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Chemical Structure| 950912-80-8 Chemical Structure| 950912-80-8

Structure of PF-670462 2HCl
CAS No.: 950912-80-8

Chemical Structure| 950912-80-8

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PF-670462 is a potent and selective inhibitor of CK1ε with IC50 of 7.7 ± 2.2 nM.

Synonyms: PF-670462; PF-670462 dihydrochloride; PF-670462 (hydrochloride)

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Product Details of PF-670462 2HCl

CAS No. :950912-80-8
Formula : C19H22Cl2FN5
M.W : 410.32
SMILES Code : NC1=NC=CC(C2=C(C3=CC=C(F)C=C3)N=CN2C4CCCCC4)=N1.[H]Cl.[H]Cl
Synonyms :
PF-670462; PF-670462 dihydrochloride; PF-670462 (hydrochloride)
MDL No. :MFCD12828759
InChI Key :PSNKGVAXBSAHCH-UHFFFAOYSA-N
Pubchem ID :51049607

Safety of PF-670462 2HCl

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H335
Precautionary Statements:P261-P305+P351+P338

Related Pathways of PF-670462 2HCl

DNA
Hedgehog

Isoform Comparison

Biological Activity

Target
  • CK1

    CK1δ, IC50:13 nM

    CK1ε, IC50:90 nM

In Vitro:

Cell Line
Concentration Treated Time Description References
Vipr2−/− SCN slices 1 μM PF-670462 restored circadian rhythms in Vipr2−/− SCN slices, inducing long-period, high-amplitude bioluminescence oscillations. Proc Natl Acad Sci U S A. 2010 Aug 24;107(34):15240-5.
SCN slices 1 μM PF-670462 significantly lengthened the circadian period in SCN slices and eventually led to arrhythmia. Proc Natl Acad Sci U S A. 2010 Aug 24;107(34):15240-5.
lung fibroblasts 1 μM PF-670462 significantly lengthened the circadian period in WT, Ck1εtau, and Ck1ε−/− derived lung fibroblasts. Proc Natl Acad Sci U S A. 2010 Aug 24;107(34):15240-5.
BEAS-2B cells 1 μM and 10 μM 30 min PF-670462 dose-dependently prevented TGF-β1-induced E-cadherin loss and collagen I gain, indicating that δ- and ε-isoforms of casein kinase I and AKAPs distinctly regulate the TGF-β1-induced EMT in BEAS-2B cells. Cells. 2020 Feb 3;9(2):356.
HT1080 cells 1 µM 7 days PF-670462 only modestly reduced cell growth and did not induce cell cycle arrest or apoptosis Oncogene. 2011 Jun 2;30(22):2558-69.
HEK293 cells 1 µM 7 days PF-670462 only modestly reduced cell growth and did not induce cell cycle arrest or apoptosis Oncogene. 2011 Jun 2;30(22):2558-69.

In Vivo:

Species
Animal Model
Administration Dosage Frequency Description References
Mice CD-1 mice Intraperitoneal injection 25 µM Single injection, lasting 24 hours To evaluate the protective effect of PF-670462 on CDDP-induced oocyte apoptosis. PF-670462 effectively blocked cisplatin-induced oocyte death, indicating that CK1-mediated phosphorylation is essential for TAp63 αactivation, even in the absence of tetramer formation. Cell Death Dis. 2024 Nov 7;15(11):799.
Mice WT, Ck1εtau, and Ck1ε−/− mice Intraperitoneal injection 10 mg/kg Daily injections for 24 days PF-670462 significantly lengthened the period of behavioral rhythms in WT, Ck1εtau, and Ck1ε?/? mice, with dose-dependent effects. Proc Natl Acad Sci U S A. 2010 Aug 24;107(34):15240-5.
Rats Alcohol Deprivation Effect model Intraperitoneal injection 0, 10, and 30 mg/kg Every 12 hours, total of 5 injections PF-670462 dose-dependently decreased and prevented the alcohol deprivation effect, with the higher dosage completely preventing the alcohol deprivation effect. Neuropsychopharmacology. 2012 Aug;37(9):2121-31
Mice DSS-induced ulcerative colitis model Subcutaneous injection 50 mg/kg Once daily, throughout the experiment PF-670462 inhibited the deterioration of DSS-induced ulcerative colitis caused by UVB eye irradiation. Int J Biol Sci. 2018 Jun 2;14(9):992-999

Protocol

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