resistance or intolerance to prior therapy that included imatinib. In 2012, apart from these previous indications, nilotinib hydrochloride monohydrate has also been indicated for the treatment of newly diagnosed adult patients with Ph chromosome-positive CML in chronic phase.
Uses
Nilotinib Monohydrochloride Monohydrate might be useful in treatment of chronic myelogenous leukemia. It is a COVID19-related research product.
Chemical Properties
Nilotinib hydrochloride monohydrate (NHM) lacks a chiral center, making it incapable of tautomerism. NHM is a chemical compound with the following name: 4-methyl-N-[3-(4-methyl-1H-imidazol1-yl)-5-(trifuoromethyl) phenyl]-3-[(4-pyridin-3-ylpyrimidin-2-yl) amino] benzamide hydrochloride monohydrate. It is a white powder with a slight yellowish or greenish-yellowish shade. At 25 °C, the aqueous solubility of NHM markedly decreases with pH. Moreover, it is almost insoluble in bufer solutions with pH values higher than 4.5. NHM shows slight solubility in ethanol and methanol. Nilotinib Hydrochloride Monohydrate is the monohydrate monohydrochloride form of nilotinib, an orally bioavailable aminopyrimidine-derivative Bcr-Abl tyrosine kinase inhibitor with antineoplastic activity.
Uses
Nilotinib Monohydrochloride Monohydrate might be useful in treatment of chronic myelogenous leukemia. It is a COVID19-related research product.
Definition
Nilotinib, also known as AMN107, is a tyrosine kinase inhibitor under investigation as a possible treatment for chronic myelogenous leukemia (CML). A Phase I clinical trial in 2006 showed that this drug was relatively safe and offered significant therapeutic benefits in cases of CML which were found to be resistant to treatment with imatinib (Gleevec), another tyrosine kinase inhibitor used as a first-line treatment for CML.
Mechanism of action
Tasigna (nilotinib hydrochloride monohydrate) is an orally available signal transduction inhibitor of the Bcr-Abl kinase, c-kit and Platelet Derived Growth Factor (PDGF). Nilotinib binds to and stabilizes the inactive conformation of the kinase domain of Abl protein. In vitro, nilotinib inhibited Bcr-Abl mediated proliferation of murine leukemic cell lines and human cell lines derived from Ph+ CML patients. In vivo, nilotinib reduced the tumor size in a murine Bcr-Abl xenograft model.
Side effects
a headache, fatigue, gastrointestinal problems such as nausea, vomiting, diarrhea and constipation, muscle and joint pain, rash and other skin conditions, flu-like symptoms, and reduced blood cell count. Less typical side effects are those of the cardiovascular system, such as hypertension (high blood pressure), various types of arrhythmia, and prolonged QT interval. Interaction of nilotinib with OATP1B1 and OATP1B3 may alter its hepatic disposition and can lead to transporter mediated drug-drug interactions.
in vitro
In vitro, nilotinib inhibited Bcr-Abl mediated proliferation of murine leukemic cell lines and human cell lines derived from Ph+ CML patients. Under the conditions of the assays, nilotinib was able to overcome imatinib resistance resulting from Bcr-Abl kinase mutations, in 32 out of 33 mutations tested. In vivo, nilotinib reduced the tumor size in a murine Bcr-Abl xenograft model. Nilotinib inhibited the autophosphorylation of the following kinases at IC50 values as indicated: Bcr-Abl (20-60 nM), PDGFR (69 nM) and c-Kit (210 nM). Nilotinib is currently being trialed in people with Parkinson's disease, as it appears to be able to halt progression of the disease and even improve their symptoms.
