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MedKoo Cat#: 526745 | Name: PF-670462 HCl
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Description:

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

PF-670462 is a potent inhibitor of the CK1 isoforms CK1ε and CK1δ (IC50 = 7.7 and 14 nM, respectively), with applications towards treatment of bladder cancer. 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 Structure

PF-670462 HCl
PF-670462 HCl
CAS#950912-80-8 (HCl)

Theoretical Analysis

MedKoo Cat#: 526745

Name: PF-670462 HCl

CAS#: 950912-80-8 (HCl)

Chemical Formula: C19H22Cl2FN5

Exact Mass: 0.0000

Molecular Weight: 410.32

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

Price and Availability

Size Price Availability Quantity
25mg USD 450.00 2 Weeks
50mg USD 750.00 2 Weeks
100mg USD 1,250.00 2 Weeks
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Related CAS #
950980-98-0 (free base) 950912-80-8 (HCl)
Synonym
PF-670462; PF 670462; PF670462; PF-670462 HCl; PF-670462 hydrochloride.
IUPAC/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
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
More Info
Product Data
Product Data
Instruction
View handling instruction
Biological target:
PF-670462 dihydrochloride is a potent and selective inhibitor of casein kinase (CK1ε and CK1δ), with IC50s of 7.7 nM and 14 nM.
In vitro activity:
This study examined the abundance of CK1 delta and epsilon (CK1δ/ε) in lung tissue from IPF patients and non-diseased controls, and investigated whether inhibition of CK1δ/ε with PF670462 inhibits pulmonary fibrosis. In vitro, PF670462 prevented TGF-β-induced epithelial-mesenchymal transition. The stiffness of IPF-derived spheroids was reduced by PF670462 and TGF-β-induced fibrogenic gene expression was inhibited. Reference: Front Pharmacol. 2018 Jul 10;9:738. https://pubmed.ncbi.nlm.nih.gov/30042678/
In vivo activity:
The present study used PF-670462 (PF), which is a selective inhibitor of Csnk1-epsilon, to directly evaluate the role of Csnk1-epsilon in the locomotor stimulant response to MA in male C57BL/6J mice. Intraperitoneal PF (20-40 mg/kg) attenuated the locomotor stimulant response to MA (2 mg/kg) without affecting baseline activity. The high dose of PF also significantly inhibited MA-induced phosphorylation of Darpp-32, providing a potential mechanism by which Csnk1-epsilon contributes to MA-induced locomotor activity. Furthermore, microinjection of PF (5 microg/side) into the NAc completely blocked the locomotor stimulant response to MA (2.5 microg/side) without affecting baseline activity. Reference: Psychopharmacology (Berl). 2009 May;203(4):703-11. https://pubmed.ncbi.nlm.nih.gov/19050854/
Solvent mg/mL mM comments
Solubility
DMSO 43.8 106.64
Ethanol 17.5 42.65
PBS (pH 7.2) 5.0 12.19
Water 91.0 221.78
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 410.32 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.

Recalculate based on batch purity %
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. Keenan CR, Langenbach SY, Jativa F, Harris T, Li M, Chen Q, Xia Y, Gao B, Schuliga MJ, Jaffar J, Prodanovic D, Tu Y, Berhan A, Lee PVS, Westall GP, Stewart AG. Casein Kinase 1δ/ε Inhibitor, PF670462 Attenuates the Fibrogenic Effects of Transforming Growth Factor-β in Pulmonary Fibrosis. Front Pharmacol. 2018 Jul 10;9:738. doi: 10.3389/fphar.2018.00738. PMID: 30042678; PMCID: PMC6048361. 2. Badura L, Swanson T, Adamowicz W, Adams J, Cianfrogna J, Fisher K, Holland J, Kleiman R, Nelson F, Reynolds L, St Germain K, Schaeffer E, Tate B, Sprouse J. An inhibitor of casein kinase I epsilon induces phase delays in circadian rhythms under free-running and entrained conditions. J Pharmacol Exp Ther. 2007 Aug;322(2):730-8. doi: 10.1124/jpet.107.122846. Epub 2007 May 14. PMID: 17502429. 3. Sprouse J, Reynolds L, Swanson TA, Engwall M. Inhibition of casein kinase I epsilon/delta produces phase shifts in the circadian rhythms of Cynomolgus monkeys. Psychopharmacology (Berl). 2009 Jul;204(4):735-42. doi: 10.1007/s00213-009-1503-x. Epub 2009 Mar 11. PMID: 19277609. 4. Bryant CD, Graham ME, Distler MG, Munoz MB, Li D, Vezina P, Sokoloff G, Palmer AA. A role for casein kinase 1 epsilon in the locomotor stimulant response to methamphetamine. Psychopharmacology (Berl). 2009 May;203(4):703-11. doi: 10.1007/s00213-008-1417-z. Epub 2008 Dec 3. PMID: 19050854; PMCID: PMC2729782.
In vitro protocol:
1. Keenan CR, Langenbach SY, Jativa F, Harris T, Li M, Chen Q, Xia Y, Gao B, Schuliga MJ, Jaffar J, Prodanovic D, Tu Y, Berhan A, Lee PVS, Westall GP, Stewart AG. Casein Kinase 1δ/ε Inhibitor, PF670462 Attenuates the Fibrogenic Effects of Transforming Growth Factor-β in Pulmonary Fibrosis. Front Pharmacol. 2018 Jul 10;9:738. doi: 10.3389/fphar.2018.00738. PMID: 30042678; PMCID: PMC6048361. 2. Badura L, Swanson T, Adamowicz W, Adams J, Cianfrogna J, Fisher K, Holland J, Kleiman R, Nelson F, Reynolds L, St Germain K, Schaeffer E, Tate B, Sprouse J. An inhibitor of casein kinase I epsilon induces phase delays in circadian rhythms under free-running and entrained conditions. J Pharmacol Exp Ther. 2007 Aug;322(2):730-8. doi: 10.1124/jpet.107.122846. Epub 2007 May 14. PMID: 17502429.
In vivo protocol:
1. Sprouse J, Reynolds L, Swanson TA, Engwall M. Inhibition of casein kinase I epsilon/delta produces phase shifts in the circadian rhythms of Cynomolgus monkeys. Psychopharmacology (Berl). 2009 Jul;204(4):735-42. doi: 10.1007/s00213-009-1503-x. Epub 2009 Mar 11. PMID: 19277609. 2. Bryant CD, Graham ME, Distler MG, Munoz MB, Li D, Vezina P, Sokoloff G, Palmer AA. A role for casein kinase 1 epsilon in the locomotor stimulant response to methamphetamine. Psychopharmacology (Berl). 2009 May;203(4):703-11. doi: 10.1007/s00213-008-1417-z. Epub 2008 Dec 3. PMID: 19050854; PMCID: PMC2729782.
Lin YC, Chen MC, Hsieh TH, Liou JP, Chen CH. CK1δ as a potential therapeutic target to treat bladder cancer. Aging (Albany NY). 2020 Apr 13;12(7):5764-5780. doi: 10.18632/aging.102966. Epub 2020 Apr 13. PMID: 32282334; PMCID: PMC7185098. 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. 2: 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. 3: 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. 4: 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. 5: 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. 6: Kim JK, Forger DB, Marconi M, Wood D, Doran A, Wager T, Chang C, Walton KM. Modeling and validating chronic pharmacological manipulation of circadian rhythms. CPT Pharmacometrics Syst Pharmacol. 2013 Jul 17;2:e57. doi: 10.1038/psp.2013.34. PubMed PMID: 23863866; PubMed Central PMCID: PMC3734602. 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. PubMed PMID: 23349822; PubMed Central PMCID: PMC3549995. 8: Richards J, Greenlee MM, Jeffers LA, Cheng KY, Guo L, Eaton DC, Gumz ML. Inhibition of αENaC expression and ENaC activity following blockade of the circadian clock-regulatory kinases CK1δ/ε. Am J Physiol Renal Physiol. 2012 Oct;303(7):F918-27. doi: 10.1152/ajprenal.00678.2011. Epub 2012 Jul 25. PubMed PMID: 22832921; PubMed Central PMCID: PMC3469687. 9: Arey R, McClung CA. An inhibitor of casein kinase 1 ε/δ partially normalizes the manic-like behaviors of the ClockΔ19 mouse. Behav Pharmacol. 2012 Aug;23(4):392-6. doi: 10.1097/FBP.0b013e32835651fd. PubMed PMID: 22743604; PubMed Central PMCID: PMC3673712. 10: Perreau-Lenz S, Vengeliene V, Noori HR, Merlo-Pich EV, Corsi MA, Corti C, Spanagel R. Inhibition of the casein-kinase-1-ε/δ/ prevents relapse-like alcohol drinking. Neuropsychopharmacology. 2012 Aug;37(9):2121-31. doi: 10.1038/npp.2012.62. Epub 2012 May 2. PubMed PMID: 22549116; PubMed Central PMCID: PMC3398717. 11: Long A, Zhao H, Huang X. Structural basis for the interaction between casein kinase 1 delta and a potent and selective inhibitor. J Med Chem. 2012 Jan 26;55(2):956-60. doi: 10.1021/jm201387s. Epub 2012 Jan 5. PubMed PMID: 22168824. 12: Roberds SL, Filippov I, Alexandrov V, Hanania T, Brunner D. Rapid, computer vision-enabled murine screening system identifies neuropharmacological potential of two new mechanisms. Front Neurosci. 2011 Sep 9;5:103. doi: 10.3389/fnins.2011.00103. eCollection 2011. PubMed PMID: 21927596; PubMed Central PMCID: PMC3169783. 13: Li D, Herrera S, Bubula N, Nikitina E, Palmer AA, Hanck DA, Loweth JA, Vezina P. Casein kinase 1 enables nucleus accumbens amphetamine-induced locomotion by regulating AMPA receptor phosphorylation. J Neurochem. 2011 Jul;118(2):237-47. doi: 10.1111/j.1471-4159.2011.07308.x. Epub 2011 Jun 6. PubMed PMID: 21564097; PubMed Central PMCID: PMC3129449. 14: 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. PubMed PMID: 21258417; PubMed Central PMCID: PMC3109269. 15: 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. PubMed PMID: 20696890; PubMed Central PMCID: PMC2930590. 16: Sprouse J, Reynolds L, Kleiman R, Tate B, Swanson TA, Pickard GE. Chronic treatment with a selective inhibitor of casein kinase I delta/epsilon yields cumulative phase delays in circadian rhythms. Psychopharmacology (Berl). 2010 Jul;210(4):569-76. doi: 10.1007/s00213-010-1860-5. Epub 2010 Apr 21. PubMed PMID: 20407760. 17: 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. PubMed PMID: 19458106. 18: Sprouse J, Reynolds L, Swanson TA, Engwall M. Inhibition of casein kinase I epsilon/delta produces phase shifts in the circadian rhythms of Cynomolgus monkeys. Psychopharmacology (Berl). 2009 Jul;204(4):735-42. doi: 10.1007/s00213-009-1503-x. Epub 2009 Mar 11. PubMed PMID: 19277609. 19: Bryant CD, Graham ME, Distler MG, Munoz MB, Li D, Vezina P, Sokoloff G, Palmer AA. A role for casein kinase 1 epsilon in the locomotor stimulant response to methamphetamine. Psychopharmacology (Berl). 2009 May;203(4):703-11. doi: 10.1007/s00213-008-1417-z. Epub 2008 Dec 3. PubMed PMID: 19050854; PubMed Central PMCID: PMC2729782. 20: Badura L, Swanson T, Adamowicz W, Adams J, Cianfrogna J, Fisher K, Holland J, Kleiman R, Nelson F, Reynolds L, St Germain K, Schaeffer E, Tate B, Sprouse J. An inhibitor of casein kinase I epsilon induces phase delays in circadian rhythms under free-running and entrained conditions. J Pharmacol Exp Ther. 2007 Aug;322(2):730-8. Epub 2007 May 14. PubMed PMID: 17502429.