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AdipoGen Life Sciences
PF-0477736
80
CHF
CHF 80.00
In stock
AG-CR1-3537-M0055 mgCHF 80.00
AG-CR1-3537-M01010 mgCHF 130.00
AG-CR1-3537-M05050 mgCHF 460.00
| Product Details | |
|---|---|
| Synonyms | PF0477736; PF-477736; PF-00477736 |
| Product Type | Chemical |
| Properties | |
| Formula |
C22H25N7O2 |
| MW | 419.5 |
| CAS | 952021-60-2 |
| Purity Chemicals | ≥95% (HPLC) |
| Appearance | Yellow solid. |
| Solubility | Soluble in DMSO (30mg/ml) or DMF (30mg/ml). |
| Identity | Determined by 1H-NMR. |
| InChi Key | NDEXUOWTGYUVGA-LJQANCHMSA-N |
| Smiles | O=C1C2=C3C(NC(C4=CN(C)N=C4)=C3C=NN1)=CC(NC([C@H](N)C5CCCCC5)=O)=C2 |
| Shipping and Handling | |
| Shipping | AMBIENT |
| Short Term Storage | +4°C |
| Long Term Storage | -20°C |
| Handling Advice | Keep cool and dry. |
| Use/Stability | Stable for at least 2 years after receipt when stored at -20°C. |
| Documents | |
| MSDS |
 Download PDF |
| Product Specification Sheet | |
| Datasheet |
Download PDF |
Description
- PF-0477736 is a potent, selective ATP-competitive inhibitor of Chk1 (Ki = 0.49nM) with 100-fold selectivity over Chk2 (Ki = 47nM). When used in combination with various chemotherapeutics (e.g. gemcitabine and carboplatin), PF-0477736 abrogates DNA damage-induced cell cycle arrest, sensitizes cells to DNA damage, potentiating the antiproliferative effects of these compounds in vitro and in vivo in tumor cell lines and xenografts.
- PF-0477736 shows <100-fold selectivity for Chk1 over VEGFR2, Fms, Yes, Aurora-A, FGFR3, Flt3 and Ret (Ki = 10, 14, 23, 23, 25 and 39 nM, respectively).
- Checkpoint kinase 1 (Chk1) belongs to the Ca2+/calmodulin-dependent protein kinase class of enzymes (CAMK). CAMKs are activated by increases in the concentration of intracellular calcium ions (Ca2+) and calmodulin. When activated, the CAMKs transfer phosphates from ATP to defined serine or threonine residues in other proteins, therefore CAMKs are serine/threonine-specific protein kinases. Chk1 regulates S and G2-M phase cell cycle checkpoints in response to DNA damage. Antagonizing the Chk1-mediated cell cycle checkpoints has emerged as an attractive target for anticancer therapy. If Chk1 activity is blocked, DNA-damaged or spindle-disrupted cells would exit cell cycle arrest before full repair and subsequently undergo mitotic catastrophe or cell death. Chk1 inhibitors consequently increase the therapeutic index of DNA-damaging or antimitotic agents as well.
Product References
- Breaching the DNA damage checkpoint via PF-00477736, a novel small-molecule inhibitor of checkpoint kinase 1: A. Blasina, et al.; Mol. Cancer Ther. 7, 2394 (2008)
- DNA damage detection and repair pathways-recent advances with inhibitors of checkpoint kinases in cancer therapy: S. Ashwell & S. Zabludoff; Clin. Cancer Res. 14, 4032 (2008)
- PF-00477736 mediates checkpoint kinase 1 signaling pathway and potentiates docetaxel-induced efficacy in xenografts: C. Zhang, et al.; Clin. Cancer Res. 15, 4630 (2009)
- In vitro and in vivo single-agent efficacy of checkpoint kinase inhibition in acute lymphoblastic leukemia: I. Iacobucci, et al.; J. Hematol. Oncol. 8, 125 (2015)
- Constitutive activation of the DNA damage response pathway as a novel therapeutic target in diffuse large B-cell lymphoma: E. Derenzini, et al.; Oncotarget 6, 6553 (2015)
- Synergism between bosutinib (SKI-606) and the Chk1 inhibitor (PF-00477736) in highly imatinib-resistant BCR/ABL+ leukemia cells: T. Nguyen, et al.; Leuk. Res. 39, 65 (2015)
- CEP131 Abrogates CHK1 Inhibitor-Induced Replication Defects and Is Associated with Unfavorable Outcome in Neuroblastoma: K. Ando, et al.; J. Oncol. 2020, 2752417 (2020)
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