| Identification | Back Directory | [Name]
Momelotinib | [CAS]
1056634-68-4 | [Synonyms]
CYT 387
LM-1149
CYT 11387
MoMelotinib
Orange solid
CYT387, >=98%
CYT 387(CYT 11387)
CYT387(momelotinib)
Momelotinib (CYT387)
momelotinib(JAK inhibitor)ORPHAN DRUG
N-(Cyanomethyl)-4-(2-((4-morpholinophenyl)-amino)pyrimidin-4-yl)benzamide
N-(cyanoMethyl)-4-(2-(4-Morpholin-4-ylphenylaMino)pyriMidin-4-yl)benzaMide
N-(Cyanomethyl)-4-[2-[[4-(4-morpholinyl)phenyl]amino]-4-pyrimidinyl]benzamide
Benzamide,N-(cyanomethyl)-4-[2-[[4-(4-morpholinyl)phenyl]amino]-4-pyrimidinyl]-
N-(Cyanomethyl)-4-[2-[[4-(4-morpholinyl)phenyl]amino]-4-pyrimidinyl]benzamide CYT 387 | [Molecular Formula]
C23H22N6O2 | [MDL Number]
MFCD16038899 | [MOL File]
1056634-68-4.mol | [Molecular Weight]
414.46 |
| Chemical Properties | Back Directory | [density ]
1.292 | [storage temp. ]
Store at -20°C | [solubility ]
insoluble in EtOH; insoluble in H2O; ≥20.7 mg/mL in DMSO | [form ]
Orange powder. | [pka]
10.94±0.46(Predicted) | [color ]
Light yellow to yellow | [CAS DataBase Reference]
1056634-68-4 |
| Questions And Answer | Back Directory | [Description]
Momelotinib (CYT387) is an ATP-competitive inhibitor of JAK1/JAK2 with IC50 of 11 nM/18 nM, ~10-fold selectivity versus JAK3. Phase 3. | [In vitro]
CYT387 inhibits the proliferation of parental Ba/F3 cells (Ba/F3-wt) stimulated by IL-3 with IC50 of 1400 nM. Furthermore, CYT387 also causes the inhibition of cell proliferation in cell lines constitutively activated by JAK2 or MPL signaling, including Ba/F3-MPLW515L cells, CHRF-288-11 cells and Ba/F3-TEL-JAK2 cells with IC50 of 200 nM, 1 nM and 700 nM, respectively. In addition, CYT387 has been shown to inhibit erythroid colony growth in vitro from JAK2V617F-positive PV patients with similar potency with IC50 of 2μ-4 μM. A recent study shows that CYT387 inhibits PI3K/AKT and Ras/MAPK signaling induced by IL-6 and IGF-1. Moreover, CYT387 induces apoptosis as a single agent and synergizes with the conventional anti-MM therapies bortezomib and melphalan in primary multiple myeloma (MM) cells. | [In vivo]
In a murine MPN model, CYT387 normalizes white cell counts, hematocrit, spleen size, and restores physiologic levels of inflammatory cytokines. |
| Hazard Information | Back Directory | [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. | [target]
JAK1 | [storage]
Store at -20°C |
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