PF-670462 2HCl


Catalog No. size PriceQuantity
M6553-2 2mg solid $111
M6553-10 10mg solid $436

Description

Cas:950912-80-8

Product Information:

PF-670462 2HCl is a potent inhibitor of the CK1 isoforms CK1ε and CK1δ (IC50 = 7.7 and 14 nM, respectively). Inhibition of CKIepsilon yields a perturbation of oscillator function that forestalls light as a zeitgeber, and they demonstrate that pharmacological tools such as PF-670462 may yield valuable insight into clock function. Casein kinase Iepsilon (CKIepsilon) is an essential component of the biological clock, phosphorylating PER proteins, and in doing so regulating their turnover and nuclear entry in oscillator cells of the suprachiasmatic nucleus (SCN).

 

Chemical Formula: C19H22Cl2FN5

 

Exact Mass: 337.1703

 

Molecular Weight: 410.3184

 

Elemental Analysis: C, 55.62; H, 5.40; Cl, 17.28; F, 4.63; N, 17.07

 

Synonym:

 

PF-670462

PF 670462

PF670462

PF-670462 HCl

PF-670462 hydrochloride

 

Chemical Name: 4-[1-Cyclohexyl-4-(4-fluorophenyl)-1H-imidazol-5-yl]-2-pyrimidinamine dihydrochloride

 

InChi Key:

PSNKGVAXBSAHCH-UHFFFAOYSA-N

 

InChi Code: InChI=1S/C19H20FN5.2ClH/c20-14-8-6-13(7-9-14)17-18(16-10-11-22-19(21)24-16)25(12-23-17)15-4-2-1-3-5-15;;/h6-12,15H,1-5H2,(H2,21,22,24);2*1H

 

Smiles Code:

NC1=NC=CC(C2=C(C3=CC=C(F)C=C3)N=CN2C4CCCCC4)=N1.[H]Cl.[H]Cl

 

 

Technical Data:

 

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: >2 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

 

In Vitro

PF-670462 is a potent and selective inhibitor of CKIε and CKIδ, with IC50s of 7.7 nM and 14 nM, respectively. PF-670462 shows less than 30-fold selevtivity for EGFR and SAPK2A/p38, with IC50s of 150 nM and 190 nM, respectively. PF-670462 also causes a redistribution of the GFP signal to the cytoplasm in a concentration-dependent manner, with an EC50 of 290 ± 39 nM in CKIε-transfected COS7 cells. PF-670462 is a potent inhibitor of Wnt/β-catenin signaling, with an IC50 of ∼17 nM. PF-670462 (1 μM) is a weak inhibitor of proliferation, and only modestly suppresses the growth of HEK293 and HT1080 cells. PF-670462 (100 nM) strongly inhibits CK1ε and CK1δ, consistent with its effect on Wnt/β-catenin signaling.

 

In Vivo

PF-670462 (50 mg/kg, s.c.) produces robust phase delays, and the activity remains persistent, with no discernible correction in the absence of exogenous zeitgebers in rats. PF-670462 (25, 50, and 100 mg/kg, s.c.) induces dose-dependent phase shift[1]. PF-670462 (50 mg/kg; s.c.) significantly phase delays the rhythmic transcription of Bmal1, Per1, Per2 and Nr1d1 in both liver and pancreas by 4.5 ± 1.3 h and 4.5 ± 1.2 h, respectively, 1 day after administration. In the suprachiasmatic nucleus (SCN), the rhythm of Nr1d1 and Dbp mRNA expression is also delayed by 4.2 and 4 h, respectively.

 

 

References

 

  1. Young EE, Bryant CD, Lee SE, Peng X, Cook B, Nair HK, Dreher KJ, Zhang X, Palmer AA, Chung JM, Mogil JS, Chesler EJ, Lariviere WR. Systems genetic and pharmacological analysis identifies candidate genes underlying mechanosensation in the von Frey test. Genes Brain Behav. 2016 Jul;15(6):604-15. doi: 10.1111/gbb.12302. PubMed PMID: 27231153.

 

  1. Solocinski K, Richards J, All S, Cheng KY, Khundmiri SJ, Gumz ML. Transcriptional regulation of NHE3 and SGLT1 by the circadian clock protein Per1 in proximal tubule cells. Am J Physiol Renal Physiol. 2015 Dec 1;309(11):F933-42. doi: 10.1152/ajprenal.00197.2014. Epub 2015 Sep 16. PubMed PMID: 26377793; PubMed Central PMCID: PMC4669359.

 

  1. Kennaway DJ, Varcoe TJ, Voultsios A, Salkeld MD, Rattanatray L, Boden MJ. Acute inhibition of casein kinase 1δ/ε rapidly delays peripheral clock gene rhythms. Mol Cell Biochem. 2015 Jan;398(1-2):195-206. doi: 10.1007/s11010-014-2219-8. Epub 2014 Sep 23. PubMed PMID: 25245819.

 

  1. 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. PubMed PMID: 24076244; PubMed Central PMCID: PMC3793863.

 

  1. van Ooijen G, Hindle M, Martin SF, Barrios-Llerena M, Sanchez F, Bouget FY, O'Neill JS, Le Bihan T, Millar AJ. Functional analysis of Casein Kinase 1 in a minimal circadian system. PLoS One. 2013 Jul 25;8(7):e70021. doi: 10.1371/journal.pone.0070021. Print 2013. PubMed PMID: 23936135; PubMed Central PMCID: PMC3723912.

 

Products are for research use only. Not for human use.

 

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