Name: Pacritinib
Brand: Selleck Chemicals
SKU: S8057
Rating: 5 (15 reviews)

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.

Pacritinib Chemical Structure

CAS: 937272-79-2

Selleck's Pacritinib has been cited by 15 Publications

1 Customer Review

Purity & Quality Control

Batch: Purity: 99.94%

99.94

Products often used together with Pacritinib

Fedratinib (TG101348)

Pacritinib and Fedratinib are JAK inhibitors that have been approved for the treatment of myelofibrosis.

Waksal JA, et al. Curr Hematol Malig Rep. 2022 Oct;17(5):140-154.

TMZ(Temozolomide)

Pacritinib and Temozolomide use shows BBB penetration and improves overall median survival in an orthotopic xenograft mice model.

Jensen KV, et al. PLoS One. 2017 Dec 18;12(12):e0189670.

Rapamycin (Sirolimus)

Pacritinib and Sirolimus use enhances suppression over human T cells in xenogeneic GVHD models and in vitro.

Pidala J, et al. Clin Cancer Res. 2021 May 15;27(10):2712-2722.

Ruxolitinib

Pacritinib protects the differentiation and upregulation of costimulatory molecules of human dendritic cells (DCs), whereas ruxolitinib heavily impairs their differentiation and function.

Heine A, et al. Exp Hematol. 2021 Aug;100:37-40.

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 Related Products

Related Targets	JAK1 JAK2 JAK3 Tyk2	Click to Expand
Related Compound Libraries	Kinase Inhibitor Library FDA-approved Drug Library Natural Product Library Tyrosine Kinase Inhibitor Library JAK/STAT compound library	Click to Expand

Signaling Pathway

JAK Signaling Pathway

Choose Selective JAK Inhibitors

Cell Data

Cell Lines	Assay Type	Concentration	Incubation Time	Activity Description	PMID
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
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
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
PC3	Antiproliferative assay		48 hrs	Antiproliferative activity against human PC3 cells after 48 hrs by CellTiter-Glo assay, IC50 = 0.77 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
MCF7	Antiproliferative assay		48 hrs	Antiproliferative activity against human MCF7 cells after 48 hrs by CellTiter-Glo assay, IC50 = 0.85 μM.	27541357
HCT116	Antiproliferative assay		72 hrs	Antiproliferative activity against human HCT116 cells after 72 hrs by MTT assay, IC50 = 0.88 μM.	27541357
Jurkat	Antiproliferative assay			Antiproliferative activity against human Jurkat cells, IC50 = 1.09 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
OPM2	Antiproliferative assay		48 hrs	Antiproliferative activity against human OPM2 cells after 48 hrs by CellTiter-Glo assay, IC50 = 1.21 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
KG1	Antiproliferative assay		48 hrs	Antiproliferative activity against human KG1 cells after 48 hrs by CellTiter-Glo assay, IC50 = 1.48 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
HCT116	Antiproliferative assay		48 hrs	Antiproliferative activity against human HCT116 cells after 48 hrs by CellTiter-Glo assay, IC50 = 1.69 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
HL60	Antiproliferative assay			Antiproliferative activity against human HL60 cells, IC50 = 1.78 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
TAMH	Antiproliferative assay		24 hrs	Antiproliferative activity against mouse TAMH cells after 24 hrs by CellTiter-Glo assay, IC50 = 3.68 μM.	27541357
MOLM14	Antiproliferative assay		48 hrs	Antiproliferative activity against human MOLM14 cells after 48 hrs by CellTiter-Glo luminescent assay, IC50 = 0.079 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
Jurkat	Antiproliferative assay			Antiproliferative activity against human Jurkat cells, IC50 = 1.09 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
OPM2	Antiproliferative assay		48 hrs	Antiproliferative activity against human OPM2 cells after 48 hrs by CellTiter-Glo luminescent assay, IC50 = 1.21 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
KG1	Antiproliferative assay		48 hrs	Antiproliferative activity against human KG1 cells after 48 hrs by CellTiter-Glo luminescent assay, IC50 = 1.48 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
HL60	Antiproliferative assay			Antiproliferative activity against human HL60 cells, IC50 = 1.78 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
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
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
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
Click to View More Cell Line Experimental Data

Biological Activity

Description

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.

Features

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)	Click to View More Targets
6 nM	19 nM	22 nM	23 nM	50 nM	Click to View More Targets

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.
Cell Research	Cell lines	Karpas 1106P cells
	Concentrations	~10 μM
	Incubation Time	2 days
	Method	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.
Experimental Result Images	Methods	Biomarkers	Images	PMID
	Western blot	pFLT3(Y591) / pSTAT5(Y694) / pERK1、2 / pAkt(T308) / β-Actin pFLT3(Y591) / pSTAT5(Y694) / pERK1、2 / pAkt(T308) / β-Actin pSTAT3 Y705 / STAT3 / Actin / MAPK / p-AKT S473 / AKT pSTAT3 Y705 / STAT3 / β-Tubulin p-STAT3Y705 / STAT3 / ACTIN / PARP pFLT3 / FLT3 / pSTAT5 / STAT5 / GAPDH		22829080
	Growth inhibition assay	Cell viability		29235481
	IHC	p-STAT3 / Ki-67 / mCD31 / VEGF-A / Bcl-2 HE staining of skin grafts HE staining of liver sections		32929154
	Immunofluorescence	TUNEL Phalloidin		32929154

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]
Animal Research	Animal Models	Human megakaryoblastic leukemia xenografts SET-2
	Dosages	150 mg/kg
	Administration	oral gavage

NCT Number	Recruitment	Conditions	Sponsor/Collaborators	Start Date	Phases
Clinical Trial Information (data from https://clinicaltrials.gov, updated on 2024-01-11)
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
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)	January 12 2024	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
NCT04520269	Unknown status	Breast Cancer	National University Hospital Singapore	July 13 2020	Phase 1\|Phase 2

References

Chemical Information & Solubility

Molecular Weight	472.58	Formula	C₂₈H₃₂N₄O₃
CAS No.	937272-79-2	SDF	Download Pacritinib SDF
Smiles	C1CCN(C1)CCOC2=C3COCC=CCOCC4=CC(=CC=C4)C5=NC(=NC=C5)NC(=C3)C=C2
Storage (From the date of receipt)	3 years-20°Cpowder	Storage of Stock Solutions Aliquot the stock solutions to avoid repeated freeze-thaw cycles	1 year-80°Cin solvent
Storage (From the date of receipt)	3 years-20°Cpowder		1 month-20°Cin solvent

In vitro
Batch:

DMSO : 11 mg/mL ( (23.27 mM)； Moisture-absorbing DMSO reduces solubility. Please use fresh DMSO.)

Water : Insoluble

Ethanol : Insoluble

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In vivo
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