PF-670462

SKU: orb1223538

Description

PF-670462 is a potent (IC50 = 7.7 ± 2.2 nM) and selective (>30-fold with respect to 42 additional kinases) inhibitor of CK1ε in isolated enzyme preparations.(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. 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.

Key Properties

• CAS Number: 950912-80-8
• MW: 410.32
• Purity: >98% (HPLC)
• Formula: C₁₉H₂₂Cl₂FN₅
• SMILES: NC1=NC=CC(C2=C(C3=CC=C(F)C=C3)N=CN2C4CCCCC4)=N1.[H]Cl.[H]Cl
• Target: Casein Kinase
• Solubility: DMSO, Ethanol: 200 mM

Bioactivity

• 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. 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.
• 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.

Storage & Handling

• Storage: Storage temperature: -20°C. Stability: ≥ 2 years
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

PF-670462 | PF 670462 | PF670462 | PF-670462 HCl | PF-670462 hydrochloride

Quick Database Links

Gene Symbol

Casein Kinase