Momelotinib (CYT387)

Name: Momelotinib (CYT387)
Brand: Selleck Chemicals
SKU: S2219
Rating: 5 (20 reviews)

For research use only. Not for use in humans.

Catalog No.S2219 Synonyms: LM-1149 , CYT11387

20 publications

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.

Selleck's Momelotinib (CYT387) has been cited by 20 publications

Cell Stem Cell, 2018, 23(2):252-265

PubMed: 30082068 ( click the link to review the publication )

EMBO Rep, 2019, 20(10):e47734

PubMed: 31448519 ( click the link to review the publication )

Cancer Res, 2019, 79(20):5382-5393

PubMed: 31405846 ( click the link to review the publication )

Int Immunopharmacol, 2019, 73:482-490

PubMed: 31173970 ( click the link to review the publication )

Oncol Rep, 2019, 41(3):1883-1892

PubMed: 30664175 ( click the link to review the publication )

PLoS One, 2019, 14(9):e0222944

PubMed: 31560729 ( click the link to review the publication )

Commun Biol, 2019, 2:156

PubMed: 31098401 ( click the link to review the publication )

Nat Commun, 2018, 9(1):2434

PubMed: 29934552 ( click the link to review the publication )

Transl Oncol, 2018, 11(4):971-978

PubMed: 29933129 ( click the link to review the publication )

Leukemia, 2018, 10.1038/s41375-018-0169-y

PubMed: 29884903 ( click the link to review the publication )

Blood, 2017, 130(12):1418-1429

PubMed: 28698206 ( click the link to review the publication )

Mol Cancer Ther, 2017, 16(10):2234-2245

PubMed: 28729401 ( click the link to review the publication )

Cancer Res, 2016, 76(18):5337-47

PubMed: 27440725 ( click the link to review the publication )

Sarcoma, 2016, 2016:3484673

PubMed: 27822137 ( click the link to review the publication )

Nat Cell Biol, 2015, 17(1):57-67

PubMed: 25487280 ( click the link to review the publication )

J Clin Invest, 2014, 124(12):5263-74

PubMed: 25384216 ( click the link to review the publication )

PLoS One, 2014, 9(11):e112014

PubMed: 25390891 ( click the link to review the publication )

Harvard University, 2014, Stegmaier K, et al.

PubMed: ( click the link to review the publication )

Cancer Lett, 2013, 341(2):224-30

PubMed: 23941832 ( click the link to review the publication )

Blood, 2012, 120(19):4093-103

PubMed: 22972985 ( click the link to review the publication )

Purity & Quality Control

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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	M1zGXnBzd2yrZnXyZZRqd25iYYPzZZk>	Mn\TO\|IhcA>?	NGq5U2FCdnSrcILvcIln\XKjdHn2[UBi[3Srdnn0fUBi\2GrboP0JIh2dWGwIGPFWFIh[2WubIOg[ZhxemW\|c3nu[{BLSUt{IG[2NVdHKG23dHHueEBscW6jc3WgZYZ1\XJiN{KgbJJ{KGK7IHHsZY1ieiCkbIXlJIF{e2G7LDDJR\|UxRTBwMkOyJO69VQ>?	NH;lbIIyQTd4MkKzPC=>
mouse BAF3 cells	MmDsVJJwdGmoZYLheIlwdiCjc4PhfS=>	NXfwbJNoPzJiaB?=	NVXFOFJ3SW62aYDyc4xq\mW{YYTpeoUh[WO2aY\peJkh[WejaX7zeEBud3W\|ZTDCRWY{KGOnbHzzJIV5eHKnc4PpcochXEWOLVrBT\|Ihc2mwYYPlJIFnfGW{IEeyJIhzeyCkeTDhcIFu[XJiYnz1[UBie3OjeR?=	NXLPUoFuOTl5NkKyN\|g>
human HEL 92.1.7 cells	NXzzV5U{WHKxbHnm[ZJifGmxbjDhd5NigQ>?	Mn3EO\|IhcA>?	MnzYRY51cXC{b3zp[oVz[XSrdnWgZYN1cX[rdImgZYdicW6\|dDDoeY1idiCKRVygPVIvOS55IHPlcIx{KGW6cILld5NqdmdiSlHLNkBXPjF5RjDteZRidnRia3nuZZNmKGGodHXyJFczKGi{czDifUBidGGvYYKgZox2\SCjc4PhfUwhUUN3ME2xMlgxPCEQvF2=	MnPGNVk4PjJ{M{i=

... Click to View More Cell Line Experimental Data

Assay

Methods	Test Index	PMID
Western blot	p-JAK2 / JAK2 / p-STAT3 / STAT3 ; PubMed: 26625308 Oncotarget RCC cell lines were treated for 24 hours with the indicated concentrations of CYT387, and lysates were probed with the indicated antibodies. Actin was used as loading control. p-Src / Src ; PubMed: 26625308 Oncotarget RCC cells were treated with 100 nM of dasatinib and 2 μM of CYT387, alone, in combination or DMSO for 24 hours and lysates were probed with the indicated antibodies.	26625308
Immunofluorescence	p62 / pS6 ; PubMed: 29138276 Genes Dev ACHN cells were grown on coverslips, treated with CYT387 for 24 h, and stained p62 and p-S6.	29138276
Growth inhibition assay	Cell viability; PubMed: 20385788 Blood Ba/F3-EpoR parental (cultured in media supplemented with 3 U/mL erythropoietin) or Ba/F3-EpoR-JAK2(V617F) cells (cultured in the absence of exogenous cytokines) were plated in 96-well plates over a dose gradient of CYT387 for 3 days at which point cell viability was measured with an MTS tetrazolium salt assay. Values represent mean ± SEM. n = 3; *P < .05.	20385788

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]	- Collapse 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]	- Collapse 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]	- Collapse 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
Smiles	O=C(NCC#N)C1=CC=C(C=C1)C2=NC(=NC=C2)NC3=CC=C(C=C3)N4CCOCC4

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Momelotinib (CYT387)