CYT387

JAK1/JAK2 & TBK1/IKK-ε inhibitor

CYT387, also known as Momelotinib, is a potent ATP-competitive inhibitor of Janus kinases JAK1 and JAK2 [1], thereby interrupting the signaling via the JAK‑STAT (signal transducers and activators of transcription) pathway. CYT387 is significantly less active against other kinases, including JAK3.

In addition, CYT387 is a potent inhibitor of the noncanonical IκB kinases IKK-ε and TANK-binding kinase 1 (TBK1) [2].

As a result, CYT387 prevents both NF-κB and STAT activation.

Consequently, this multi‑target inhibitor disrupts the expression of pro‑tumorigenic cytokines, induces apoptosis and suppresses proliferation of many cells types, in particular cells harboring the JAK2V617F mutation which is associated with blood cancers [1, 3, 4].

References:

1. Pardanani A. et al., 2009. CYT387, a selective JAK1/JAK2 inhibitor: In vitro assessment of kinase selectivity and preclinical studies using cell lines and primary cells from polycythemia vera patients. Leukemia 23:1441–5.
2. Zhu Z. et al., 2014. Inhibition of KRAS-driven tumorigenicity by interruption of an autocrine cytokine circuit. Cancer Discov. 4:452-65.
3. Tyner JW. et al., 2010. CYT387, a novel JAK2 inhibitor, induces hematologic responses and normalizes inflammatory cytokines in murine myeloproliferative neoplasms. Blood. 15:5232-40.
4. Monaghan KA. et al., 2011. The novel JAK inhibitor CYT387 suppresses multiple signalling pathways, prevents proliferation and induces apoptosis in phenotypically diverse myeloma cells. Leukemia. 25:1891-9.

Figures

Effect of CYT387 on HEK-Blue™ IFN-α/β cell response to type I and type III IFNs: HEK‑Blue™ IFN-α/β cells were incubated with 3 U/ml hIFN-α2b (grey), 1 U/ml hIFN-β1 (purple) or 10 ng/ml hIL-29 (hIFN-λ1) (red) and increasing concentrations of CYT387. After 24h incubation, IFN-induced ISG activation was assessed by measuring SEAP levels in the supernatant using QUANTI‑Blue™. Percentages of maximal response (no inhibitor) for each cytokine are shown.

Specifications

CAS number: 1056634-68-4

Formula: C₂₃H₂₂N₆O₂

Molecular weight: 414.5

Solubility: 70 mg/ml (168.9 mM) in DMSO

Quality control:

• Purity ≥97% (UHPLC)
• The absence of bacterial contamination (e.g. lipoproteins and endotoxins) is confirmed using HEK-Blue™ TLR2 and HEK-Blue™ TLR4 cells.
• The inhibitory activity of CYT387 has been assessed using cellular assays.

Contents

• 10 mg CYT387

CYT387 is shipped at room temperature.

Store at -20 °C.