Momelotinib

SKU: orb1307329

Description

Momelotinib (CYT387) is a potent and orally bioavailable JAK1/2 inhibitor (IC50: 11 nM/18 nM) that blocks ATP binding, disrupting JAK-STAT signaling. This action leads to inhibited proliferation and induced apoptosis in relevant tumor cells, as demonstrated in cellular and animal models of myeloproliferative neoplasms.

Research Area

Cardiovascular Research, Cell Biology, Epigenetics & Chromatin, Signal Transduction, Stem Cell & Developmental Biology

Key Properties

• CAS Number: 1056634-68-4
• MW: 414.46
• Purity: 98.75%
• Formula: C₂₃H₂₂N₆O₂
• SMILES: O=C(NCC#N)c1ccc(cc1)-c1ccnc(Nc2ccc(cc2)N2CCOCC2)n1
• Target: Autophagy,JAK,Apoptosis
• Solubility: DMSO:62.5 mg/mL (150.8 mM);10% DMSO+40% PEG300+5% Tween 80+45% Saline:1 mg/mL (2.41 mM);Ethanol:< 1 mg/mL (insoluble or slightly soluble);H2O:< 1 mg/mL (insoluble or slightly soluble)

Bioactivity

• Target IC50:
  JAK3:155 nM|JAK1:11 nM|JAK2:18 nM
• 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.
• 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.
• 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

Storage & Handling

• Storage: store at low temperature | Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice/Shipping at ambient temperature.
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

Momelotinib, JAK3, Janus kinase, JAK1, JAK2, JAK, inhibit, LM 1149, LM1149, LM-1149, Inhibitor, Apoptosis, Autophagy, CYT 11387, CYT 387, CYT387, CYT-387, CYT11387, CYT-11387

Compound Identifiers

PubChem CID

25062766