NVP-BSK805 dihydrochloride | CAS#1942919-79-0 | JAK2 inhibitor

MedKoo Cat#: 462550 | Name: NVP-BSK805 dihydrochloride

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Description:

WARNING: This product is for research use only, not for human or veterinary use.

NVP-BSK805 dihydrochloride is an ATP-competitive JAK2 inhibitor.

Chemical Structure

NVP-BSK805 dihydrochloride

CAS#1942919-79-0 (HCl)

Theoretical Analysis

MedKoo Cat#: 462550

Name: NVP-BSK805 dihydrochloride

CAS#: 1942919-79-0 (HCl)

Chemical Formula: C27H30Cl2F2N6O

Exact Mass: 562.1826

Molecular Weight: 563.47

Elemental Analysis: C, 57.55; H, 5.37; Cl, 12.58; F, 6.74; N, 14.91; O, 2.84

Price and Availability

Size	Price	Availability	Quantity
5mg	USD 350.00	2 Weeks
10mg	USD 540.00	2 Weeks

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Related CAS #

1092499-93-8 (free base) 1942919-79-0 (HCl)

Synonym

NVP-BSK805 dihydrochloride; NVP BSK805 dihydrochloride; NVPBSK805 dihydrochloride

IUPAC/Chemical Name

4-(2,6-difluoro-4-(3-(1-(piperidin-4-yl)-1H-pyrazol-4-yl)quinoxalin-5-yl)benzyl)morpholine dihydrochloride

InChi Key

NUOCAPALWRHKCU-UHFFFAOYSA-N

InChi Code

InChI=1S/C27H28F2N6O.2ClH/c28-23-12-18(13-24(29)22(23)17-34-8-10-36-11-9-34)21-2-1-3-25-27(21)33-26(15-31-25)19-14-32-35(16-19)20-4-6-30-7-5-20;;/h1-3,12-16,20,30H,4-11,17H2;2*1H

SMILES Code

FC1=C(CN2CCOCC2)C(F)=CC(C3=C4N=C(C5=CN(C6CCNCC6)N=C5)C=NC4=CC=C3)=C1.Cl.Cl

Appearance

Solid powder

Purity

>98% (or refer to the Certificate of Analysis)

Shipping Condition

Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition

Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility

Soluble in DMSO

Shelf Life

>3 years if stored properly

Drug Formulation

This drug may be formulated in DMSO

Stock Solution Storage

0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code

2934.99.9001

More Info

Product Data

Product Data

Instruction

View handling instruction

Biological target:

NVP-BSK805 dihydrochloride is an ATP-competitive JAK2 inhibitor, with IC50s of 0.48 nM, 31.63 nM, 18.68 nM, and 10.76 nM for JAK2 JH1 (JAK homology 1), JAK1 JH1, JAK3 JH1, and TYK2 JH1, respectively.

In vitro activity:

This study reports potent inhibition of JAK2(V617F) and JAK2 wild-type enzymes by a novel substituted quinoxaline, NVP-BSK805, which acts in an ATP-competitive manner. Within the JAK family, NVP-BSK805 displays more than 20-fold selectivity towards JAK2 in vitro, as well as excellent selectivity in broader kinase profiling. The compound blunts constitutive STAT5 phosphorylation in JAK2(V617F)-bearing cells, with concomitant suppression of cell proliferation and induction of apoptosis. Reference: Mol Cancer Ther. 2010 Jul;9(7):1945-55. https://pubmed.ncbi.nlm.nih.gov/20587663/

In vivo activity:

To test this, C57BL/6J chow-fed mice received either chronic intraperitoneal (ip) or repeated intracerebroventricular (icv) administration of the selective Jak2 inhibitor NVP-BSK805, which was proven efficacious in treating polycythemia in rodents. This study found that chronic peripheral administration of NVP-BSK805 did not alter food intake, but increased fat mass and feed efficiency. Accordingly, acute icv administration of NVP-BSK805 prevented the ability of leptin to decrease food intake and body weight by impeding STAT3 phosphorylation within the hypothalamus. Consequently, acute icv administration of NVP-BSK805 at higher dose induced hyperphagia and body weight gain. Reference: Front Pharmacol. 2018 May 15;9:527. https://pubmed.ncbi.nlm.nih.gov/29867515/

	Solvent	mg/mL	mM
Solubility
	DMF	20.0	35.49
	DMSO	58.3	103.52
	Ethanol	3.5	6.21
	PBS (pH 7.2)	10.0	17.75
	Water	100.0	177.47

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 563.47 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Concentration / Solvent Volume / Mass	1 mg	5 mg	10 mg
1 mM	1.15 mL	5.76 mL	11.51 mL
5 mM	0.23 mL	1.15 mL	2.3 mL
10 mM	0.12 mL	0.58 mL	1.15 mL
50 mM	0.02 mL	0.12 mL	0.23 mL

Formulation protocol:

1. Baffert F, Régnier CH, De Pover A, Pissot-Soldermann C, Tavares GA, Blasco F, Brueggen J, Chène P, Drueckes P, Erdmann D, Furet P, Gerspacher M, Lang M, Ledieu D, Nolan L, Ruetz S, Trappe J, Vangrevelinghe E, Wartmann M, Wyder L, Hofmann F, Radimerski T. Potent and selective inhibition of polycythemia by the quinoxaline JAK2 inhibitor NVP-BSK805. Mol Cancer Ther. 2010 Jul;9(7):1945-55. doi: 10.1158/1535-7163.MCT-10-0053. Epub 2010 Jun 29. PMID: 20587663. 2. Kamigaki M, Hide I, Yanase Y, Shiraki H, Harada K, Tanaka Y, Seki T, Shirafuji T, Tanaka S, Hide M, Sakai N. The Toll-like receptor 4-activated neuroprotective microglia subpopulation survives via granulocyte macrophage colony-stimulating factor and JAK2/STAT5 signaling. Neurochem Int. 2016 Feb;93:82-94. doi: 10.1016/j.neuint.2016.01.003. Epub 2016 Jan 21. PMID: 26802935. 3. Hua Y, Wang W, Zheng X, Yang L, Wu H, Hu Z, Li Y, Yue J, Jiang Z, Zhang X, Hou Q, Wu S. NVP-BSK805, an Inhibitor of JAK2 Kinase, Significantly Enhances the Radiosensitivity of Esophageal Squamous Cell Carcinoma in vitro and in vivo. Drug Des Devel Ther. 2020 Feb 24;14:745-755. doi: 10.2147/DDDT.S203048. PMID: 32158193; PMCID: PMC7047839. 4. Haissaguerre M, Ferriere A, Clark S, Guzman-Quevedo O, Tabarin A, Cota D. NPV-BSK805, an Antineoplastic Jak2 Inhibitor Effective in Myeloproliferative Disorders, Causes Adiposity in Mice by Interfering With the Action of Leptin. Front Pharmacol. 2018 May 15;9:527. doi: 10.3389/fphar.2018.00527. PMID: 29867515; PMCID: PMC5962752.

In vitro protocol:

In vivo protocol:

1. Hua Y, Wang W, Zheng X, Yang L, Wu H, Hu Z, Li Y, Yue J, Jiang Z, Zhang X, Hou Q, Wu S. NVP-BSK805, an Inhibitor of JAK2 Kinase, Significantly Enhances the Radiosensitivity of Esophageal Squamous Cell Carcinoma in vitro and in vivo. Drug Des Devel Ther. 2020 Feb 24;14:745-755. doi: 10.2147/DDDT.S203048. PMID: 32158193; PMCID: PMC7047839. 2. Haissaguerre M, Ferriere A, Clark S, Guzman-Quevedo O, Tabarin A, Cota D. NPV-BSK805, an Antineoplastic Jak2 Inhibitor Effective in Myeloproliferative Disorders, Causes Adiposity in Mice by Interfering With the Action of Leptin. Front Pharmacol. 2018 May 15;9:527. doi: 10.3389/fphar.2018.00527. PMID: 29867515; PMCID: PMC5962752.

1: Baffert F, Régnier CH, De Pover A, et al. Potent and selective inhibition of polycythemia by the quinoxaline JAK2 inhibitor NVP-BSK805. Mol Cancer Ther. 2010;9(7):1945-1955. doi:10.1158/1535-7163.MCT-10-0053 2: Cheon JH, Kim KS, Yadav DK, Kim M, Kim HS, Yoon S. The JAK2 inhibitors CEP-33779 and NVP-BSK805 have high P-gp inhibitory activity and sensitize drug-resistant cancer cells to vincristine. Biochem Biophys Res Commun. 2017;490(4):1176-1182. doi:10.1016/j.bbrc.2017.06.178