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Chemical Structure| 952021-60-2 Chemical Structure| 952021-60-2

Structure of PF-477736
CAS No.: 952021-60-2

Chemical Structure| 952021-60-2

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PF-477736 is a selective, potent and ATP-competitive Chk1 inhibitor with Ki of 0.49 nM and also inhibits VEGFR2, Aurora-A, FGFR3, Flt3, Fms (CSF1R), Ret and Yes and shows ~100-fold selectivity for Chk1 than Chk2.

Synonyms: PF-00477736; PF-736; PF 00477736

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Product Details of PF-477736

CAS No. :952021-60-2
Formula : C22H25N7O2
M.W : 419.48
SMILES Code : O=C(NC1=CC2=C(C3=C1)C(C=NNC3=O)=C(C4=CN(C)N=C4)N2)[C@H](N)C5CCCCC5
Synonyms :
PF-00477736; PF-736; PF 00477736
MDL No. :MFCD16038847
InChI Key :NDEXUOWTGYUVGA-LJQANCHMSA-N
Pubchem ID :135565545

Safety of PF-477736

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H335
Precautionary Statements:P261-P305+P351+P338

Isoform Comparison

Biological Activity

Target
  • Chk1

    Chk1, Ki:0.49 nM

In Vitro:

Cell Line
Concentration Treated Time Description References
SKOV3 CR 20 μM 3 days To investigate the combined effect of PF-477736 with cisplatin on cell viability. PMC7474466
HRP UWB+B1 cells 50 nM 24 hours PF-477736 inhibited rucaparib-induced CHK1S296 phosphorylation and reduced RAD51 foci formation, indicating inhibition of HRR function. PMC11369084
HRP V-C8.B2 cells 50 nM 24 hours PF-477736 significantly potentiated rucaparib cytotoxicity, indicating sensitisation of HRP cells to PARPi via HRR inhibition. PMC11369084
SMS-SAN cells 1 µM 3 days Increased the expression of two pro-apoptotic proteins, BAX and PUMA, providing a mechanism for the effect of the CHK1 inhibitor PMC6696225
CHP134 cells 1 µM 3 days Increased the expression of two pro-apoptotic proteins, BAX and PUMA, providing a mechanism for the effect of the CHK1 inhibitor PMC6696225
NB-39-nu cells 1 µM 3 days Induced DNA double-strand breaks and activated the ATM-p53-p21 axis of the DDR pathway, which rendered the cells relatively insensitive to the antiproliferative effects of the CHK1 inhibitor PMC6696225
SK-N-BE cells 1 µM 3 days Induced DNA double-strand breaks and activated the ATM-p53-p21 axis of the DDR pathway, which rendered the cells relatively insensitive to the antiproliferative effects of the CHK1 inhibitor PMC6696225

In Vivo:

Species
Animal Model
Administration Dosage Frequency Description References
Mice SKOV3 CR xenograft tumors Oral and Intraperitoneal injection 60 mg/kg 2 weeks To assess the antitumor effects of PF-477736 in combination with cisplatin. PMC7474466

Protocol

Bio Calculators
Preparing Stock Solutions 1mg 5mg 10mg

1 mM

5 mM

10 mM

2.38mL

0.48mL

0.24mL

11.92mL

2.38mL

1.19mL

23.84mL

4.77mL

2.38mL

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