Momelotinib (CYT387)

Name: Momelotinib (CYT387)
Brand: Selleck Chemicals
SKU: S2219
Rating: 5 (26 reviews)

For research use only.

Catalog No.S2219 Synonyms: LM-1149 , CYT11387

26 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. Momelotinib (CYT387) induces apoptosis and autophagy. Phase 3.

Selleck's Momelotinib (CYT387) has been cited by 26 publications

Nat Med, 2020, 10.1038/s41591-020-0926-0

PubMed: 32572264 ( click the link to review the publication )

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

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

J Cancer, 2020, 6;11(13):3725-3735

PubMed: 32328177 ( click the link to review the publication )

Biochem Pharmacol, 2020, 114122

PubMed: 32592721 ( click the link to review the publication )

Apoptosis, 2020, 25(5-6):370-387

PubMed: 32394008 ( click the link to review the publication )

Transl Oncol, 2020, 13(2):481-489

PubMed: 32004866 ( click the link to review the publication )

Blood, 2019, 26;134(26):2388-2398

PubMed: 31697804 ( 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

Choose Selective JAK Inhibitors

Biological Activity

Description

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	NGTBRZpRem:uaX\ldoF1cW:wIHHzd4F6	NV:3R5ZqPzJiaB?=	MnHPRY51cXC{b3zp[oVz[XSrdnWgZYN1cX[rdImgZYdicW6\|dDDoeY1idiCVRWSyJINmdGy\|IHX4dJJme3OrbnegTmFMOiCYNkG3SkBufXSjboSgb4lv[XOnIHHmeIVzKDd{IHjyd{BjgSCjbHHtZZIh[my3ZTDhd5NigSxiSVO1NF0xNjJ\|MjFOwG0>	MUKxPVc3OjJ\|OB?=
mouse BAF3 cells	NIizNFZRem:uaX\ldoF1cW:wIHHzd4F6	NU\oU5pQPzJiaB?=	M1PPVGFvfGmycn;sbYZmemG2aY\lJIFkfGm4aYT5JIFo[Wmwc4SgcY92e2ViQlHGN{Bk\WyuczDlfJBz\XO\|aX7nJHRGVC2MQVuyJItqdmG\|ZTDh[pRmeiB5MjDodpMh[nliYXzhcYFzKGKudXWgZZN{[Xl?	NUDiUII1OTl5NkKyN\|g>
human HEL 92.1.7 cells	MXnQdo9tcW[ncnH0bY9vKGG\|c3H5	NGnsOnQ4OiCq	NV6ye3JwSW62aYDyc4xq\mW{YYTpeoUh[WO2aY\peJkh[WejaX7zeEBpfW2jbjDISWwhQTJwMT63JINmdGy\|IHX4dJJme3OrbnegTmFMOiCYNkG3SkBufXSjboSgb4lv[XOnIHHmeIVzKDd{IHjyd{BjgSCjbHHtZZIh[my3ZTDhd5NigSxiSVO1NF0yNjhyNDFOwG0>	NGL5[I4yQTd4MkKzPC=>

... 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. 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): 2% DMSO+40%PEG 300+ 3% Tween80 + ddH2O For best results, use promptly after mixing.	2mg/mlmg/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 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

In vivo Formulation Calculator (Clear solution)

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Method for preparing DMSO master liquid: ： mg drug pre-dissolved in μL DMSO (Master liquid concentration mg/mL， Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )

Method for preparing in vivo formulation：Take DMSO master liquid, next addμL PEG300， mix and clarify, next addμL Tween 80，mix and clarify, next add μL ddH₂O，mix and clarify.

Note：1.Please make sure the liquid is clear before adding the next solvent.
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The Serial Dilution Calculator Equation

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Tech Support

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.

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JAK Signaling Pathway Map

JAK Inhibitors with Unique Features

Selective JAK Inhibitor

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Most Potent JAK Inhibitor

AZD1480 : JAK2, IC50=0.26 nM.
FDA-approved JAK Inhibitor

Tofacitinib (CP-690550,Tasocitinib) : Approved by FDA for rheumatoid arthritis (RA).
Newest JAK Inhibitor

XL019 ^New : Potent and selective JAK2 inhibitor with IC50 of 2.2 nM, exhibiting >50-fold selectivity over JAK1, JAK3 and TYK2.

Related JAK Products

FLLL32 ^New

FLLL32 is a potent JAK2/STAT3 inhibitor with IC50 of <5 μM.
Cerdulatinib (PRT062070) ^New

Cerdulatinib (PRT-062070) is an oral active, multi-targeted tyrosine kinase inhibitor with IC50 of 12 nM/6 nM/8 nM/0.5 nM and 32 nM for JAK1/JAK2/JAK3/TYK2 and Syk, respectively. Also inhibits 19 other tested kinases with IC50 less than 200 nM.
Ruxolitinib (INCB018424)

Ruxolitinib (INCB018424) is the first potent, selective, JAK1/2 inhibitor to enter the clinic with IC50 of 3.3 nM/2.8 nM in cell-free assays, >130-fold selectivity for JAK1/2 versus JAK3. Ruxolitinib kills tumor cells through toxic mitophagy. Ruxolitinib induces autophagy and enhances apoptosis.
Tofacitinib (CP-690550) Citrate

Tofacitinib citrate (CP-690550 citrate) is a novel inhibitor of JAK with IC50 of 1 nM, 20 nM and 112 nM against JAK3, JAK2, and JAK1, respectively. Tofacitinib citrate has anti-infection activity.
Tofacitinib (CP-690550)

Tofacitinib (CP-690550,Tasocitinib) is a novel inhibitor of JAK3 with IC50 of 1 nM in cell-free assays, 20- to 100-fold less potent against JAK2 and JAK1. Tofacitinib inhibits the expression of antiapoptotic BCL-A1 and BCL-XL in human plasmacytoid dendritic cells (PDC) and induced PDC apoptosis.
AZD1480

AZD1480 is a novel ATP-competitive JAK2 inhibitor with IC50 of 0.26 nM in a cell-free assay, selectivity against JAK3 and Tyk2, and to a smaller extent against JAK1. Phase 1.
Fedratinib (TG101348)

Fedratinib (SAR302503, TG101348) is a selective inhibitor of JAK2 with IC50 of 3 nM in cell-free assays, 35- and 334-fold more selective for JAK2 versus JAK1 and JAK3. Fedratinib also inhibits FMS-like tyrosine kinase 3 (FLT3) and Ret with IC50 of 15 nM and 48 nM, respectively. Fedratinib has potential antineoplastic activity. Fedratinib inhibits proliferation and induces apoptosis. Phase 2.
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. WP1066 induces apoptosis. Phase 1.

Features:Similar to its parent compound AG490, WP1066 inhibits the phosphorylation of JAK2, but unlike AG490, WP1066 also degraded JAK2 protein.
Baricitinib (INCB028050)

Baricitinib (LY3009104, INCB028050) is a selective JAK1 and JAK2 inhibitor with IC50 of 5.9 nM and 5.7 nM in cell-free assays, ~70 and ~10-fold selective versus JAK3 and Tyk2, no inhibition to c-Met and Chk2. Baricitinib is found to reduce or interrupt the passage of the virus into target cells and is used in the treatment research for COVID-19. Phase 3.

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Momelotinib (CYT387)