Pacritinib

別名：SB1518

製品コード：S8057 純度：99.94%

Pacritinib 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 in cell-free assays, respectively. Phase 3.

CAS No. 937272-79-2

サイズ	価格(税別)	在庫状況
10mM (1mL in DMSO)	JPY 67300	国内在庫あり
5mg	JPY 44500	国内在庫あり
50mg	JPY 145500	国内在庫あり
1g	JPY 748500	国内在庫なし(納期7~10日)

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（18）

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製品安全説明書

現在のバッチを見る：純度： 99.94%

99.94

Pacritinibと併用されることが多い化合物

Pracinostat (SB939)

Pacritinib and Pracinostat completely abrogate the JAK2-autophosphorylation and enhance cell death in Set-2 cells.

Novotny-Diermayr V, et al. Blood Cancer J. 2012 May;2(5):e69.

Pacritinib関連製品

関連ターゲット	JAK1 JAK2 JAK3 Tyk2	もっと見る
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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	Concentration	Incubation Time	活性情報	PMID
KMS-12-BM	Function assay	2 uM	3 hrs	Inhibition of JAK2 in IL-6-stimulated human KMS-12-BM cells assessed as suppression of STAT3 phosphorylation at TY705 residue at 2 uM pretreated for 3 hrs followed by IL-6 stimulation by immunoblot method	27541357
MOLM14	Function assay	0.1 uM	3 hrs	Inhibition of JAK2 in IL-6-stimulated human MOLM14 cells assessed as suppression of STAT3 phosphorylation at TY705 residue at 0.1 uM pretreated for 3 hrs followed by IL-6 stimulation by immunoblot method	27541357
TAMH	Cytotoxicity assay		24 hrs	Cytotoxicity against TAMH cells assessed as cell viability after 24 hrs by CellTiter-Glo assay, IC50 = 3.68 μM.	28953386
AC10	Cytotoxicity assay		24 hrs	Cytotoxicity against human AC10 cells assessed as cell viability after 24 hrs by CellTiter-Glo assay, IC50 = 2.02 μM.	28953386
NKYS	Antiproliferative assay		48 hrs	Antiproliferative activity against human NKYS cells after 48 hrs by CellTiter-Glo luminescent assay, IC50 = 1.6 μM.	28953386
KG1	Antiproliferative assay		48 hrs	Antiproliferative activity against human KG1 cells after 48 hrs by CellTiter-Glo luminescent assay, IC50 = 1.48 μM.	28953386
KHYG	Antiproliferative assay		48 hrs	Antiproliferative activity against human KHYG cells after 48 hrs by CellTiter-Glo luminescent assay, IC50 = 1.24 μM.	28953386
OPM2	Antiproliferative assay		48 hrs	Antiproliferative activity against human OPM2 cells after 48 hrs by CellTiter-Glo luminescent assay, IC50 = 1.21 μM.	28953386
HEL 92.1.7	Antiproliferative assay		36 hrs	Antiproliferative activity against human HEL 92.1.7 cells after 36 hrs by PrestoBlue dye based assay, IC50 = 1.17 μM.	28953386
KMS-12-BM	Antiproliferative assay		48 hrs	Antiproliferative activity against human KMS-12-BM cells after 48 hrs by CellTiter-Glo luminescent assay, IC50 = 0.75 μM.	28953386
MOLM14	Antiproliferative assay		48 hrs	Antiproliferative activity against human MOLM14 cells after 48 hrs by CellTiter-Glo luminescent assay, IC50 = 0.079 μM.	28953386
TAMH	Antiproliferative assay		24 hrs	Antiproliferative activity against mouse TAMH cells after 24 hrs by CellTiter-Glo assay, IC50 = 3.68 μM.	27541357
PC3	Antiproliferative assay		72 hrs	Antiproliferative activity against human PC3 cells after 72 hrs by MTT assay, IC50 = 2.41 μM.	27541357
MDA-MB-231	Antiproliferative assay		72 hrs	Antiproliferative activity against human MDA-MB-231 cells after 72 hrs by MTT assay, IC50 = 2.43 μM.	27541357
HEL 92.1.7	Antiproliferative assay		48 hrs	Antiproliferative activity against HEL 92.1.7 cells harboring JAK2 V617F mutant after 48 hrs by CellTiter-Glo assay, IC50 = 1.726 μM.	27541357
HCT116	Antiproliferative assay		48 hrs	Antiproliferative activity against human HCT116 cells after 48 hrs by CellTiter-Glo assay, IC50 = 1.69 μM.	27541357
NKYS	Antiproliferative assay		48 hrs	Antiproliferative activity against human NKYS cells after 48 hrs by CellTiter-Glo assay, IC50 = 1.6 μM.	27541357
KG1	Antiproliferative assay		48 hrs	Antiproliferative activity against human KG1 cells after 48 hrs by CellTiter-Glo assay, IC50 = 1.48 μM.	27541357
KHYG	Antiproliferative assay		48 hrs	Antiproliferative activity against human KHYG cells after 48 hrs by CellTiter-Glo assay, IC50 = 1.24 μM.	27541357
OPM2	Antiproliferative assay		48 hrs	Antiproliferative activity against human OPM2 cells after 48 hrs by CellTiter-Glo assay, IC50 = 1.21 μM.	27541357
HEL 92.1.7	Antiproliferative assay		36 hrs	Antiproliferative activity against HEL 92.1.7 cells harboring JAK2 V617F mutant after 36 hrs by PrestoBlue dye based assay, IC50 = 1.17 μM.	27541357
HCT116	Antiproliferative assay		72 hrs	Antiproliferative activity against human HCT116 cells after 72 hrs by MTT assay, IC50 = 0.88 μM.	27541357
MCF7	Antiproliferative assay		48 hrs	Antiproliferative activity against human MCF7 cells after 48 hrs by CellTiter-Glo assay, IC50 = 0.85 μM.	27541357
Jurkat	Antiproliferative assay		48 hrs	Antiproliferative activity against human Jurkat cells after 48 hrs by CellTiter-Glo assay, IC50 = 0.839 μM.	27541357
PC3	Antiproliferative assay		48 hrs	Antiproliferative activity against human PC3 cells after 48 hrs by CellTiter-Glo assay, IC50 = 0.77 μM.	27541357
KMS-12-BM	Antiproliferative assay		48 hrs	Antiproliferative activity against human KMS-12-BM cells after 48 hrs by CellTiter-Glo assay, IC50 = 0.75 μM.	27541357
MCF7	Antiproliferative assay		72 hrs	Antiproliferative activity against human MCF7 cells after 72 hrs by MTT assay, IC50 = 0.29 μM.	27541357
HL60	Antiproliferative assay		48 hrs	Antiproliferative activity against human HL60 cells after 48 hrs by CellTiter-Glo assay, IC50 = 0.52 μM.	27541357
MOLM14	Antiproliferative assay		48 hrs	Antiproliferative activity against human MOLM14 cells harboring FLT3-ITD mutant after 48 hrs by CellTiter-Glo assay, IC50 = 0.079 μM.	27541357
HEL 92.1.7	Function assay		1 hr	Induction of JAK2 V617F mutant phosphorylation at Y1007/8 residues in HEL 92.1.7 cells after 1 hr by immunoblot method	27541357
HL60	Antiproliferative assay			Antiproliferative activity against human HL60 cells, IC50 = 1.78 μM.	28953386
Jurkat	Antiproliferative assay			Antiproliferative activity against human Jurkat cells, IC50 = 1.09 μM.	28953386
HL60	Antiproliferative assay			Antiproliferative activity against human HL60 cells, IC50 = 1.78 μM.	27541357
Jurkat	Antiproliferative assay			Antiproliferative activity against human Jurkat cells, IC50 = 1.09 μM.	27541357
他の多くの細胞株試験データをご覧になる場合はこちらをクリックして下さい

生物活性

製品説明

Pacritinib 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 in cell-free assays, respectively. Phase 3.

特性

Dual JAK2/FLT3 inhibitor that has progressed to Phase III clinical trials for treatment of Myelofibrosis.

Targets

FLT3 (D835Y) ^[1] (Cell-free assay)	JAK2 (V617F) ^[1] (Cell-free assay)	FLT3 ^[1] (Cell-free assay)	JAK2 ^[1] (Cell-free assay)	TYK2 ^[1] (Cell-free assay)	もっとクリックする
6 nM	19 nM	22 nM	23 nM	50 nM	もっとクリックする

In Vitro
In vitro	Pacritinib is a potent inhibitor of both wild-type JAK2 and JAK2^V617F mutant (IC50= 19 nM) that is present in high frequencies among patients with MPD. Relative to JAK2, Pacritinib is two-fold less potent against TYK2 (IC50= 50 nM), 23-fold less potent against JAK3 (IC50= 520 nM) and 56-fold less potent against JAK1 (IC50= 1280 nM). Pacritinib effectively permeates cells to modulate signaling pathways downstream of JAK2, whether agonist activated or mutationally activated. Pacritinib induces apoptosis, cell cycle arrest and antiproliferative effects in JAK2^WT- and JAK2^V617F-dependent cells. Pacritinib inhibits cell proliferation of Karpas 1106P and Ba/F3-JAK2^V617F with IC50 of 348 and 160 nM, respectively. Pacritinib inhibits endogenous colony growth derived from erythroid and myeloid progenitors with IC50 of 63 and 53 nM , respectively. ^[1] SB1518 also inhibits FLT3 and its mutant FLT3-D835Y(IC50= 6 nM ). Pacritinib inhibits FLT3 phosphorylation and downstream STAT, MAPK and PI3K signaling in FLT3-internal-tandem duplication (ITD), FLT3-wt cells and primary AML blast cells. Pacritinib treatment leads to a dose-dependent decrease of pFLT3, pSTAT5, pERK1/2 and pAkt in FLT3-ITD harboring MV4-11 cells with IC50 of 80, 40, 33 and 29 nM , respectively. Treatment of the primary AML blast cells with Pacritinib for 3 h leads to a dose-dependent decrease of pFLT3, pSTAT3 and pSTAT5 with an IC50 below 0.5 μM. Pacritinib induces apoptosis, cell cycle arrest and anti-proliferative effects in FLT3-mutant and FLT3-wt cells. Pacritinib inhibits cell proliferation of FLT3-ITD-harboring cells MV4-11 and primary AML blast cells with IC50s of 47 nM and 0.19-1.3 μM, respectively. ^[2]
Kinase Assay	kinase activity assays
Kinase Assay	All assays are carried out in 384-well white microtiter plates. Compounds are 4-fold serially diluted in 8 steps, starting from 10 μM. The reaction mixture consisted of 25 μL assay buffer (50 mM HEPES pH 7.5, 10 mM MgCl₂, 5 mM MnCl₂, 1 mM DTT, 0.1 mM Na₃VO₄, 5 mM β-glycerol phosphate). For FLT3 assays, the reaction contains 2.0 μg/mL FLT3 enzyme, 5 μM of poly(Glu,Tyr) substrate and 4 μM of ATP. For JAK1 assays, the reaction contains 2.5 μg/mL of JAK1 enzyme, 10 μM of poly(Glu,Ala,Tyr) substrate and 1.0 μM of ATP. For JAK2 assays, the reaction contained 0.35 μg/mL of JAK2 enzyme, 10 μM of poly (Glu,Ala,Tyr) substrate and 0.15 μM of ATP. For JAK3 assays, the reaction contained 3.5 μg/mL of JAK3 enzyme, 10 μM of poly (Glu,Ala,Tyr) substrate and 6.0 μM of ATP. For TYK2 assays, the reaction contained 2.5 μg/mL of TYK2 enzyme, 10 μM of poly (Glu,Ala,Tyr) substrate and 0.15 μM of ATP. The reaction is incubated at room temperature for 2 h prior to addition of 13 μL PKLight^® detection reagent. After 10 min incubation luminescent signals are read on a multi-label plate reader.
細胞実験	細胞株	Karpas 1106P cells
	濃度	~10 μM
	反応時間	2 days
	実験の流れ	Cells are seeded at 30-50% confluency in 96-well plates and are treated with different concentrations of compounds (in triplicate) for 48 h. Cell viability is monitored using the CellTiter-Glo assay.
実験結果図	Methods	Biomarkers	結果図	PMID
	Western blot	pFLT3 / FLT3 / pSTAT5 / STAT5 / GAPDH p-STAT3Y705 / STAT3 / ACTIN / PARP pSTAT3 Y705 / STAT3 / β-Tubulin pSTAT3 Y705 / STAT3 / Actin / MAPK / p-AKT S473 / AKT pFLT3(Y591) / pSTAT5(Y694) / pERK1、2 / pAkt(T308) / β-Actin pFLT3(Y591) / pSTAT5(Y694) / pERK1、2 / pAkt(T308) / β-Actin		31102119
	Growth inhibition assay	Cell viability		29235481
	IHC	HE staining of liver sections HE staining of skin grafts p-STAT3 / Ki-67 / mCD31 / VEGF-A / Bcl-2		29785143
	Immunofluorescence	Phalloidin TUNEL		27334834

In Vivo
In Vivo	Pacritinib administrated at 150 mg/kg p.o. q.d. to JAK2^V617F-dependent xenograft model, significantly ameliorates splenomegaly and hepatomegaly symptoms, with 60% normalization of spleen weight and 92% normalization of liver weight and is well tolerated without significant weight loss or any hematological toxicities, including thrombocytopenia and anemia. Pacritinib induces dose-dependent inhibition of tumor growth of JAK2^V617F-dependent SET-2 xenograft model (40% for 75 mg/kg and 61% for 150 mg/kg). ^[1] Pacritinib is efficacious in FLT3-ITD-bearing MV4-11 xenograft models. Pacritinib treated once daily for 21 consecutive days, induces dose-dependent inhibition of tumor growth (38% for 25 mg/kg, 92% for 50 mg/kg and 121% for 100 mg/kg). Complete regression is observed in 3/10 and 8/8 mice for the 50 and 100 mg/kg/day groups, respectively. ^[2]
動物実験	動物モデル	Human megakaryoblastic leukemia xenografts SET-2
	投与量	150 mg/kg
	投与経路	oral gavage

NCT Number	Recruitment	Conditions	Sponsor/Collaborators	Start Date	Phases
臨床試験 (data from https://clinicaltrials.gov, updated on 2024-05-22)
NCT06303193	Not yet recruiting	Myelodysplastic Syndromes	National Cancer Institute (NCI)\|National Institutes of Health Clinical Center (CC)	May 15 2024	Phase 1\|Phase 2
NCT06052618	Not yet recruiting	KSHV Inflammatory Cytokine Syndrome (KICS)\|Kaposi Sarcoma Herpesvirus -Associated Multicentric Castleman Disease	National Cancer Institute (NCI)\|National Institutes of Health Clinical Center (CC)	May 15 2024	Phase 2
NCT06159491	Not yet recruiting	Chronic Myelomonocytic Leukemia	Douglas Tremblay\|Sobi Inc.\|Icahn School of Medicine at Mount Sinai	January 2 2024	Phase 1\|Phase 2
NCT05531786	Recruiting	Graft vs Host Disease	National Cancer Institute (NCI)\|National Institutes of Health Clinical Center (CC)	March 6 2023	Phase 1\|Phase 2

参考
[1] Hart S, et al. Leukemia, 2011, 25(11), 1751-1759. [2] Hart S, et al. Blood Cancer J, 2011, 1(11), e44.

参考

化学情報

分子量	472.58	化学式	C₂₈H₃₂N₄O₃
CAS No.	937272-79-2	SDF	Download Pacritinib SDFをダウンロードする
Smiles	C1CCN(C1)CCOC2=C3COCC=CCOCC4=CC(=CC=C4)C5=NC(=NC=C5)NC(=C3)C=C2
保管	3年-20°C粉	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年-20°C粉	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ケ月-20°Cin solvent

In vitro
Batch:

DMSO : 11 mg/mL ( (23.27 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。

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