GLPBio

PF-477736

Catalog No.: GC14234Purity:>99.00%Synonyms: PF 00477736
COASDSData Sheet
PF-477736 (PF 00477736) ist ein potenter, selektiver und ATP-kompetitiver Inhibitor von Chk1 mit einem Ki von 0,49 nM, es ist auch ein Chk2-Inhibitor mit einem Ki von 47 nM. PF-477736 zeigt eine \u003c100-fache Selektivität für Chk1 gegenüber VEGFR2, Fms, Yes, Aurora-A, FGFR3, Flt3 und Ret (IC50\u003d8 (Ki), 10, 14, 23, 23, 25 und 39 nM, beziehungsweise). PF-477736 kann die Antitumoraktivität von Gemcitabin in vitro und in vivo verstärken.

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PF-477736
Cas No.: 952021-60-2
10mM (in 1mL DMSO)In Stock
$91.00
1
1mgIn Stock
$31.00
1
5mgIn Stock
$83.00
1
10mgIn Stock
$144.00
1
50mgIn Stock
$468.00
1
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    641, 529–536 (2025)
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    628, 630–638 (2024)
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    Nature
    632, 686–694 (2024)
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    Nature
    618, 1017–1023 (2023)
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    Nature
    610, 366–372 (2022)
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    Cell
    187(9):2288-2304 (2024)
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    Cell
    183(7):1867-1883 (2020)
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    388(6745) (2025)
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    387(6734) (2025)
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    35, 97–116 (2025)
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    34, 683–706 (2024)
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    33, 273–287 (2023)
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    33, 546–561 (2023)
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    33, 904–922 (2023)
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    Cell Research
    31, 1291–1307 (2021)

Beschreibung (Description)

PF-477736 is a potent, selective ATP-competitive and small-molecule inhibitor of Chk1 with a Ki of 0.49±0.29nM for the in vitro kinase activity of Chk1 [1].

PF-477736 has shown a selective inhibition of Chk1 with the IC50 values of 0.49nM, 9.9μM and 47nM for Chk1, CDK1 and Chk2, respectively. In a dot-blot assay, PF-477736 has been reported to inhibit camptothecin-induced G2 arrest with the EC50 values of 45nM, 38nM and 42nM in P53-mutated human lymphoma CA46 cells, HeLa cells and HT29 cells. Apart from these, PF-477736 has been found to selectively target p53-defective cancer cells while having minimal cytotoxic effects on normal (p53-competent) cells. In addition, PF-00477736 has been revealed to dose-dependently enhance the antitumor activity of a MTD of gemcitabine with no apparent exacerbation of systemic toxicity as assessed by monitoring body weight in the Colo205 xenograft [1].

References:
[1] Blasina A1, Hallin J, Chen E, Arango ME, Kraynov E, Register J, Grant S, Ninkovic S, Chen P, Nichols T, O'Connor P, Anderes K. Breaching the DNA damage checkpoint via PF-00477736, a novel small-molecule inhibitor of checkpoint kinase 1. Mol Cancer Ther. 2008 Aug;7(8):2394-404.

Protokoll (Protocol)

Kinase experiment [1]:

Kinase assays

CHK1 activity was measured by a pyruvate kinase-lactate dehydrogenase coupled, continuous spectrophotometric assay method where the phosphorylation of a CHK1 peptide substrate (Syntide-2, PLARTLSVAGLPGKK) was coupled to the oxidation of NADH and the corresponding change in absorbance intensity was measured at 340 nm. The assay was performed in a 96-well plate for 20 minutes at 30°C in 0.1 mL of assay buffer containing 50 mM TRIS pH 7.5, 0.4 M NaCl, 4 mM PEP, 0.15 mM NADH, 28 units of lactate dehydrogenase/mL, 16 units of pyruvate kinase/mL, 3 mM DTT, 0.125 mM Syntide-2, 0.15 mM ATP and 25 mM magnesium chloride. Assays were initiated with 1nM of CHK1 kinase domain. The inhibition of CHK1 activity was determined by measuring initial velocities in the presence of varying concentrations of PF-477736.
Cell experiment [2]:

Cell lines

HT29 cell lines

Preparation method

The solubility of this compound in DMSO is >5.2mg/mL. General tips for obtaining a higher concentration: Please warm the tube at 37℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months.

Reacting condition

69 nM, 24h

Applications

The gemcitabine and PF-477736 combination induced significant potentiation of the cytotoxic activity of gemcitabine, indicating that the combination treatment caused a permanent cellular damage that cannot be overcome even after drug removal. The cell kill induced by the combination treatment is time and dose dependent.
Animal experiment [2]:

Animal models

Colo205 Xenograft Models in Athymic Nude Mice

Dosage form

i.p., 4-60 mg/kg，q3d × 4

Application

In xenografts, PF-477736 enhanced the antitumor activity of gemcitabine in a dose-dependent manner.

Other notes

Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal.

References:

[1] Blasina A1, Hallin J, Chen E, Arango ME, Kraynov E, Register J, Grant S, Ninkovic S, Chen P, Nichols T, O'Connor P, Anderes K. Breaching the DNA damage checkpoint via PF-00477736, a novel small-molecule inhibitor of checkpoint kinase 1. Mol Cancer Ther. 2008 Aug;7(8):2394-404.

Produktdokumente (Product Documents)

Purity:>99.00%Appearance:A solid
COASDSData Sheet

Chemische Eigenschaften (Chemical Properties)

CAS-Nr.
952021-60-2
Synonyme
PF 00477736
Chemischer Name
(R)-2-amino-2-cyclohexyl-N-(2-(1-methyl-1H-pyrazol-4-yl)-6-oxo-5,6-dihydro-4H-[1,2]diazepino[4,5,6-cd]indol-8-yl)acetamide
SMILES
O=C(C(C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C1([H])[H])([H])N([H])[H])N([H])C2=C([H])C3=C4C(N=C(C5=C([H])N(C([H])([H])[H])N=C5[H])C4=C([H])N([H])N([H])C3=O)=C2[H]
Summenformel
C22H25N7O2
Molekulargewicht
419.48
Löslichkeit
≥ 5.2mg/mL in DMSO
Lagerung
Store at -20°C
Allgemeine Hinweise
Wählen Sie anhand der Löslichkeitsdaten des Produkts ein geeignetes Lösungsmittel. Aliquotieren Sie die Stammlösung nach der Herstellung, um wiederholte Gefrier-Auftau-Zyklen zu vermeiden.
Verwenden Sie Stammlösungen bei Lagerung bei -80°C innerhalb von 6 Monaten bzw. bei -20°C innerhalb von 1 Monat.
Zur Verbesserung der Löslichkeit das Röhrchen auf 37°C erwärmen und für eine angemessene Dauer beschallen.
Versandbedingungen
Evaluierungsmuster werden mit Kühlakkus versandt. Andere verfügbare Größen werden bei Raumtemperatur oder auf Anfrage mit Kühlakkus versandt.

Rechner (Calculators)Molarität / Verdünnung / Molekulargewicht / Einheitenumrechnung / In-vivo-Formulierung / Löslichkeit

g/mol

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