1. JAK/STAT Signaling
    Epigenetics
    Stem Cell/Wnt
    Autophagy
  2. JAK
    Autophagy

CYT387 (Synonyms: momelotinib)

Cat. No.: HY-10961 Purity: 98.02%
Data Sheet SDS Handling Instructions

CYT387 is an ATP-competitive inhibitor of JAK1/JAK2 with IC50 of 11 nM/18 nM, appr 10-fold selectivity versus JAK3.

For research use only. We do not sell to patients.
CYT387 Chemical Structure

CYT387 Chemical Structure

CAS No. : 1056634-68-4

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10 mM * 1 mL in DMSO $77 In-stock
5 mg $70 In-stock
10 mg $90 In-stock
50 mg $250 In-stock
100 mg $440 In-stock
200 mg $600 In-stock
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Other Forms of CYT387:

    CYT387 purchased from MCE. Usage Cited in: Leukemia. 2012 Oct;26(10):2233-44.

    Drug combination effect on phosphorylation of AKT. Expression of phospho-AKT and total AKT in MOLM13 cells treated for 15 minutes with DMSO vehicle, PKC412 (2.5 nM), Dasatinib (165 nM), or a combination of both. Protein lysates are prepared from MOLM13 cells, and are analyzed via immunoblotting with antibodies to phospho-AKT and total AKT.

    CYT387 purchased from MCE. Usage Cited in: Leukemia. 2012 Oct;26(10):2233-44.

    SCM stimulation of phospho-STAT5 and drug combination effect on phosphorylation of phospho-STAT5. Expression of phospho-STAT5 and total STAT5 in MOLM13 cells treated for 1.5 h with DMSO vehicle, PKC412 (5 nM), KIN40 (82.5 nM) or a combination of both. Results shown are representative of two independent experiments in which similar results are observed.
    • Biological Activity

    • Protocol

    • Technical Information

    • Purity & Documentation

    • References

    Description

    CYT387 is an ATP-competitive inhibitor of JAK1/JAK2 with IC50 of 11 nM/18 nM, appr 10-fold selectivity versus JAK3.

    IC50 & Target

    IC50: 11 nM (JAK1), 18 nM (JAK2)

    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 2 μM-4 μM[1]. 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[2].

    In Vivo

    In a murine MPN model, CYT387 normalizes white cell counts, hematocrit, spleen size, and restores physiologic levels of inflammatory cytokines[3].

    Clinical Trial
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    References
    Preparing Stock Solutions
    Concentration Volume Mass 1 mg 5 mg 10 mg
    1 mM 2.4128 mL 12.0639 mL 24.1278 mL
    5 mM 0.4826 mL 2.4128 mL 4.8256 mL
    10 mM 0.2413 mL 1.2064 mL 2.4128 mL
    Please refer to the solubility information to select the appropriate solvent.
    Kinase Assay
    [1]

    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. MCE has not independently confirmed the accuracy of these methods. They are for reference only.

    Cell Assay
    [1]

    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. MCE has not independently confirmed the accuracy of these methods. They are for reference only.

    Animal Administration
    [3]

    CYT387 is dissolved in NMP (120 mg/mL final; 1-methyl-2-pyrrolidinone).

    On day 32 after bone marrow transplantation (when all mice exhibit severe leukocytosis and erythrocytosis), mice are assigned to 3 groups such that each group had equivalent average body weight and blood counts. CYT387 is dissolved in NMP (120 mg/mL final; 1-methyl-2-pyrrolidinone). Subsequently, the CYT387/NMP mix is diluted with 0.14 M Captisol to a concentration of 6 mg/mL and further diluted with 0.1M Captisol to a final concentration of 4 mg/mL. All 3 groups of mice (n=12 per group) are administered CYT387 by oral gavage twice daily at 10- to 12-hour intervals from day 34 after bone marrow transplantation to day 82 (end of experiment). Mice receive NMP/Captisol without CYT387 (0 mg/kg group), 25 mg/kg CYT387, or 50 mg/kg CYT387. At day 82 after bone marrow transplantation, all mice are euthanized for analysis except for 2 mice each from the 50 mg/kg and 25 mg/kg groups, which are taken off CYT387 treatment and followed for 45 additional days. For assessment of the effects of CYT387 on normal blood counts, naive Balb/c mice are administered vehicle control, 50 mg/kg, or 100 mg/kg CYT387 in an identical fashion as described for the bone marrow transplant experimental mouse cohort. Peripheral blood is drawn at day 14, 28, 42, and 56 and levels of red cells, white cells, reticulocytes, granulocytes, lymphocytes, and monocytes are analyzed. MCE has not independently confirmed the accuracy of these methods. They are for reference only.

    References
    Molecular Weight

    414.46

    Formula

    C₂₃H₂₂N₆O₂

    CAS No.

    1056634-68-4

    Storage
    Powder -20°C 3 years
      4°C 2 years
    In solvent -80°C 6 months
      -20°C 1 month
    Shipping

    Room temperature in continental US; may vary elsewhere

    Solvent & Solubility

    DMSO: ≥ 40 mg/mL

    * "<1 mg/mL" means slightly soluble or insoluble. "≥" means soluble, but saturation unknown.

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    Inquiry Information

    Product Name:
    CYT387
    Cat. No.:
    HY-10961
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