Momelotinib (CYT387)

Momelotinib (CYT387) is an ATP-competitive inhibitor of JAK1/JAK2 with IC50 of 11 nM/18 nM, ~10-fold selectivity versus JAK3. Phase 3.

Price Stock Quantity  
In DMSO USD 220 In stock
USD 170 In stock
USD 470 In stock
Bulk Inquiry

Massive Discount Available

Free Overnight Delivery on all orders over $ 500.

Momelotinib (CYT387) Chemical Structure

Momelotinib (CYT387) Chemical Structure
Molecular Weight: 414.46

Validation & Quality Control

Customer Reviews(2)

Quality Control & MSDS

Related Compound Libraries

JAK Inhibitors with Unique Features

Product Information

  • Compare JAK Inhibitors
    Compare JAK Products
  • Research Area

Product Description

Biological Activity

Description Momelotinib (CYT387) is an ATP-competitive inhibitor of JAK1/JAK2 with IC50 of 11 nM/18 nM, ~10-fold selectivity versus JAK3. Phase 3.
Targets JAK1 [1] JAK2 [1] JAK3 [1]
IC50 11 nM 18 nM 155 nM
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 2μ-4 μM. [1] A recent study shows that 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]
Features

Protocol(Only for Reference)

Kinase Assay: [1]

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.

Cell Assay: [1]

Cell lines Ba/F3, Ba/F3-JAK2V617F and Ba/F3-MPLW515L cells
Concentrations 0 to 10 μM
Incubation Time 72 hours
Method 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

Animal Study: [3]

Animal Models Balb/c mice are transplanted with bone marrow transduced with a JAK2V617F retrovirus.
Formulation CYT387 is dissolved in NMP (120 mg/mL final; 1-methyl-2-pyrrolidinone, Chromasolv Plus). 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
Dosages ≤50 mg/kg
Administration Administered via p.o.
Solubility 30% PEG400/0.5% Tween80/5% propylene glycol, , 30 mg/mL
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

Conversion of different model animals based on BSA (Value based on data from FDA Draft Guidelines)

SpeciesBaboonDogMonkeyRabbitGuinea pigRatHamsterMouse
Weight (kg)121031.80.40.150.080.02
Body Surface Area (m2)0.60.50.240.150.050.0250.020.007
Km factor202012128653
Animal A (mg/kg) = Animal B (mg/kg) multiplied by  Animal B Km
Animal A Km

For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.

Rat dose (mg/kg) = mouse dose (22.4 mg/kg) ×  mouse Km(3)  = 11.2 mg/kg
rat Km(6)
1

References

[1] Pardanani A, et al. Leukemia, 2009, 23(8), 1441-1445.

[2] Monaghan KA, et al. Leukemia, 2011, 25(12), 1891-1899.

view more

Clinical Trial Information( data from http://clinicaltrials.gov, updated on 2014-09-20)

NCT Number Recruitment Conditions Sponsor
/Collaborators
Start Date Phases
NCT01423058 Completed Primary Myelofibrosis|Post-Polycythemia Vera|Post-Essential Thrombocythemia Myelofibrosis Gilead Sciences August 2011 Phase 1|Phase 2
NCT00935987 Completed Primary Myelofibrosis|Post-Polycythemia Vera Myelofibrosis|Post-Essential Thrombocythemia Myelofibrosis Gilead Sciences November 2009 Phase 1|Phase 2

Chemical Information

Download Momelotinib (CYT387) SDF
Molecular Weight (MW) 414.46
Formula

C23H22N6O2

CAS No. 1056634-68-4
Storage 3 years -20℃Powder
6 months-80℃in DMSO
Synonyms LM-1149
Solubility (25°C) * In vitro DMSO 83 mg/mL (200 mM)
Water <1 mg/mL (<1 mM)
Ethanol <1 mg/mL (<1 mM)
In vivo 30% PEG400/0.5% Tween80/5% propylene glycol, 30 mg/mL
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.
Chemical Name N-(cyanomethyl)-4-(2-(4-morpholinophenylamino)pyrimidin-4-yl)benzamide

Research Area

Customer Reviews (2)


Click to enlarge
Rating
Source Blood, 2012, 120(19):4093-103. Momelotinib (CYT387) purchased from Selleck
Method Flow cytometric analysis
Cell Lines WT pan T cells
Concentrations 1 uM
Incubation Time
Results CYT387 dramatically reduced the expression of CXCR3 in activated WT T cells.

Click to enlarge
Rating
Source Dr. Claude Haan and Catherine Rolvering from University of Luxembourg. Momelotinib (CYT387) purchased from Selleck
Method Western blot
Cell Lines HEL cells
Concentrations 0-5 uM
Incubation Time 48 h
Results Cyt387 suppresses STAT5 phosphorylation only at concentrations above 1 uM, which is quite high compared to the other Jak inhibitors we have tested before, some of which have IC50‘s below 500 nM.

Product Citations (3)

Tech Support & FAQs

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Tel: +1-832-582-8158 Ext:3

If you have any other enquiries, please leave a message.

* Indicates a Required Field

Related JAK Products

  • Pacritinib (SB1518)

    Pacritinib (SB1518) is a potent and selective inhibitor of Janus Kinase 2 (JAK2) and Fms-Like Tyrosine Kinase-3 (FLT3) with IC50s of 23 and 22 nM, respectively. Phase 3.

  • XL019

    XL019 is a potent and selective JAK2 inhibitor with IC50 of 2.2 nM, exhibiting >50-fold selectivity over JAK1, JAK3 and TYK2. Phase 1.

    Features:High oral bioavailability in multiple species.

  • GLPG0634

    GLPG0634 is a selective JAK1 inhibitor with IC50 of 10 nM, 28 nM, 810 nM, and 116 nM for JAK1, JAK2, JAK3, and TYK2, respectively. Phase 2.

  • Ruxolitinib (INCB018424)

    INCB018424 is the first potent, selective, JAK1/2 inhibitor to enter the clinic with IC50 of 3.3 nM/2.8 nM, >130-fold selectivity for JAK1/2 versus JAK3.

  • Tofacitinib (CP-690550) Citrate

    Tofacitinib (CP-690550) Citrate is a novel inhibitor of JAK3 with IC50 of 1 nM, 20- to 100-fold less potent against JAK2 and JAK1.

  • Fedratinib (SAR302503, TG101348)

    TG-101348 (SAR302503) is a selective inhibitor of JAK2 with IC50 of 3 nM, 35- and 334-fold more selective for JAK2 versus JAK1 and JAK3. Phase 2.

  • AZD1480

    AZD1480 is a novel ATP-competitive JAK2 inhibitor with IC50 of 0.26 nM, selectivity against JAK3 and Tyk2, and to a smaller extent against JAK1. Phase 1.

  • Tofacitinib (CP-690550,Tasocitinib)

    Tofacitinib (CP-690550,Tasocitinib) is a novel inhibitor of JAK3 with IC50 of 1 nM, 20- to 100-fold less potent against JAK2 and JAK1.

  • WP1066

    WP1066 is a novel inhibitor of JAK2 and STAT3 with IC50 of 2.30 μM and 2.43 μM in HEL cells; shows activity to JAK2, STAT3, STAT5, and ERK1/2 not JAK1 and JAK3. Phase 1.

    Features:Similar to its parent compound AG490, WP1066 inhibits the phosphorylation of JAK2, but unlike AG490, WP1066 also degraded JAK2 protein.

  • Baricitinib (LY3009104, INCB028050)

    Baricitinib (LY3009104, INCB028050) is a selective JAK1 and JAK2 inhibitor with IC50 of 5.9 nM and 5.7 nM, ~70 and ~10-fold selective versus JAK3 and Tyk2, no inhibition to c-Met and Chk2. Phase 3.

Recently Viewed Items

Tags: buy Momelotinib (CYT387) | Momelotinib (CYT387) supplier | purchase Momelotinib (CYT387) | Momelotinib (CYT387) cost | Momelotinib (CYT387) manufacturer | order Momelotinib (CYT387) | Momelotinib (CYT387) distributor
Contact Us