Name: Pacritinib (SB1518)
Brand: Selleck Chemicals
SKU: S8057
Rating: 5 (23 reviews)

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Qualitätskontrolle (Quality Control)

Charge: Reinheit: 99.94%

99.94

Produkte, die oft zusammen verwendet werden mit Pacritinib (SB1518)

Pracinostat (SB939)

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

Verwandte Targets	EGFR STAT Pim
Andere JAK Inhibitors	BMS-986165 (Deucravacitinib) AZD1480 WP1066 Momelotinib (CYT387) Filgotinib (GLPG0634) AT9283 Gandotinib (LY2784544) NVP-BSK805 2HCl TG101209 Cerdulatinib (PRT062070) hydrochloride

Zellkultur, Behandlung & Arbeitskonzentration
(Cell Culture, Treatment & Working Concentration)

Zelllinien	Assay-Typ	Konzentration	Inkubationszeit	Aktivitätsbeschreibung	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
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Chemische Informationen, Lagerung & Stabilität (Chemical Information, Storage & Stability)

Molekulargewicht	472.58	Formel	C₂₈H₃₂N₄O₃	Lagerung (Ab Erhaltdatum)	3 Jahre-20°CPulver
CAS-Nr.	937272-79-2	SDF herunterladen		Lagerung von Stammlösungen	1 Jahr-80°Cin Lösungsmittel 1 Monat-20°Cin Lösungsmittel
Synonyme	SB1518			Smiles	C1CCN(C1)CCOC2=C3COCC=CCOCC4=CC(=CC=C4)C5=NC(=NC=C5)NC(=C3)C=C2

Löslichkeit (Solubility)

In vitro
Charge:

DMSO : 11 mg/mL (23.27 mM)
(Feuchtigkeitskontaminiertes DMSO kann die Löslichkeit verringern. Verwenden Sie frisches, wasserfreies DMSO.)

Water : Insoluble

Ethanol : Insoluble

DMSO : 11 mg/mL (23.27 mM)
(Feuchtigkeitskontaminiertes DMSO kann die Löslichkeit verringern. Verwenden Sie frisches, wasserfreies DMSO.)

Water : Insoluble

Ethanol : Insoluble

DMSO : 12 mg/mL (25.39 mM)
(Feuchtigkeitskontaminiertes DMSO kann die Löslichkeit verringern. Verwenden Sie frisches, wasserfreies DMSO.)

Water : Insoluble

Ethanol : Insoluble

Molaritätsrechner

Masse	Konzentration	Volumen	Molekulargewicht
=	×	×

Verdünnungsrechner Molekulargewicht-Rechner

In vivo Charge:
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Clear solution	5%DMSO 1 Corn oil Von Selleck-Laboren validiert. Sollten Sie Anpassungen an dieser Formulierung benötigen, wenden Sie sich für kundenspezifische Tests an unser Vertriebsteam.	0.150mg/ml (0.32mM)	Taking the 1 mL working solution as an example, add 50 μL of 3 mg/ml clear DMSO stock solution to 950 μL of corn oil and mix evenly. The mixed solution should be used immediately for optimal results.

In-vivo-Formulierungsrechner (Klare Lösung)

Schritt 1: Geben Sie unten die Informationen ein (Empfohlen: Ein zusätzliches Tier einplanen, um Verluste während des Experiments auszugleichen)

Dosierung: mg/kg Durchschnittliches Gewicht der Tiere: g Dosierungsvolumen pro Tier:μL Anzahl der Tiere:

Schritt 2: Geben Sie die In-vivo-Formulierung ein (Dies ist nur der Rechner, nicht die Formulierung. Bitte kontaktieren Sie uns zuerst, wenn im Abschnitt Löslichkeit keine In-vivo-Formulierung angegeben ist.)

% DMSO + % + % Tween 80 + % ddH₂O

%DMSO+ %

Berechnungsergebnisse:

Arbeitskonzentration: mg/ml;

Methode zur Herstellung der DMSO-Stammflüssigkeit: mg Wirkstoff voraufgelöst in μL DMSO ( Konzentration der Stammflüssigkeit mg/mL, Bitte kontaktieren Sie uns zuerst, wenn die Konzentration die DMSO-Löslichkeit der jeweiligen Wirkstoffcharge überschreitet. )

Methode zur Herstellung der In-vivo-Formulierung: Nehmen Sie μL DMSO Stammflüssigkeit, fügen Sie als Nächstes hinzuμL PEG300, mischen und aufklären, fügen Sie als Nächstes hinzuμL Tween 80, mischen und aufklären, fügen Sie als Nächstes hinzu μL ddH₂O, mischen und aufklären.

Methode zur Herstellung der In-vivo-Formulierung: Nehmen Sie μL DMSO Stammflüssigkeit, fügen Sie als Nächstes hinzu μL Maisöl, mischen und aufklären.

Hinweis: 1. Bitte stellen Sie sicher, dass die Flüssigkeit klar ist, bevor Sie das nächste Lösungsmittel hinzufügen.
2. Achten Sie darauf, die Lösungsmittel in der richtigen Reihenfolge hinzuzufügen. Sie müssen sicherstellen, dass die im vorherigen Schritt erhaltene Lösung klar ist, bevor Sie das nächste Lösungsmittel hinzufügen. Physikalische Methoden wie Vortexen, Ultraschall oder ein warmes Wasserbad können zur Unterstützung des Lösungsvorgangs verwendet werden.

Wirkungsmechanismus (Mechanism of Action)

Eigenschaften	Dual JAK2/FLT3 inhibitor that has progressed to Phase III clinical trials for treatment of Myelofibrosis.
Targets/IC₅₀/Ki	FLT3 (D835Y) (Cell-free assay) 6 nM JAK2 (V617F) (Cell-free assay) 19 nM FLT3 (Cell-free assay) 22 nM JAK2 (Cell-free assay) 23 nM TYK2 (Cell-free assay) 50 nM JAK3 (Cell-free assay) 520 nM
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, this compound 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). It effectively permeates cells to modulate signaling pathways downstream of JAK2, whether agonist activated or mutationally activated. This chemical induces apoptosis, cell cycle arrest and antiproliferative effects in JAK2^WT- and JAK2^V617F-dependent cells. It inhibits cell proliferation of Karpas 1106P and Ba/F3-JAK2^V617F with IC50 of 348 and 160 nM, respectively. It inhibits endogenous colony growth derived from erythroid and myeloid progenitors with IC50 of 63 and 53 nM , respectively. SB1518 also inhibits FLT3 and its mutant FLT3-D835Y(IC50= 6 nM ). This compound inhibits FLT3 phosphorylation and downstream STAT, MAPK and PI3K signaling in FLT3-internal-tandem duplication (ITD), FLT3-wt cells and primary AML blast cells. Its 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 this chemical for 3 h leads to a dose-dependent decrease of pFLT3, pSTAT3 and pSTAT5 with an IC50 below 0.5 μM. It induces apoptosis, cell cycle arrest and anti-proliferative effects in FLT3-mutant and FLT3-wt cells. It 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.
Kinase-Assay	Kinase-Aktivitätsassays
Kinase-Assay	Alle Assays werden in weißen 384-Well-Mikrotiterplatten durchgeführt. Die Verbindungen werden in 8 Schritten 4-fach seriell verdünnt, ausgehend von 10 μM. Das Reaktionsgemisch bestand aus 25 μL Assay-Puffer (50 mM HEPES pH 7,5, 10 mM MgCl₂, 5 mM MnCl₂, 1 mM DTT, 0,1 mM Na₃VO₄, 5 mM β-Glycerophosphat). Für FLT3-Assays enthält die Reaktion 2,0 μg/mL FLT3-Enzym, 5 μM poly(Glu,Tyr)-Substrat und 4 μM ATP. Für JAK1-Assays enthält die Reaktion 2,5 μg/mL JAK1-Enzym, 10 μM poly(Glu,Ala,Tyr)-Substrat und 1,0 μM ATP. Für JAK2-Assays enthielt die Reaktion 0,35 μg/mL JAK2-Enzym, 10 μM poly(Glu,Ala,Tyr)-Substrat und 0,15 μM ATP. Für JAK3-Assays enthielt die Reaktion 3,5 μg/mL JAK3-Enzym, 10 μM poly(Glu,Ala,Tyr)-Substrat und 6,0 μM ATP. Für TYK2-Assays enthielt die Reaktion 2,5 μg/mL TYK2-Enzym, 10 μM poly(Glu,Ala,Tyr)-Substrat und 0,15 μM ATP. Die Reaktion wird vor der Zugabe von 13 μL PKLight^®-Detektionsreagenz 2 Stunden lang bei Raumtemperatur inkubiert. Nach 10 Minuten Inkubation werden die Lumineszenzsignale auf einem Multi-Label-Plattenlesegerät gemessen.
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. This compound 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). This chemical is efficacious in FLT3-ITD-bearing MV4-11 xenograft models. It 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.
Referenzen	[1] https://pubmed.ncbi.nlm.nih.gov/21691275/ [2] https://pubmed.ncbi.nlm.nih.gov/22829080/

Anwendungen (Applications)

Methoden	Biomarker	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

Informationen zu klinischen Studien (Clinical Trial Information)

(Daten von https://clinicaltrials.gov, aktualisiert am 2024-05-22)

NCT-Nummer	Rekrutierung	Bedingungen	Sponsor/Kollaboratoren	Startdatum	Phases
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

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):

Pacritinib (SB1518) JAK2/FLT3-Inhibitor

Molekulargewicht: 472.58

Qualitätskontrolle (Quality Control)

Produkte, die oft zusammen verwendet werden mit Pacritinib (SB1518)

Zellkultur, Behandlung & Arbeitskonzentration
(Cell Culture, Treatment & Working Concentration)

Chemische Informationen, Lagerung & Stabilität (Chemical Information, Storage & Stability)

Löslichkeit (Solubility)

Molaritätsrechner

In-vivo-Formulierungsrechner (Klare Lösung)

Wirkungsmechanismus (Mechanism of Action)

Anwendungen (Applications)

Informationen zu klinischen Studien (Clinical Trial Information)

Pacritinib (SB1518) JAK2/FLT3-Inhibitor

Molekulargewicht: 472.58

Qualitätskontrolle (Quality Control)

Produkte, die oft zusammen verwendet werden mit Pacritinib (SB1518)

Zellkultur, Behandlung & Arbeitskonzentration (Cell Culture, Treatment & Working Concentration)

Chemische Informationen, Lagerung & Stabilität (Chemical Information, Storage & Stability)

Löslichkeit (Solubility)

Molaritätsrechner

In-vivo-Formulierungsrechner (Klare Lösung)

Wirkungsmechanismus (Mechanism of Action)

Anwendungen (Applications)

Informationen zu klinischen Studien (Clinical Trial Information)

Zellkultur, Behandlung & Arbeitskonzentration
(Cell Culture, Treatment & Working Concentration)