Uses
Using ATP kinase assays, the IC50 values for CYT387 are a follows - JAK1 (11nM), JAK2, (18nM), JAK2 V617F (23nM) JAK3 (155nM), and TYK2 (17nM). In testing kinase arrays, CYT387 also had activity (defined as an IC50 < 100nM) detected against CDK2/cyclin A, MAPK8 (JNK1), PRKCN (PKD3), PRKD1 (PKCμ), ROCK2, and TBK1 kinase as well.
Definition
ChEBI: Momelotinib is a benzamide obtained by formal condensation of the carboxy group of 4-{2-[4-(morpholin-4-yl)anilino]pyrimidin-4-yl}benzoic acid with the primary amino group of aminoacetonitrile. It is an ATP-competitive JAK1/JAK2 inhibitor with IC50 of 11 nM and 18 nM, respectively. Used for the treatment of patients with intermediate- or high-risk myelofibrosis. It has a role as an EC 2.7.10.2 (non-specific protein-tyrosine kinase) inhibitor, an antineoplastic agent, an anti-anaemic agent and an apoptosis inducer. It is an aminopyrimidine, a member of morpholines, a secondary amino compound, a tertiary amino compound, a member of benzamides and a nitrile.
Biological Activity
cyt387, an aminopyrimidine derivative discovered by high-throughput enzyme and cell-based screening along with the optimization using structure-guided medicinal chemistry, is a potent and selective inhibitor of janus kinase 1 (jak1), janus kinase 2 (jak2) and tyrosine kinase 2 (tyk2) with values of 50% inhibition concentration ic50 of 11 nm, 18 nm, 155 nm and 17 nm respectively. recent studies have revealed that cyt387, at low nanomolar concentrations ranging between 500 and 1500 nm, is able to inhibit jak2 signaling pathway, suppress proliferation and induce apoptosis in jak2-dependent hematopoietic cell lines with non-hematopoietic cell lines intact.tyner jw, bumm tg, deininger j, wood l, aichberger kj, loriaux mm, druker bj, burns cj, fantino e, deininger mw. cyt387, a novel jak2 inhibitor, induces hematologic responses and normalizes inflammatory cytokines in murine myeloproliferative neoplasms. blood. 2010;115(25):5232-5240.
