Momelotinib (CYT387)

Catalog No.S2219 Synonyms: LM-1149 , CYT11387

Molecular Weight(MW): 414.46

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

4 Customer Reviews

Shown are WT pan T cells (both CD4＋and CD8＋ T cells; CD4－T cells are CD8＋T cells) after drug treatment.

Blood 2012 120(19), 4093-103. Momelotinib (CYT387) purchased from Selleck.

IL-6- supported INA-6 cells were treated with the JAK inhibitors ruxolitinib (Rux; 10 nM) or CYT387 (CYT; 50 nM) for 1 hour and assessed for inhibition of STAT3 phosphorylation by immunoblotting.

J Clin Invest 2014 10.1172/JCI69094. Momelotinib (CYT387) purchased from Selleck.
Percent pJAK2 and pSTAT5 for each cell line and inhibitor condition are displayed relative to mean basal phosphoprotein levels of control CD45+14+18+ myeloid cells. Experiments were performed in triplicate. Statistical analyses were performed with ANOVA and the Dunnett post-test for multiple comparisons. *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001

Leukemia, 2018, doi:10.1038/s41375-018-0169-y. Momelotinib (CYT387) purchased from Selleck.

HEL cells, expressing the Jak2-V617F mutant and showing constitutive activation of STAT5, were treated for 3h with Cyt387 at the indicated concentrations. Cells lysates were then subjected to SDS-PAGE and Western blotting. The Blots were detected with the indicated fluorescent antibodies using the LI-COR Biosciences detection system.

2014 Dr. Claude Haan and Catherine Rolvering from University of Luxembourg. Momelotinib (CYT387) purchased from Selleck.

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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] (Cell-free assay)	JAK2 ^[1] (Cell-free assay)	JAK3 ^[1] (Cell-free assay)
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]

Cell Data

Cell Lines	Assay Type	Incubation Time	Activity Description	PMID
human SET2 cells	M1n1fHBzd2yrZnXyZZRqd25iYYPzZZk>	NFrTTIg4OiCq	M1H4dGFvfGmycn;sbYZmemG2aY\lJIFkfGm4aYT5JIFo[Wmwc4SgbJVu[W5iU1XUNkBk\WyuczDlfJBz\XO\|aX7nJGpCUzJiVk[xO2YhdXW2YX70JItqdmG\|ZTDh[pRmeiB5MjDodpMh[nliYXzhcYFzKGKudXWgZZN{[XluIFnDOVA:OC5{M{Kg{txO	NYPrZVdTOTl5NkKyN\|g>
mouse BAF3 cells	M33Mc3Bzd2yrZnXyZZRqd25iYYPzZZk>	MXi3NkBp	M2q4bWFvfGmycn;sbYZmemG2aY\lJIFkfGm4aYT5JIFo[Wmwc4SgcY92e2ViQlHGN{Bk\WyuczDlfJBz\XO\|aX7nJHRGVC2MQVuyJItqdmG\|ZTDh[pRmeiB5MjDodpMh[nliYXzhcYFzKGKudXWgZZN{[Xl?	NV;wdWZKOTl5NkKyN\|g>
human HEL 92.1.7 cells	NF;Y[YpRem:uaX\ldoF1cW:wIHHzd4F6	M3K1SFczKGh?	NXT5bVd1SW62aYDyc4xq\mW{YYTpeoUh[WO2aY\peJkh[WejaX7zeEBpfW2jbjDISWwhQTJwMT63JINmdGy\|IHX4dJJme3OrbnegTmFMOiCYNkG3SkBufXSjboSgb4lv[XOnIHHmeIVzKDd{IHjyd{BjgSCjbHHtZZIh[my3ZTDhd5NigSxiSVO1NF0yNjhyNDFOwG0>	NIHDe2wyQTd4MkKzPC=>

... Click to View More Cell Line Experimental Data

In vivo

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

Protocol

Kinase Assay:^[1]	+ Expand 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 Research:^[1]	+ Expand 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% CO_{2(Only for Reference)}
Animal Research:^[3]	+ Expand 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. (Only for Reference)

References

Solubility (25°C)

In vitro	DMSO	74 mg/mL (178.54 mM)
	Water	Insoluble
	Ethanol	Insoluble
In vivo	Add solvents to the product individually and in order(Data is from Selleck tests instead of citations): 30% PEG400+0.5% Tween80+5% propylene glycol For best results, use promptly after mixing.	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.

Chemical Information Download Momelotinib (CYT387) SDF

Molecular Weight	414.46
Formula	C₂₃H₂₂N₆O₂
CAS No.	1056634-68-4
Storage	3 years -20°C powder
Storage	2 years -80°C in solvent
Synonyms	LM-1149 , CYT11387

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Clinical Trial Information (data from https://clinicaltrials.gov, updated on 2018-11-16)

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

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JAK Signaling Pathway Map

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Tofacitinib (CP-690550,Tasocitinib)

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AZD1480

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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.

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Momelotinib (CYT387)