Momelotinib (CYT387)

Momelotinib (CYT387, LM-1149 , CYT11387) 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.

CAS No. 1056634-68-4

サイズ	価格(税別)	在庫状況
10mg	JPY 25500	国内在庫あり
50mg	JPY 70500	国内在庫あり
1g	JPY 220500	国内在庫あり

代表番号: 045-509-1970\|電子メール：[email protected] よく尋ねられる質問

文献中Selleckの製品使用例（47）

製品安全説明書

現在のバッチを見る：純度： 99.75%

99.75

Momelotinib (CYT387)関連製品

関連ターゲット	JAK1 JAK2 JAK3 Tyk2	もっと見る
関連化合物ライブラリー	Kinase Inhibitor Library FDA-approved Drug Library Natural Product Library Tyrosine Kinase Inhibitor Library JAK/STAT compound library	もっと見る

シグナル伝達経路

JAKシグナル伝達経路

JAK阻害剤の選択性比較

Cell Data

Cell Lines	Assay Type	Incubation Time	活性情報	PMID
CTLL-2	Antiproliferative assay	72 hrs	Antiproliferative activity against IL-2-stimulated mouse CTLL-2 cells expressing JAK1/JAK3 after 72 hrs by alamar blue assay, IC50=1.249μM.	19762238
BAF3	Antiproliferative assay	72 hrs	Antiproliferative activity against mouse BAF3 cells expressing TEL-JAK2 kinase after 72 hrs by alamar blue assay, IC50=0.798μM.	19762238
SET2	Antiproliferative assay	72 hrs	Antiproliferative activity against human SET2 cells expressing JAK2 V617F mutant kinase after 72 hrs by alamar blue assay, IC50=0.232μM.	19762238
BAF3	Antiproliferative assay	72 hrs	Antiproliferative activity against mouse BAF3 cells expressing wild type JAK2 kinase after 72 hrs by alamar blue assay in presence of IL-3, IC50=1.43μM.	19762238
HEL 92.1.7	Antiproliferative assay	72 hrs	Antiproliferative activity against human HEL 92.1.7 cells expressing JAK2 V617F mutant kinase after 72 hrs by alamar blue assay, IC50=1.804μM.	19762238
HEL	Antiproliferative assay	48 hrs	Antiproliferative activity against human HEL cells after 48 hrs by CCK-8 assay, IC50=2.3μM.	29940115
BAF3	Antiproliferative assay	72 hrs	Antiproliferative activity against mouse BAF3 cells expressing TEL-JAK3 kinase after 72 hrs by alamar blue assay, IC50=2.425μM.	19762238
K562	Antiproliferative assay	48 hrs	Antiproliferative activity against human K562 cells after 48 hrs by CCK-8 assay, IC50=6.5μM.	29940115
HL60	Antiproliferative assay	48 hrs	Antiproliferative activity against human HL60 cells after 48 hrs by CCK-8 assay, IC50=8.3μM.	29940115
DAOY	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for DAOY cells	29435139
SJ-GBM2	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SJ-GBM2 cells	29435139
A673	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for A673 cells	29435139
SK-N-MC	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SK-N-MC cells	29435139
BT-37	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for BT-37 cells	29435139
SK-N-SH	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SK-N-SH cells	29435139
BT-12	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for BT-12 cells	29435139
RD	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for RD cells	29435139
MG 63 (6-TG R)	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for MG 63 (6-TG R) cells	29435139
Rh41	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh41 cells	29435139
BAF3	Function assay		Inhibition of JAK2 V617F mutant in mouse BAF3 cells, IC50=1.5μM.	ChEMBL
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生物活性

製品説明

Momelotinib (CYT387, LM-1149 , CYT11387) 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.

Targets

JAK1 ^[1] (Cell-free assay)	JAK2 ^[1] (Cell-free assay)	JAK3 ^[1] (Cell-free assay)
11 nM	18 nM	155 nM

In Vitro
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]
Kinase Assay	Cell-free kinase activity assays
Kinase Assay	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.
細胞実験	細胞株	Ba/F3, Ba/F3-JAK2V617F and Ba/F3-MPLW515L cells
	濃度	0 to 10 μM
	反応時間	72 hours
	実験の流れ	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
実験結果図	Methods	Biomarkers	結果図	PMID
	Western blot	p-JAK2 / JAK2 / p-STAT3 / STAT3 p-Src / Src		26625308
	Immunofluorescence	p62 / pS6		29138276
	Growth inhibition assay	Cell viability		20385788

In Vivo
In Vivo	In a murine MPN model, CYT387 normalizes white cell counts, hematocrit, spleen size, and restores physiologic levels of inflammatory cytokines. ^[3]
動物実験	動物モデル	Balb/c mice are transplanted with bone marrow transduced with a JAK2V617F retrovirus.
	投与量	≤50 mg/kg
	投与経路	Administered via p.o.

NCT Number	Recruitment	Conditions	Sponsor/Collaborators	Start Date	Phases
臨床試験 (data from https://clinicaltrials.gov, updated on 2024-01-11)
NCT01236638	Completed	Primary Myelofibrosis\|Post-Polycythemia Vera Myelofibrosis\|Post-Essential Thrombocythemia Myelofibrosis	Sierra Oncology LLC - a GSK company	November 2010	Phase 2
NCT00935987	Completed	Primary Myelofibrosis\|Post-Polycythemia Vera Myelofibrosis\|Post-Essential Thrombocythemia Myelofibrosis	Sierra Oncology LLC - a GSK company	November 2009	Phase 1\|Phase 2

参考
[1] Pardanani A, et al. Leukemia, 2009, 23(8), 1441-1445. [2] Monaghan KA, et al. Leukemia, 2011, 25(12), 1891-1899. [3] Tyner JW, et al. Blood, 2010, 115(25), 5232-5240.

参考

化学情報

分子量	414.46	化学式	C₂₃H₂₂N₆O₂
CAS No.	1056634-68-4	SDF	Download Momelotinib (CYT387) SDFをダウンロードする
Smiles	C1COCCN1C2=CC=C(C=C2)NC3=NC=CC(=N3)C4=CC=C(C=C4)C(=O)NCC#N
保管	3 years -20°C(in the dark) powder	溶液の保管冷凍と解凍の繰り返しを避けるため小分けにしてください	1年-80°Cin solvent
保管	3 years -20°C(in the dark) powder	溶液の保管冷凍と解凍の繰り返しを避けるため小分けにしてください	1个月-20°Cin solvent

In vitro
Batch:

DMSO : 83 mg/mL ( (200.26 mM)；吸湿したDMSOは溶解度を減少させます。新しいDMSOをご使用ください。)

Water : Insoluble

Ethanol : Insoluble

モル濃度計算器

in vivo
Batch:

Add solvents to the product individually and in order.

投与溶液組成計算機

実験計算

モル濃度計算器

質量	濃度	体積	分子量
=	×	×

希釈計算器分子量計算器

投与溶液組成計算機(クリア溶液)

ステップ１：実験データを入力してください。（実験操作によるロスを考慮し、動物数を1匹分多くして計算・調製することを推奨します）

投与量 mg/kg 動物平均体重 g 投与体積（動物毎）μL 動物数匹

ステップ２：投与溶媒の組成を入力してください。（ロット毎に適した溶解組成が異なる場合があります。詳細については弊社までお問い合わせください）

% DMSO + % + % Tween 80 + % ddH₂O

%DMSO+ %

計算結果：

投与溶媒濃度： mg/ml;

DMSOストック溶液調製方法： mg 試薬を μL DMSOに溶解する（濃度 mg/mL, 注：濃度が当該ロットのDMSO溶解度を超える場合はご連絡ください。 )

投与溶媒調製方法：Take μL DMSOストック溶液に μL PEG300，を加え、完全溶解後μL Tween 80，を加えて完全溶解させた後 μL ddH₂O，を加え完全に溶解させます。

投与溶媒調製方法：μL DMSOストック溶液に μL Corn oil，を加え、完全溶解。

注意：１.ストック溶液に沈殿、混濁などがないことをご確認ください；
２.順番通りに溶剤を加えてください。次のステップに進む前に溶液に沈殿、混濁などがないことを確認してから加えてください。ボルテックス、ソニケーション、水浴加熱など物理的な方法で溶解を早めることは可能です。

C1=C0/X	C1:	LOG(C1):
C2=C1/X	C2:	LOG(C2):
C3=C2/X	C3:	LOG(C3):
C4=C3/X	C4:	LOG(C4):
C5=C4/X	C5:	LOG(C5):
C6=C5/X	C6:	LOG(C6):
C7=C6/X	C7:	LOG(C7):
C8=C7/X	C8:	LOG(C8):