| Name | Momelotinib |
| Description | Momelotinib (LM-1149) is an orally bioavailable small-molecule inhibitor of Janus kinases 1 and 2 (JAK1/2) with IC50 of 11 nM/18 nM. JAK1/2 inhibitor CYT387 competes with JAK1/2 for ATP binding, which may result in inhibition of JAK1/2 activation, inhibition of the JAK-STAT signaling pathway, and so the induction of apoptosis and a reduction of tumor cell proliferation in JAK1/2-expressing tumor cells. |
| Cell Research | Ba/F3 cells expressing JAK2V617F (Ba/F3-JAK2V617F) and MPLW515L (Ba/F3-MPLW515L) mutants, as well as CHRF-288-11 (JAK2T875N) and CMK (JAK3A572V) cells are used. The TEL/JAK2 and TEL/JAK3 fusions are generated and introduced into Ba/F3 murine cells. The TEL/JAK2- or TEL/JAK3-transfected cells are cultured in Dulbecco's modified Eagle's medium (DMEM) containing 10% fetal calf serum (FCS). Ba/F3 wild-type cells are cultured in RPMI containing 10% FCS supplemented with 5 ng/mL murine IL-3. Proliferation is measured using the Alamar Blue assay after incubating for 72 hours at 37 °C with 5% CO2 |
| Kinase Assay | Cell-free kinase activity assays: Glutathione-S-transferase (GST)-tagged JAK kinase domains expressed in insect cells are purified before use in a peptide substrate phosphorylation assay. Assays are carried out in 384-well optiplates using an Alphascreen Protein Tyrosine Kinase P100 detection kit and a PerkinElmer Fusion Alpha instrument. |
| In vitro | In a murine MPN model, CYT387 normalized blood cell density, white blood cell count and spleen size and restored physiological levels of inflammatory cytokines. |
| In vivo | In vitro, CYT387 inhibited IL-3-stimulated proliferation of parental Ba/F3 cells (IC50: 1400 nM). In addition, CYT387 inhibited the growth of red lineage colonies in JAK2V617F-positive PV patients in vitro with similar effect (IC50: 2-4 μM).CYT387 inhibited IGF-1- and IL-6-induced Ras/MAPK and PI3K/AKT signaling. In primary multiple myeloma cells, CYT387 alone or in combination with the MM therapeutic agents bortezomib and melphalan induced apoptosis.CYT387 was 9-fold more selective for JAK1 and JAK2 (IC50: 11 nM and 18 nM) than the JAK3 kinase (IC50: 155 nM).CYT387 also acted on cell lines with constitutive activation of JAK2 or MPL signaling. or MPL signaling cell lines, including Ba/F3-MPLW515L cells (IC50: 200 nM), CHRF-288-11 cells (IC50: 1 nM) and Ba/F3-TEL-JAK2 cells (IC50: 700 nM), and also inhibited cell proliferation. |
| Storage | Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice. |
| Solubility Information | Ethanol : < 1 mg/mL (insoluble or slightly soluble)
DMSO : 69 mg/mL (166.5 mM)
H2O : < 1 mg/mL (insoluble or slightly soluble)
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| Keywords | inhibit | JAK | Janus kinase | CYT 11387 | Inhibitor | CYT-387 | CYT-11387 | Autophagy | Apoptosis | LM 1149 | Momelotinib | CYT 387 | LM1149 |
| Inhibitors Related | Stavudine | 5-Fluorouracil | Sodium 4-phenylbutyrate | L-Ascorbic acid | Hydroxychloroquine | Guanidine hydrochloride | Taurine | Tributyrin | Curcumin | Paeonol | Naringin | Gefitinib |
| Related Compound Libraries | Bioactive Compound Library | Tyrosine Kinase Inhibitor Library | Kinase Inhibitor Library | Anti-Cancer Clinical Compound Library | Drug Repurposing Compound Library | Inhibitor Library | Anti-Aging Compound Library | Bioactive Compounds Library Max | Anti-Cancer Active Compound Library | Anti-Cancer Drug Library |
United States
