1. Cell Cycle/DNA Damage
  2. Checkpoint Kinase (Chk)
  3. PF 477736

PF 477736 (Synonyms: PF 00477736)

Cat. No.: HY-10032 Purity: 98.07%
Handling Instructions

PF 477736 is a potent, selective ATP-competitive inhibitor of Chk1, with a Ki of 0.49 nM, 100-fold selectivity versus Chk2 (Ki, 47 nM).

For research use only. We do not sell to patients.

PF 477736 Chemical Structure

PF 477736 Chemical Structure

CAS No. : 952021-60-2

Size Stock
10 mM * 1 mL in DMSO Get quote
5 mg USD 90 Get quote
10 mg USD 156 Get quote
50 mg USD 552 Get quote

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Description

PF 477736 is a potent, selective ATP-competitive inhibitor of Chk1, with a Ki of 0.49 nM, 100-fold selectivity versus Chk2 (Ki, 47 nM).

IC50 & Target[1][2]

Chk1

0.49 nM (Ki)

Chk2

47 nM (Ki)

CDK1

9.9 μM (Ki)

In Vitro

PF 477736 (PF-00477736, 0.01-1 μM) abrogates the camptothecin-induced DNA damage checkpoint in a dose-dependent manner in CA46 cells. PF 477736 (180, 360, 540 nM) enhances gemcitabine-induced cytotoxicity in a time- and dose-dependent manner in HT29 cells as determined by cell survival assay. PF 477736 (360 nM) in combination with gemcitabine significantly decreases the phosphorylation of CDK1, consistent with checkpoint abrogation and cell entry into mitosis[1]. PF 477736 (PF-00477736) poorly inhibits CDK1 activity, with Ki of 9.9 μM[1][2].

In Vivo

PF 477736 (PF-00477736, 4-60 mg/kg, i.p.) once a day (s.i.d.) or twice a day (b.i.d.) treatment alone exhibits no antitumor activity in human colon Colo205 xenograft model. However, PF 477736 dependently enhances the antitumor activity of a MTD of gemcitabine. PF 477736 (15 and 30 mg/kg) induces histone H3 phosphorylation and DNA damage and increases apoptosis in Colo205 tumor samples from in vivo xenograft model[1].

Clinical Trial
Molecular Weight

419.48

Formula

C₂₂H₂₅N₇O₂

CAS No.

952021-60-2

SMILES

O=C([[email protected]@H](C1CCCCC1)N)NC2=CC3=C(C(C=NNC4=O)=C(N3)C5=CN(N=C5)C)C4=C2

Shipping

Room temperature in continental US; may vary elsewhere.

Storage
Powder -20°C 3 years
  4°C 2 years
In solvent -80°C 6 months
  -20°C 1 month
Solvent & Solubility
In Vitro: 

DMSO : 125 mg/mL (297.99 mM; Need ultrasonic)

Preparing
Stock Solutions
Concentration Solvent Mass 1 mg 5 mg 10 mg
1 mM 2.3839 mL 11.9195 mL 23.8390 mL
5 mM 0.4768 mL 2.3839 mL 4.7678 mL
10 mM 0.2384 mL 1.1920 mL 2.3839 mL
*Please refer to the solubility information to select the appropriate solvent.
In Vivo:
  • 1.

    Add each solvent one by one:  10% DMSO    40% PEG300    5% Tween-80    45% saline

    Solubility: ≥ 2.08 mg/mL (4.96 mM); Clear solution

  • 2.

    Add each solvent one by one:  10% DMSO    90% (20% SBE-β-CD in saline)

    Solubility: ≥ 2.08 mg/mL (4.96 mM); Clear solution

*All of the co-solvents are provided by MCE.
References
Cell Assay
[1]

HT29 or human umbilical vein endothelial cells are treated with gemcitabine (15 nM) or camptothecin (25 nM) for 16 h. PF 477736 (PF-00477736) is subsequently added at varying concentrations. At 4 to 48 h after the addition of PF 477736, the drug-containing medium is removed and cells are incubated in drug-free medium. When the vehicle-treated control cells are 90% confluent (8 days from plating), cells are harvested and counted by Coulter counter[1].

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Administration
[1]

Chemotherapy agents or PF 477736 (PF-00477736) are administered by i.p. injection when tumors are 100 to 150 mm3 in volume over the designated treatment schedules. Gemcitabine is administered over a range of doses including the maximum tolerated dose (MTD) in mice according to a once every 3 days for four treatments (q3d × 4) schedule. PF 477736 is administered over a range of doses (4-60 mg/kg) according to the q3d × 4 schedule beginning 24 h after gemcitabine. MTD of PF 477736 is determined to be 40 mg/kg considering the severity of the behavioral response on i.p. administration and body weight loss of 5% to 10%. For cytotoxic agents, MTD is the occurrence of mean body weight loss of 5% to 10%[1].

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

References

Purity: 98.07%

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Keywords:

PF 477736PF 00477736PF477736PF-477736PF00477736PF-00477736Checkpoint Kinase (Chk)Inhibitorinhibitorinhibit

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