CP-654577
CP-654577 is a selective ErbB2 inhibitor with an IC50 of 11 nM. CP-654577 downregulates the Notch1 signaling pathway. CP-654577 upregulates p27kip1, reduces the levels of Cyclins D and E, and inhibits G1 phase progression of the cell cycle. CP-654577 induces cell Apoptosis, downregulates activated Akt, and suppresses tumor growth in athymic mice. CP-654577 can be used in breast cancer-related research.
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- CAS No.: 639087-64-2
- Formule: C34H32N4O3
- Masse moléculaire:544.66
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Stockage:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Activité biologique
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Chemical Information
- Pureté et documentation
- Références
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Activité biologique
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ErbB2 11 nM (IC50) |
EGFR 670 nM (IC50) |
CP-654577 (300-1000 nM) reduces Notch1 signaling (measured via CBF reporter activity) in ErbB2-overexpressing SKBR3 breast cancer cells, with 1000 nM causing a 50% reduction in activity[1].
CP-654577 (300-1000 nM; 36 hours post-transfection) does not affect Notch1 (CBF reporter) or Wnt (TOP-luc) signaling in low-ErbB2-expressing MCF-7 breast cancer cells at concentrations of 300 nM and 1000 nM[1].
CP-654577 (6 min) is a selective inhibitor of purified human erbB2 kinase, with 60-fold higher potency against erbB2 (IC50 = 11 nM) than EGFr (IC50 = 670 nM), and shows limited activity against other non-erbB family tyrosine kinases[2].
CP-654577 (0.1-3 μM; 2 h pre-incubation before 15 min EGF stimulation) selectively inhibits erbB2 kinase activity in intact NIH 3T3 cells, potently suppressing EGF-induced phosphotyrosine levels in erbB2/EGFR chimera-transfected cells (to <5% of control at ≥0.3 μM) while only weakly inhibiting EGFR-transfected cells at equivalent concentrations[2].
CP-654577 (24 h) potently inhibits the proliferation of SKBr3 human breast cancer cells with an IC50 of 55 nM after 24 h of exposure[2].
CP-654577 (50 nM-1000 nM; 2 h, 8 h, 12 h, 24 h) induces a concentration-dependent G1 cell-cycle arrest in SKBr3 human breast cancer cells, with marked effects observed at 250 nM and 1000 nM after 8 h, 12 h, and 24 h of exposure[2].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:SKBr3 human breast cancer cells
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Concentration:50 nM-1000 nM
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Incubation Time:2 h, 8 h, 12 h, 24 h
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Result:Showed no change in cell cycle phase distribution after 2 h of treatment.
Increased the G1 cell population from 62% (control) to 67% (50 nM), 67% (250 nM), and 72% (1000 nM), while decreasing the S phase population from 30% to 26%, 25%, and 22% respectively, with no change in G2/M phase after 8 h.
Increased the G1 cell population from 62% (control) to 76% (50 nM), 84% (250 nM), and 85% (1000 nM), while decreasing the S phase population from 24% to 12%, 4%, and 1% respectively, with no change in G2/M phase after 12 h.
Increased the G1 population to 67% (50 nM), 87% (250 nM), and 93% (1000 nM), while decreasing the S phase population to 27%, 8%, and 2% respectively after 24 h.
CP-654577 (12.5-50 mg/kg; i.p.; twice daily; 7 days) dose-dependently inhibits the growth of FRE-erbB2 tumor xenografts, achieving 65% growth inhibition at 50 mg/kg twice daily after 7 days of treatment[2].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:CD-1 Nu/Nu (female, 3 to 4 weeks old)[2]
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Dosage:25 mg/kg; 37.5 mg/kg; 50 mg/kg; 75 mg/kg; 100 mg/kg
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Administration:i.p.; single dose
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Result:Reduced erbB2 tyrosine phosphorylation by approximately 32% at 25 mg/kg.
Reduced erbB2 tyrosine phosphorylation by approximately 50% at 37.5 mg/kg.
Reduced erbB2 tyrosine phosphorylation by approximately 50% at 50 mg/kg.
Reduced erbB2 tyrosine phosphorylation by approximately 60% at 75 mg/kg.
Reduced erbB2 tyrosine phosphorylation by approximately 65% at 100 mg/kg.
Achieved an ED50 of 43 mg/kg for reduction of erbB2 tyrosine phosphorylation relative to vehicle controls.
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Animal Model:CD-1 Nu/Nu (female, 3 to 4 weeks old)[2]
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Dosage:12.5 mg/kg; 25 mg/kg; 50 mg/kg
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Administration:i.p.; twice daily; 7 days
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Result:Inhibited FRE-erbB2 tumor growth by 40% at 12.5 mg/kg twice daily on Day 7 post-treatment initiation.
Inhibited FRE-erbB2 tumor growth by 58% at 25 mg/kg twice daily on Day 7 post-treatment initiation.
Inhibited FRE-erbB2 tumor growth by 65% at 50 mg/kg twice daily on Day 7 post-treatment initiation.
Caused no mortality or weight loss in any treatment group.
Chemical Information
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CAS No. 639087-64-2
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Masse moléculaire 544.66
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Formule C34H32N4O3
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SMILES
C(O)[C@H]1[C@]2([C@@]1(CN(CC3=CC=C(C=C3)C4=CC=5C(NC6=CC(OC)=C(OC7=CC=CC=C7)C=C6)=NC=NC5C=C4)C2)[H])[H]
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Livraison
Room temperature in continental US; may vary elsewhere.
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Stockage
Please store the product under the recommended conditions in the Certificate of Analysis.
Pureté et documentation
Références
[1]. Lindsay J, et al. ErbB2 induces Notch1 activity and function in breast cancer cells. Clinical and translational science. 2008 Sep;1(2):107-15. [Content Brief]
[2]. Barbacci EG, et al. The biological and biochemical effects of CP-654577, a selective erbB2 kinase inhibitor, on human breast cancer cells. Cancer research. 2003 Aug 01;63(15):4450-9. [Content Brief]
[3]. Rabindran SK, et al. Antitumor activity of HKI-272, an orally active, irreversible inhibitor of the HER-2 tyrosine kinase. Cancer research. 2004 Jun 01;64(11):3958-65. [Content Brief]
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
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