PF-4800567 hydrochloride | CAS#1391052-28-0

MedKoo Cat#: 531335 | Name: PF-4800567 hydrochloride

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Description:

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

PF-4800567 is a selective inhibitor of casein kinase 1ε (CK1ε; IC50 = 32 nM) with greater than 20-fold selectivity over CK1δ. PF4800567 significantly increased the amplitude of NMDAR-EPSCs and puff NMDA currents in PVN neurons in WKY rats but not in SHRs. PF4800567 caused an NMDAR-dependent increase in the excitability of PVN neurons only in WKY rats. Also, the CK1ε protein level in the PVN was significantly lower in SHRs than in WKY rats. Furthermore, intracerebroventricular infusion of PF4800567 increased blood pressure and lumbar sympathetic nerve activity in WKY rats, and this effect was eliminated by microinjection of the NMDAR antagonist into the PVN.

Chemical Structure

PF-4800567 hydrochloride

CAS#1391052-28-0 (HCl)

Theoretical Analysis

MedKoo Cat#: 531335

Name: PF-4800567 hydrochloride

CAS#: 1391052-28-0 (HCl)

Chemical Formula: C17H19Cl2N5O2

Exact Mass: 395.0916

Molecular Weight: 396.27

Elemental Analysis: C, 51.53; H, 4.83; Cl, 17.89; N, 17.67; O, 8.07

Price and Availability

Size	Price	Availability	Quantity
5mg	USD 450.00
25mg	USD 880.00

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Related CAS #

1188296-52-7 (free base) 1391052-28-0 (HCl)

Synonym

PF-4800567 hydrochloride; PF-4800567; PF 4800567; PF4800567;

IUPAC/Chemical Name

3-[(3-Chlorophenoxy)methyl]-1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine hydrochloride

InChi Key

QZXZQMUZEHTFHD-UHFFFAOYSA-N

InChi Code

InChI=1S/C17H18ClN5O2.ClH/c18-11-2-1-3-13(8-11)25-9-14-15-16(19)20-10-21-17(15)23(22-14)12-4-6-24-7-5-12;/h1-3,8,10,12H,4-7,9H2,(H2,19,20,21);1H

SMILES Code

NC1=C2C(N(C3CCOCC3)N=C2COC4=CC=CC(Cl)=C4)=NC=N1.[H]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:

PF-4800567 hydrochloride is a casein kinase 1e (CK1e) selective inhibitor (IC50 = 32 nM) that is 20 fold selective for the CK1e isoform over CK1d.

In vitro activity:

To test this, this study characterized 3-(3-chloro-phenoxymethyl)-1-(tetrahydro-pyran-4-yl)-1H-pyrazolo[3,4-d]pyrimidin-4-ylamine (PF-4800567), a novel and potent inhibitor of CK1epsilon (IC(50) = 32 nM) with greater than 20-fold selectivity over CK1delta. PF-4800567 completely blocks CK1epsilon-mediated PER3 nuclear localization and PER2 degradation. Reference: J Pharmacol Exp Ther. 2009 Aug;330(2):430-9. https://pubmed.ncbi.nlm.nih.gov/19458106/

In vivo activity:

TBD

	Solvent	mg/mL	mM	comments
Solubility
	DMSO	39.6	100.00

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 396.27 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:

Walton KM, Fisher K, Rubitski D, Marconi M, Meng QJ, Sládek M, Adams J, Bass M, Chandrasekaran R, Butler T, Griffor M, Rajamohan F, Serpa M, Chen Y, Claffey M, Hastings M, Loudon A, Maywood E, Ohren J, Doran A, Wager TT. Selective inhibition of casein kinase 1 epsilon minimally alters circadian clock period. J Pharmacol Exp Ther. 2009 Aug;330(2):430-9. doi: 10.1124/jpet.109.151415. Epub 2009 May 19. PMID: 19458106.

In vitro protocol:

In vivo protocol:

TBD

1: Varghese RT, Young S, Pham L, Liang Y, Pridham KJ, Guo S, Murphy S, Kelly DF, Sheng Z. Casein Kinase 1 Epsilon Regulates Glioblastoma Cell Survival. Sci Rep. 2018 Sep 11;8(1):13621. doi: 10.1038/s41598-018-31864-x. PMID: 30206363; PMCID: PMC6134061. 2: Jayakumar AR, Tong XY, Shamaladevi N, Barcelona S, Gaidosh G, Agarwal A, Norenberg MD. Defective synthesis and release of astrocytic thrombospondin-1 mediates the neuronal TDP-43 proteinopathy, resulting in defects in neuronal integrity associated with chronic traumatic encephalopathy: in vitro studies. J Neurochem. 2017 Feb;140(4):645-661. doi: 10.1111/jnc.13867. Epub 2017 Jan 10. PMID: 27735996. 3: Patton AP, Chesham JE, Hastings MH. Combined Pharmacological and Genetic Manipulations Unlock Unprecedented Temporal Elasticity and Reveal Phase-Specific Modulation of the Molecular Circadian Clock of the Mouse Suprachiasmatic Nucleus. J Neurosci. 2016 Sep 7;36(36):9326-41. doi: 10.1523/JNEUROSCI.0958-16.2016. PMID: 27605609; PMCID: PMC5013184. 4: He TY, Wu DW, Lin PL, Wang L, Huang CC, Chou MC, Lee H. DDX3 promotes tumor invasion in colorectal cancer via the CK1ε/Dvl2 axis. Sci Rep. 2016 Feb 19;6:21483. doi: 10.1038/srep21483. PMID: 26892600; PMCID: PMC4759588. 5: Li DP, Zhou JJ, Pan HL. Endogenous casein kinase-1 modulates NMDA receptor activity of hypothalamic presympathetic neurons and sympathetic outflow in hypertension. J Physiol. 2015 Oct 1;593(19):4439-52. doi: 10.1113/JP270831. Epub 2015 Aug 18. PMID: 26174743; PMCID: PMC4594242. 6: Zhang L, Hastings MH, Green EW, Tauber E, Sladek M, Webster SG, Kyriacou CP, Wilcockson DC. Dissociation of circadian and circatidal timekeeping in the marine crustacean Eurydice pulchra. Curr Biol. 2013 Oct 7;23(19):1863-73. doi: 10.1016/j.cub.2013.08.038. Epub 2013 Sep 26. PMID: 24076244; PMCID: PMC3793863. 7: Smadja Storz S, Tovin A, Mracek P, Alon S, Foulkes NS, Gothilf Y. Casein kinase 1δ activity: a key element in the zebrafish circadian timing system. PLoS One. 2013;8(1):e54189. doi: 10.1371/journal.pone.0054189. Epub 2013 Jan 21. PMID: 23349822; PMCID: PMC3549995. 8: Long AM, Zhao H, Huang X. Structural basis for the potent and selective inhibition of casein kinase 1 epsilon. J Med Chem. 2012 Nov 26;55(22):10307-11. doi: 10.1021/jm301336n. Epub 2012 Nov 9. PMID: 23106386. 9: Bryant CD, Parker CC, Zhou L, Olker C, Chandrasekaran RY, Wager TT, Bolivar VJ, Loudon AS, Vitaterna MH, Turek FW, Palmer AA. Csnk1e is a genetic regulator of sensitivity to psychostimulants and opioids. Neuropsychopharmacology. 2012 Mar;37(4):1026-35. doi: 10.1038/npp.2011.287. Epub 2011 Nov 16. PMID: 22089318; PMCID: PMC3280656. 10: Cheong JK, Nguyen TH, Wang H, Tan P, Voorhoeve PM, Lee SH, Virshup DM. IC261 induces cell cycle arrest and apoptosis of human cancer cells via CK1δ/ɛ and Wnt/β-catenin independent inhibition of mitotic spindle formation. Oncogene. 2011 Jun 2;30(22):2558-69. doi: 10.1038/onc.2010.627. Epub 2011 Jan 24. PMID: 21258417; PMCID: PMC3109269. 11: Meng QJ, Maywood ES, Bechtold DA, Lu WQ, Li J, Gibbs JE, Dupré SM, Chesham JE, Rajamohan F, Knafels J, Sneed B, Zawadzke LE, Ohren JF, Walton KM, Wager TT, Hastings MH, Loudon AS. Entrainment of disrupted circadian behavior through inhibition of casein kinase 1 (CK1) enzymes. Proc Natl Acad Sci U S A. 2010 Aug 24;107(34):15240-5. doi: 10.1073/pnas.1005101107. Epub 2010 Aug 9. PMID: 20696890; PMCID: PMC2930590. 12: Walton KM, Fisher K, Rubitski D, Marconi M, Meng QJ, Sládek M, Adams J, Bass M, Chandrasekaran R, Butler T, Griffor M, Rajamohan F, Serpa M, Chen Y, Claffey M, Hastings M, Loudon A, Maywood E, Ohren J, Doran A, Wager TT. Selective inhibition of casein kinase 1 epsilon minimally alters circadian clock period. J Pharmacol Exp Ther. 2009 Aug;330(2):430-9. doi: 10.1124/jpet.109.151415. Epub 2009 May 19. PMID: 19458106.