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

CYT387 sulfate salt (Synonyms: momelotinib sulfate)

Cat. No.: HY-10962 Purity: >96.0%
Handling Instructions

CYT387 sulfate salt is an ATP-competitive inhibitor of JAK1/JAK2 with IC50 of 11 nM/18 nM, 10-fold selectivity versus JAK3 (IC50=155 nM).

For research use only. We do not sell to patients.

CYT387 sulfate salt Chemical Structure

CYT387 sulfate salt Chemical Structure

CAS No. : 1056636-06-6

Size Price Stock Quantity
10 mM * 1 mL in DMSO USD 129 In-stock
Stock in Sweden
Estimated Time of Arrival: December 31
5 mg USD 96 In-stock
Stock in Sweden
Estimated Time of Arrival: December 31
10 mg USD 126 In-stock
Stock in Sweden
Estimated Time of Arrival: December 31
50 mg USD 372 In-stock
Stock in Sweden
Estimated Time of Arrival: December 31
100 mg USD 642 In-stock
Stock in Sweden
Estimated Time of Arrival: December 31
200 mg   Get quote  
500 mg   Get quote  

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Other Forms of CYT387 sulfate salt:

    CYT387 sulfate salt 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 sulfate salt 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.

    View All JAK Isoform Specific Products:

    • Biological Activity

    • Protocol

    • Technical Information

    • Purity & Documentation

    • References

    Description

    CYT387 sulfate salt is an ATP-competitive inhibitor of JAK1/JAK2 with IC50 of 11 nM/18 nM, 10-fold selectivity versus JAK3 (IC50=155 nM).

    IC50 & Target[1]

    JAK1

    11 nM (IC50)

    JAK2

    18 nM (IC50)

    JAK3

    155 nM (IC50)

    In Vitro

    CYT387 sulfate salt inhibits growth of Ba/F3-JAK2V617F and human erythroleukemia (HEL) cells (IC50=1.5 μM) or Ba/F3-MPLW515L cells (IC50=200 nM), but has considerably less activity against BCR-ABL harboring K562 cells (IC50=58 μM) and FLT3 mutation harboring MV4-11 cells (IC50=3 μM). Proliferation of parental Ba/F3 cells (Ba/F3-wt) stimulated with IL-3 is inhibited with an IC50 value of 1.4 μM, consistent with the established role of IL-3-dependent signaling in the parental cell line[1].

    In Vivo

    CYT387 at twice the dose used in disease model (50 and 100 mg/kg) has little to no effect on peripheral blood counts over a period of 8 weeks. Median plasma peak concentrations are 7.1 μM with the lower dose and 32.1μM with the higher dose, with a half-life of approximately 2 hours. Trough levels at 12 hours are 10nM for the 25 mg/kg and 900nM for the 50 mg/kg dose. At day 34 after transplantation, the mean white blood cell counts and hematocrit values of the entire cohort exceeded the normal range for Balb/c mice by more than 1 SD. At this point, 6 mice are sacrificed and subjected to autopsy. In the remaining animals, treatment is initiated with 25 mg/kg CYT387, 50 mg/kg CYT387, or vehicle, administered twice daily by oral gavage (12 mice per treatment group). A rapid drop of the white cell counts is apparent in both dose cohorts as early as 6 days after initiation of treatment and a decline of the hematocrit is apparent after 20 days[2]. After oral dosing, CYT387 exhibits high plasma concentrations (Cmax= 40.4 μM; Tmax=4 h), with quantitative absolute oral bioavailability and an apparent half life of 2.4 h. The high oral bioavailability, can likely be partly ascribed to the low blood clearance of CYT387 (6.3 mL/min/kg) and therefore low susceptibility to hepatic first pass metabolism[3].

    Clinical Trial
    References
    Preparing Stock Solutions
    Concentration Volume Mass 1 mg 5 mg 10 mg
    1 mM 1.6377 mL 8.1884 mL 16.3768 mL
    5 mM 0.3275 mL 1.6377 mL 3.2754 mL
    10 mM 0.1638 mL 0.8188 mL 1.6377 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[1]. MCE has not independently confirmed the accuracy of these methods. They are for reference only.

    Cell Assay
    [1]

    CYT387 is dissolved in DMSO and subsequently diluted in culture medium for use[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. TheTEL/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 h at 37°C with 5% CO2[1]. MCE has not independently confirmed the accuracy of these methods. They are for reference only.

    Animal Administration
    [2]

    CYT387 is dissolved in NMP (120 mg/mL final; 1-methyl-2-pyrrolidinone, Chromasolv Plus) (Mice)[2].

    Mice[2]

    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 has equivalent average body weight and blood counts. CYT387 is dissolved in NMP (120 mg/mL final; 1-methyl-2-pyrrolidinone, Chromasolv Plus). Subsequently, the CYT387/NMP mix is diluted with 0.14M 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

    610.62

    Formula

    C₂₃H₂₆N₆O₁₀S₂

    CAS No.

    1056636-06-6

    SMILES

    O=C(NCC#N)C(C=C1)=CC=C1C2=NC(NC(C=C3)=CC=C3N4CCOCC4)=NC=C2.O=S(O)(O)=O.O=S(O)(O)=O

    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: ≥ 6.1 mg/mL

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

    Purity: >96.0%

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    Product Name:
    CYT387 sulfate salt
    Cat. No.:
    HY-10962
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