PF 477736
Based on 4 publication(s) in Google Scholar
PF 477736 (PF 00477736) is a potent, selective and ATP-competitive inhibitor of Chk1, with a Ki of 0.49 nM, it is also a Chk2 inhibitor, with a Ki of 47 nM. PF 477736 shows <100-fold selectivity for Chk1 over VEGFR2, Fms, Yes, Aurora-A, FGFR3, Flt3, and Ret (IC50=8 (Ki), 10, 14, 23, 23, 25, and 39 nM, respectively). PF 477736 can enhance Gemcitabine antitumor activity in vitro and in vivo.
For research use only. We do not sell to patients.
- Purity: 99.04%
- CAS No.: 952021-60-2
- Formula: C22H25N7O2
- Molecular Weight:419.48
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Storage:Powder -20°C, 3 years , 4°C, 2 years ; In solvent -80°C, 6 months , -20°C, 1 month
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Biological Activity
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Chemical Information
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Solvent & Solubility
- Purity & Documentation
- References
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Help & FAQs
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Publications Citing Use of MedChemExpress (MCE) PF 477736
MoreAll VEGFR Isoforms
MoreAll Aurora Kinase Isoforms
More
Biological Activity
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Chk1 0.49 nM (Ki) |
Chk2 47 nM (Ki) |
VEGFR2 8 nM (Ki) |
Fms 10 nM (IC50) |
Yes 14 nM (IC50) |
Aurora-A 23 nM (IC50) |
FGFR3 23 nM (IC50) |
Flt3 25 nM (IC50) |
Ret 39 nM (IC50) |
CDK1 9.9 μM (Ki) |
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Cell Line
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Type | Value | Description | References |
|---|---|---|---|---|
| CA46 | EC50 |
45 nM
Compound: PF-0047736
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Inhibition of camptothecin induced DNA damage in mutated human CA46 cells assessed as increase in mitotic index by measuring histone H3 phosphorylation at S10 residue at 0.001 to 1 uM measured after 16 hrs presence of nocodazole by dot blot assay
Inhibition of camptothecin induced DNA damage in mutated human CA46 cells assessed as increase in mitotic index by measuring histone H3 phosphorylation at S10 residue at 0.001 to 1 uM measured after 16 hrs presence of nocodazole by dot blot assay
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[PMID: 18723486] |
| COLO 205 | IC50 |
1.3 μM
Compound: PF-0047736
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Antiproliferative activity against human COLO 205 cells deficit of p53 expression assessed as inhibition of cell growth measured after 96 hrs by MTT assay
Antiproliferative activity against human COLO 205 cells deficit of p53 expression assessed as inhibition of cell growth measured after 96 hrs by MTT assay
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[PMID: 18723486] |
| HeLa | EC50 |
38 nM
Compound: PF-0047736
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Inhibition of camptothecin induced DNA damage in human HeLa cells assessed as increase in mitotic index by measuring histone H3 phosphorylation at S10 residue at 0.001 to 1 uM measured after 16 hrs presence of nocodazole by dot blot assay
Inhibition of camptothecin induced DNA damage in human HeLa cells assessed as increase in mitotic index by measuring histone H3 phosphorylation at S10 residue at 0.001 to 1 uM measured after 16 hrs presence of nocodazole by dot blot assay
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[PMID: 18723486] |
| HT-29 | EC50 |
42 nM
Compound: PF-0047736
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Inhibition of camptothecin induced DNA damage in human HT-29 cells assessed as increase in mitotic index by measuring histone H3 phosphorylation at S10 residue at 0.001 to 1 uM measured after 16 hrs presence of nocodazole by dot blot assay
Inhibition of camptothecin induced DNA damage in human HT-29 cells assessed as increase in mitotic index by measuring histone H3 phosphorylation at S10 residue at 0.001 to 1 uM measured after 16 hrs presence of nocodazole by dot blot assay
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[PMID: 18723486] |
| HT-29 | IC50 |
1.8 μM
Compound: PF-0047736
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Antiproliferative activity against human HT-29 cells deficit of p53 expression assessed as inhibition of cell growth measured after 96 hrs by MTT assay
Antiproliferative activity against human HT-29 cells deficit of p53 expression assessed as inhibition of cell growth measured after 96 hrs by MTT assay
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[PMID: 18723486] |
| K562 | IC50 |
0.42 μM
Compound: PF-0047736
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Antiproliferative activity against human K562 cells deficit of p53 expression assessed as inhibition of cell growth measured after 96 hrs by MTT assay
Antiproliferative activity against human K562 cells deficit of p53 expression assessed as inhibition of cell growth measured after 96 hrs by MTT assay
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[PMID: 18723486] |
| MDA-MB-231 | IC50 |
1.4 μM
Compound: PF-0047736
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Antiproliferative activity against human MDA-MB-231 cells deficit of p53 expression assessed as inhibition of cell growth measured after 96 hrs by MTT assay
Antiproliferative activity against human MDA-MB-231 cells deficit of p53 expression assessed as inhibition of cell growth measured after 96 hrs by MTT assay
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[PMID: 18723486] |
| PC-3 | IC50 |
1.6 μM
Compound: PF-0047736
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Antiproliferative activity against human PC-3 cells deficit of p53 expression assessed as inhibition of cell growth measured after 96 hrs by MTT assay
Antiproliferative activity against human PC-3 cells deficit of p53 expression assessed as inhibition of cell growth measured after 96 hrs by MTT assay
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[PMID: 18723486] |
PF 477736 is a poor inhibitor of CDK1 activity (Ki=9.9 μM, 20,000-fold versus Chk1)[1].
PF 477736 (0.01-1 μM; 16 h) dose-dependently abrogates the camptothecin-induced DNA damage checkpoint in CA46 cells[1].
PF 477736 (10-48 h) abrogates the Gemcitabine-induced S-phase arrest and induces increase in apoptotic cell death in HT29 cells[1].
PF 477736 (180-540 nM; 4-48 h) enhances Gemcitabine cytotoxicity in dose- and time-dependent manner in HT29 cells[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
PF 477736 (15 and 30 mg/kg; i.p.) induces histone H3 phosphorylation and DNA damage and increases apoptosis in vivo[1].
PF 477736 (4 mg/kg; i.v.) exhibits low systemic plasma clearance (11.8 mL/min/kg) and terminal half-life (2.9 h) in rats[1].
PF 477736 (4-40 mg/kg; i.p.) exhibits a dose dependent pharmacokinetics[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
| NCT Number | Sponsor | Condition | Start Date |
Phase
|
|---|---|---|---|---|
| NCT01329991 | Plexxikon| | 2011-05 | PHASE1 |
Chemical Information
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CAS No. 952021-60-2
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Appearance Solid
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Molecular Weight 419.48
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Formula C22H25N7O2
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Color Off-white to yellow
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SMILES
O=C([C@@H](C1CCCCC1)N)NC2=CC3=C(C(C=NNC4=O)=C(N3)C5=CN(N=C5)C)C4=C2
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Synonyms
PF 00477736
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Publications (4)
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Journal Impact Factor
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Most Recent
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Science
2017 Dec 1;358(6367):eaan4368. PMID: 29191878 -
Sci Transl Med
PP2A inhibition is a druggable MEK inhibitor resistance mechanism in KRAS-mutant lung cancer cells. [Abstract]2018 Jul 18;10(450):eaaq1093. PMID: 30021885 -
Cancers
2019 Oct 25;11(11):1654. PMID: 31717700 -
Solvent & Solubility
DMSO : 100 mg/mL (238.39 mM; ultrasonic and warming and heat to 60°C; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
Select the appropriate dissolution method based on your experimental animal and administration route.
- For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
- To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for In Vivo experiments, it is recommended to prepare freshly and use it on the same day.
- The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.
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
This protocol yields a clear solution of ≥ 2.08 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (20.8 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.
Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
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
This protocol yields a clear solution of ≥ 2.08 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (20.8 mg/mL) to 900 μL 20% SBE-β-CD in Saline, and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C, storage for one week): 2 g SBE-β-CD powder is dissolved in 10 mL Saline, completely dissolve until clear.
Please enter the basic information of animal experiments:
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Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Please enter your animal formula composition:
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%DMSO +
Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
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%+
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+%Tween-80 + +
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%Saline +
The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).
Working solution concentration: 0.22 mg/mL
Method for preparing stock solution: mg drug dissolved in μL DMSO. Stock solution concentration: mg/mL.
1. Take μL DMSO stock solution;
2. Add μL .
μL , mix evenly;
3. Then add μL Tween 80, mix evenly;
4. Then add μL
Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.
Purity & Documentation
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Data Sheet (280 KB)
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SDS (396 KB)
- English - EN (396 KB)
- Français - FR (396 KB)
- Deutsch - DE (396 KB)
- Norwegian - NO (396 KB)
- Español - ES (396 KB)
- Swedish - SV (396 KB)
- Italian - IT (396 KB)
- Portuguese - PT (396 KB)
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Handling Instructions (2659 KB)
References
[1]. Blasina A, et al. 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 [Content Brief]
[2]. Ashwell S, et, al. DNA damage detection and repair pathways--recent advances with inhibitors of checkpoint kinases in cancer therapy. Clin Cancer Res. 2008 Jul 1; 14(13): 4032-7. [Content Brief]
Complete Stock Solution Preparation Table
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
| Optional Solvent | Concentration Solvent Mass | 1 mg | 5 mg | 10 mg | 25 mg |
|---|---|---|---|---|---|
| DMSO | 1 mM | 2.3839 mL | 11.9195 mL | 23.8390 mL | 59.5976 mL |
| 5 mM | 0.4768 mL | 2.3839 mL | 4.7678 mL | 11.9195 mL | |
| 10 mM | 0.2384 mL | 1.1920 mL | 2.3839 mL | 5.9598 mL | |
| 15 mM | 0.1589 mL | 0.7946 mL | 1.5893 mL | 3.9732 mL | |
| 20 mM | 0.1192 mL | 0.5960 mL | 1.1920 mL | 2.9799 mL | |
| 25 mM | 0.0954 mL | 0.4768 mL | 0.9536 mL | 2.3839 mL | |
| 30 mM | 0.0795 mL | 0.3973 mL | 0.7946 mL | 1.9866 mL | |
| 40 mM | 0.0596 mL | 0.2980 mL | 0.5960 mL | 1.4899 mL | |
| 50 mM | 0.0477 mL | 0.2384 mL | 0.4768 mL | 1.1920 mL | |
| 60 mM | 0.0397 mL | 0.1987 mL | 0.3973 mL | 0.9933 mL | |
| 80 mM | 0.0298 mL | 0.1490 mL | 0.2980 mL | 0.7450 mL | |
| 100 mM | 0.0238 mL | 0.1192 mL | 0.2384 mL | 0.5960 mL |
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