PF-0477736
| Code | Size | Price |
|---|
| AG-CR1-3537-M005 | 5 mg | £75.00 |
Quantity:
| AG-CR1-3537-M010 | 10 mg | £120.00 |
Quantity:
| AG-CR1-3537-M050 | 50 mg | £400.00 |
Quantity:
Prices exclude any Taxes / VAT
Overview
Regulatory Status: RUO
Shipping:
AMBIENT
Storage:
Short Term: +4°C Long Term: -20°C
Documents
Further Information
Alternate Names/Synonyms:
PF0477736; PF-477736; PF-00477736
Appearance:
Yellow solid.
CAS:
952021-60-2
EClass:
32160000
Form (Short):
liquid
Handling Advice:
Keep cool and dry.
InChi:
InChI=1S/C22H25N7O2/c1-29-11-13(9-25-29)20-16-10-24-28-21(30)15-7-14(8-17(27-20)18(15)16)26-22(31)19(23)12-5-3-2-4-6-12/h7-12,19,27H,2-6,23H2,1H3,(H,26,31)(H,28,30)/t19-/m1/s1
InChiKey:
NDEXUOWTGYUVGA-LJQANCHMSA-N
Long Description:
Chemical. CAS: 952021-60-2. Formula: C22H25N7O2. MW: 419.5. 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.
MDL:
MFCD16038847
Molecular Formula:
C22H25N7O2
Molecular Weight:
419.5
Package Type:
Plastic Vial
Product 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.
Purity:
>95% (HPLC)
SMILES:
O=C1C2=C3C(NC(C4=CN(C)N=C4)=C3C=NN1)=CC(NC([C@H](N)C5CCCCC5)=O)=C2
Solubility Chemicals:
Soluble in DMSO (30mg/ml) or DMF (30mg/ml).
Transportation:
Non-hazardous
UNSPSC Category:
Protein Kinase Modulators
UNSPSC Number:
12352200
Use & Stability:
Stable for at least 2 years after receipt when stored at -20°C.
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)