Pacritinib

別名: SB1518

目錄號(hào)：S8057 Purity: 99.94%

Pacritinib是有效的選擇性Janus Kinase 2 (JAK2)和Fms-Like Tyrosine Kinase-3 (FLT3)抑制劑，無(wú)細(xì)胞試驗(yàn)中IC50分別為23和22 nM。Phase 3。

Pacritinib Chemical Structure

CAS: 937272-79-2

規(guī)格	價(jià)格	庫(kù)存
10mM (1mL in DMSO)	3677.31	現(xiàn)貨
5mg	2438.19	現(xiàn)貨
50mg	7770	現(xiàn)貨
1g	39900	現(xiàn)貨
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產(chǎn)品質(zhì)控

批次：純度： 99.94%

99.94

常與Pacritinib一起在實(shí)驗(yàn)中被使用的化合物

Fedratinib (TG101348)

Pacritinib和Fedratinib是JAK抑制劑，已被批準(zhǔn)用于治療骨髓纖維化。

TMZ(Temozolomide)

Pacritinib和Temozolomide的使用顯示了BBB滲透并改善了原位異種移植小鼠模型中的總體中位生存期。

Rapamycin (Sirolimus)

Pacritinib和Rapamycin的使用增強(qiáng)了異種GVHD模型和體外對(duì)人類T細(xì)胞的抑制。

Ruxolitinib (INCB18424)

Pacritinib可保護(hù)人樹(shù)突狀細(xì)胞(DC)共刺激分子的分化和上調(diào)，而Rruxolitinib會(huì)嚴(yán)重?fù)p害其分化和功能。

Pracinostat (SB939)

Pacritinib和Pracinostat完全消除JAK2自磷酸化并增強(qiáng)Set-2細(xì)胞的細(xì)胞死亡。

Pacritinib相關(guān)產(chǎn)品

相關(guān)靶點(diǎn)	JAK1 JAK2 JAK3 Tyk2	點(diǎn)擊展開(kāi)
相關(guān)產(chǎn)品	AZD1480 WP1066 Momelotinib (CYT387) Filgotinib (GLPG0634) AT9283 Gandotinib (LY2784544) TG101209 Cerdulatinib (PRT062070) hydrochloride NVP-BSK805 2HCl WHI-P154 FLLL32 CEP-33779 Decernotinib (VX-509) AZ 960 ZM 39923 HCl Cerdulatinib (PRT062070) BMS-911543 XL019 Curcumol Solcitinib Oclacitinib?maleate Pyridone 6 Creatine Ritlecitinib (PF-06651600) Itacitinib (INCB39110) Deucravacitinib (BMS-986165) Peficitinib (ASP015K) FM-381 WHI-P97 1,2,3,4,5,6-Hexabromocyclohexane JANEX-1 Brepocitinib (PF-06700841) Selective JAK3 inhibitor 1 SAR-20347 BD750 Brevilin A	點(diǎn)擊展開(kāi)
相關(guān)化合物庫(kù)	激酶抑制劑庫(kù) FDA藥物庫(kù) 天然產(chǎn)物庫(kù) 酪氨酸激酶抑制劑分子庫(kù) JAK-STAT信號(hào)通路庫(kù)	點(diǎn)擊展開(kāi)

細(xì)胞實(shí)驗(yàn)數(shù)據(jù)示例

細(xì)胞系	實(shí)驗(yàn)類型	給藥濃度	孵育時(shí)間	活性描述	文獻(xiàn)信息(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
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生物活性

產(chǎn)品描述

Pacritinib是有效的選擇性Janus Kinase 2 (JAK2)和Fms-Like Tyrosine Kinase-3 (FLT3)抑制劑，無(wú)細(xì)胞試驗(yàn)中IC50分別為23和22 nM。Phase 3。

特性

雙重JAK2/FLT3抑制劑，治療骨髓纖維化正處于3期臨床階段。

靶點(diǎn)

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)	點(diǎn)擊更多
6 nM	19 nM	22 nM	23 nM	50 nM	點(diǎn)擊更多

體外研究(In Vitro)
體外研究活性	Pacritinib是野生型JAK2和JAK2^V617F的抑制劑（IC 50是19 nM），它高頻率存在于MPD患者中。相對(duì)于JAK2，Pacritinib對(duì)TYK2（IC 50是50 nM）的抑制作用低2倍，對(duì)JAK3（IC 50是520 nM）的抑制作用低23倍，對(duì)JAK1（IC 50是50 nM）的抑制作用低56倍。Pacritinib有效地滲透細(xì)胞調(diào)節(jié)JAK2的下游信號(hào)通路，無(wú)論是受體激動(dòng)劑激活或突變型激活。在JAK2^WT- and JAK2^V617F-缺少細(xì)胞中，Pacritinib誘導(dǎo)細(xì)胞凋亡，細(xì)胞周期阻滯和抗增殖作用。Pacritinib抑制Karpas 1106P and Ba/F3-JAK2^V617F細(xì)胞增殖，IC 50分別是348 nM和160 nM。Pacritinib從抑制紅細(xì)胞和髓系祖細(xì)胞來(lái)源的內(nèi)在性菌落生長(zhǎng)，IC50分別為63 nM和53 nM。^[1] SB1518也抑制FLT3基因及突變FLT3-D835Y（IC50是6 nM）。在FLT3基因內(nèi)部串聯(lián)重復(fù)（ITD），F(xiàn)LT3-野生型細(xì)胞和原發(fā)性AML原始細(xì)胞中，Pacritinib抑制FLT3磷酸化和下游STAT，MAPK和PI3K信號(hào)。在含F(xiàn)LT3-ITD的MV4-11細(xì)胞中，Pacritinib劑量依賴性減少pFLT3，pSTAT5，PERK1/ 2和pAKT，IC50分別為80 nM，40 nM，33 nM和29 nM。Pacritinib處理原代AML細(xì)胞3小時(shí)劑量依賴性的減少pFLT3，pSTAT3和pSTAT5，IC 50低于0.5 μM。在FLT3突變和FLT3-wt細(xì)胞中，Pacritinib誘導(dǎo)細(xì)胞凋亡，細(xì)胞周期停滯和抗增殖作用。Pacritinib抑制含F(xiàn)LT3-ITD的MV4-11細(xì)胞和原代AML細(xì)胞增殖，IC50分別為47 nM 和0.19-1.3 nM。^[2]
激酶實(shí)驗(yàn)	激酶活性檢測(cè)
激酶實(shí)驗(yàn)	所有測(cè)定均在384孔白色微量滴定板中進(jìn)行。化合物4-倍系列稀釋8級(jí)，從10μM開(kāi)始。反應(yīng)混合物由25 μL的測(cè)定緩沖液（50 mM HEPES pH值為7.5 ，10mM氯化鎂，5 mM氯化錳，1 mM DTT， 0.1 mM的釩酸鈉，5 mM的β -甘油磷酸）。對(duì)FLT3的測(cè)定中，反應(yīng)含有2.0微克/毫升的FLT3酶，5 μM聚（谷氨酸，酪氨酸）底物和4 μM ATP。對(duì)于JAK1測(cè)定中，反應(yīng)含有2.5微克/毫升JAK1酶，10μM聚（谷氨酸，丙氨酸，酪氨酸）底物和1.0 μM ATP。對(duì)于JAK2測(cè)定中，反應(yīng)物含有0.35微克/毫升的JAK2酶，10 μM聚（谷氨酸，丙氨酸，酪氨酸），襯底和0.15 μM ATP。對(duì)于JAK3測(cè)定中，反應(yīng)物含有3.5微克/毫升的JAK3酶，10μM聚（谷氨酸，丙氨酸，酪氨酸）底物和6.0 μM的ATP。對(duì)TYK2測(cè)定中，反應(yīng)物含有2.5微克/毫升的TYK2酶，10μM聚（谷氨酸，丙氨酸，酪氨酸）底物和0.15 μM ATP。反應(yīng)在加入13 μL PKLight^?檢測(cè)試劑之前在室溫溫育2小時(shí)。溫育10分鐘之后讀取在多標(biāo)記平板讀數(shù)器讀取發(fā)光信號(hào)。
細(xì)胞實(shí)驗(yàn)	細(xì)胞系	Karpas 1106P細(xì)胞
	濃度	~10 μM
	孵育時(shí)間	2 天
	方法	細(xì)胞按30?50％密度接種在96孔板中，并用不同濃度的化合物（一式三份）處理48小時(shí)。細(xì)胞活力使用CellTiter-格洛測(cè)定檢測(cè)。
實(shí)驗(yàn)圖片	檢測(cè)方法	檢測(cè)指標(biāo)	實(shí)驗(yàn)圖片	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

體內(nèi)研究(In Vivo)
體內(nèi)研究活性	Pacritinib(150毫克/千克)口服q.d.到JAK2 V617F^{相關(guān)移植瘤模型中，可顯著改善脾腫大和肝的癥狀，使60％脾臟重量和92％肝臟重量的正常化，無(wú)顯著體重減輕或任何血液學(xué)毒性，包括血小板減少癥和貧血。 Pacritinib誘導(dǎo)劑量依賴性的抑制了JAK2^V617F依賴性的SET-2異種移植物的生長(zhǎng)（75毫克/千克時(shí)為40％和150毫克/千克時(shí)為61％）。^[1] Pacritinib對(duì) FLT3-ITD息MV4-11異種移植模型是有效的。 Pacritinib治療，每日一次，連續(xù)21天，誘導(dǎo)了劑量依賴性的腫瘤生長(zhǎng)抑制（25毫克/千克時(shí)為38％，50毫克/千克時(shí)為92％，100毫克/千克時(shí)為121％）。在50和100毫克/公斤/天組分別觀察到3/10和8/8只小鼠腫瘤完全消退。^[2]}
動(dòng)物實(shí)驗(yàn)	Animal Models	人巨核細(xì)胞白血病移植SET-2
	Dosages	150 mg/kg
	Administration	口服灌胃

NCT Number	Recruitment	Conditions	Sponsor/Collaborators	Start Date	Phases
臨床試驗(yàn)信息 (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

參考文獻(xiàn)
[1]https://pubmed.ncbi.nlm.nih.gov/21691275/ [2]https://pubmed.ncbi.nlm.nih.gov/22829080/

參考文獻(xiàn)

[1]https://pubmed.ncbi.nlm.nih.gov/21691275/
[2]https://pubmed.ncbi.nlm.nih.gov/22829080/

化學(xué)信息&溶解度

分子量	472.58	分子式	C₂₈H₃₂N₄O₃
CAS號(hào)	937272-79-2	SDF	Download Pacritinib SDF
Smiles	C1CCN(C1)CCOC2=C3COCC=CCOCC4=CC(=CC=C4)C5=NC(=NC=C5)NC(=C3)C=C2
儲(chǔ)存條件(自收到貨起)	3年-20°C粉狀	儲(chǔ)備液保存和期限建議分裝儲(chǔ)備液，避免反復(fù)凍融！	1年-80°C溶于溶劑
儲(chǔ)存條件(自收到貨起)	3年-20°C粉狀	儲(chǔ)備液保存和期限建議分裝儲(chǔ)備液，避免反復(fù)凍融！	1個(gè)月-20°C溶于溶劑

體外溶解度
批次：

DMSO : 11 mg/mL ( (23.27 mM) ；DMSO吸濕會(huì)降低化合物溶解度，請(qǐng)使用新開(kāi)封DMSO)

Water : Insoluble

Ethanol : Insoluble

DMSO : 11 mg/mL ( (23.27 mM) ；DMSO吸濕會(huì)降低化合物溶解度，請(qǐng)使用新開(kāi)封DMSO)

Water : Insoluble

Ethanol : Insoluble

DMSO : 12 mg/mL ( (25.39 mM) ；DMSO吸濕會(huì)降低化合物溶解度，請(qǐng)使用新開(kāi)封DMSO)

Water : Insoluble

Ethanol : Insoluble

摩爾濃度計(jì)算器

體內(nèi)溶解配方批次：現(xiàn)配現(xiàn)用，請(qǐng)按從左到右的順序依次添加，澄清后再加入下一溶劑				動(dòng)物體內(nèi)配方計(jì)算器
均勻懸濁液	CMC-NA	≥5mg/ml	以 1 mL 工作液為例，取 5 mg該產(chǎn)品加到 1 ml CMC-NA 溶液中，混合均勻，即可得工作液濃度為 5 mg/ml的均勻懸濁液。
均勻懸濁液	CMC-NA	≥5mg/ml	以 1 mL 工作液為例，取 5 mg該產(chǎn)品加到 1 ml CMC-NA 溶液中，混合均勻，即可得工作液濃度為 5 mg/ml的均勻懸濁液。
均勻懸濁液	CMC-NA	≥5mg/ml	以 1 mL 工作液為例，取 5 mg該產(chǎn)品加到 1 ml CMC-NA 溶液中，混合均勻，即可得工作液濃度為 5 mg/ml的均勻懸濁液。
澄清溶液	5%DMSO 1 Corn oil 該配方已經(jīng)過(guò)Selleck實(shí)驗(yàn)室實(shí)測(cè)。如果上述溶解方案不能滿足您的需求，可聯(lián)系Selleck銷售提供定制化測(cè)試。	0.150mg/ml (0.32mM)	以 1 mL 工作液為例，取50μL3mg/ml的澄清DMSO儲(chǔ)備液加到950μL玉米油中，混合均勻。工作液請(qǐng)現(xiàn)配現(xiàn)用！

實(shí)驗(yàn)計(jì)算

摩爾濃度計(jì)算器

質(zhì)量	濃度	體積	分子量
=	×	×

稀釋計(jì)算器分子量計(jì)算器

動(dòng)物體內(nèi)配方計(jì)算器（澄清溶液）

第一步：請(qǐng)輸入基本實(shí)驗(yàn)信息（考慮到實(shí)驗(yàn)過(guò)程中的損耗，建議多配一只動(dòng)物的藥量）

給藥劑量 mg/kg 動(dòng)物平均體重 g 每只動(dòng)物給藥體積 μL 動(dòng)物數(shù)量只

第二步：請(qǐng)輸入動(dòng)物體內(nèi)配方組成（配方適用于不溶于水的藥物；不同批次藥物配方比例不同，請(qǐng)聯(lián)系Selleck為您提供正確的澄清溶液配方）

% DMSO + % + % Tween 80 + % ddH2O

%DMSO+ %

計(jì)算結(jié)果：

工作液濃度： mg/ml；

DMSO母液配制方法： mg 藥物溶于μL DMSO溶液（母液濃度mg/mL，注：如該濃度超過(guò)該批次藥物DMSO溶解度，請(qǐng)先聯(lián)系Selleck）；

體內(nèi)配方配制方法：取μL DMSO母液，加入μL PEG300，混勻澄清后加入μL Tween 80，混勻澄清后加入μL ddH₂O，混勻澄清。

體內(nèi)配方配制方法：取μL DMSO母液，加入μL Corn oil，混勻澄清。

注意：1. 首先保證母液是澄清的；
2.一定要按照順序依次將溶劑加入，進(jìn)行下一步操作之前必須保證上一步操作得到的是澄清的溶液，可采用渦旋、超聲或水浴加熱等物理方法助溶。

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Pacritinib

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常與Pacritinib一起在實(shí)驗(yàn)中被使用的化合物

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