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Chemical Structure| 1462249-75-7 Chemical Structure| 1462249-75-7

Structure of PFK158
CAS No.: 1462249-75-7

Chemical Structure| 1462249-75-7

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PFK-158 is a potent and selective inhibitor of PFKFB3 that is currently being investigated in a phase I study in patients with advanced solid malignancies.

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Product Details of PFK158

CAS No. :1462249-75-7
Formula : C18H11F3N2O
M.W : 328.29
SMILES Code : O=C(C1=CC=NC=C1)/C=C/C2=NC3=CC(C(F)(F)F)=CC=C3C=C2
MDL No. :MFCD28386154
InChI Key :IAJOMYABKVAZCN-AATRIKPKSA-N
Pubchem ID :71730058

Safety of PFK158

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302
Precautionary Statements:P280-P305+P351+P338

Isoform Comparison

Biological Activity

In Vitro:

Cell Line
Concentration Treated Time Description References
Acute myeloid leukemia cells 0.9 μM 96 hours Evaluate the inhibitory effect of PFK158 combined with meclizine on AML cells, showing synergistic inhibition PMC7085447
DMS53 cells 0, 2.5, 5, 10 μM 24 hours Inhibition of glycolysis, proliferation, spheroid formation, and the expression of cancer stem cell markers CD133, Aldh1, CD44, Sox2, and ABCG2 PMC9374593
H1876 cells 0, 2.5, 5, 10 μM 24 hours Inhibition of glycolysis, proliferation, spheroid formation, and the expression of cancer stem cell markers CD133, Aldh1, CD44, Sox2, and ABCG2 PMC9374593
H1882 cells 0, 2.5, 5, 10 μM 24 hours Inhibition of glycolysis, proliferation, spheroid formation, and the expression of cancer stem cell markers CD133, Aldh1, CD44, Sox2, and ABCG2 PMC9374593
H1048 cells 0, 2.5, 5, 10 μM 24 hours Inhibition of glycolysis, proliferation, spheroid formation, and the expression of cancer stem cell markers CD133, Aldh1, CD44, Sox2, and ABCG2 PMC9374593
Patient-derived ascites cells 3-5µM 24 hours To evaluate the effect of PFK158 on cell viability, results showed that PFK158 treatment reduced cell viability and restored primary cilia formation PMC8173968
OVCAR5 10µM 24 hours To evaluate the effect of PFK158 on primary cilia formation, results showed that PFK158 treatment significantly restored primary cilia formation PMC8173968
OVCAR8 10µM 24 hours To evaluate the effect of PFK158 on primary cilia formation, results showed that PFK158 treatment significantly restored primary cilia formation PMC8173968
EMMeso 0-30μM 24 and 48 hours PFK158 treatment inhibited MPM cell viability with IC50 values ranging from 3 to 12μM PMC6764980
NCI-H28 0-30μM 24 and 48 hours PFK158 treatment inhibited MPM cell viability with IC50 values ranging from 3 to 12μM PMC6764980
OVCAR8 cells 5 µM 48 hours To evaluate the effect of PFK158 on PARPi resistance, results showed that PFK158 inhibited PFKFB3 activity and enhanced PARPi sensitivity. PMC11762855
SKOV3 cells 5 µM 48 hours To evaluate the effect of PFK158 on PARPi resistance, results showed that PFK158 inhibited PFKFB3 activity and enhanced PARPi sensitivity. PMC11762855
ARK-2 0-20 μM 24-72 hours Inhibited cell proliferation, reduced glucose uptake, ATP production, and lactate dehydrogenase activity PMC7906909
HEC-1B 0-20 μM 24-72 hours Inhibited cell proliferation, reduced glucose uptake, ATP production, and lactate dehydrogenase activity PMC7906909
HeyA8MDR 5μM 30 minutes To evaluate the effect of PFK158 on glucose uptake, results showed that PFK158 treatment significantly decreased glucose uptake PMC6261695
HeyA8 5μM 30 minutes To evaluate the effect of PFK158 on glucose uptake, results showed that PFK158 treatment significantly decreased glucose uptake PMC6261695
C13 5μM 30 minutes To evaluate the effect of PFK158 on glucose uptake, results showed that PFK158 treatment significantly decreased glucose uptake PMC6261695
EMMeso 5 µM 24 hours PFK158 treatment inhibited MPM cell viability with IC50 values ranging from 3 to 12μM PMC9519537
NCI-H2052 2.5 µM 24 hours PFK158 significantly decreased SOX2 and CD133 transcript levels in H2052 cells. PMC9519537
NCI-H28 2.5 µM 24 hours PFK158 treatment inhibited MPM cell viability with IC50 values ranging from 3 to 12μM PMC9519537
OV2008 5μM 30 minutes To evaluate the effect of PFK158 on glucose uptake, results showed that PFK158 treatment significantly decreased glucose uptake PMC6261695
THP-1 monocytes 2.5, 5, or 10 μM 30 minutes To evaluate the effect of the PFKFB3 inhibitor 3PO on the chemotaxis of THP-1 monocytes, results showed that 3PO inhibited MCP-1-induced chemotaxis of THP-1 cells. PMC10420406
DMS79 2.5 μM 72 hours To evaluate the effect of PFK158 on ATP production, glucose uptake, and lactate secretion in MYC-low SCLC cell lines. Results showed that PFK158 had minimal effect on ATP production, glucose uptake, and lactate. PMC8461854
H446 2.5 μM 72 hours To evaluate the effect of PFK158 on ATP production, glucose uptake, and lactate secretion in MYC-high SCLC cell lines. Results showed that PFK158 significantly attenuated glucose uptake, ATP production, and lactate. PMC8461854
HuH7 cells 2 or 5 μM 24 and 48 hrs PMC7085447
HepG2 cells 2 or 5 μM 24 and 48 hrs Evaluate the effect of SR9009 on BMAL1 mRNA expression PMC7085447

In Vivo:

Species
Animal Model
Administration Dosage Frequency Description References
NOG mice Human hepatocarcinoma cell line xenotransplantation model Oral 25 mg/kg Once daily for two weeks Evaluate the inhibitory effect of PFK158 combined with meclizine on liver cancer growth, showing significant reduction in tumor burden PMC7085447
SCID-NSG mice H1048 CSC xenograft model Intraperitoneally (ip) 25 mg/kg Twice a week for 3 weeks PFK158 treatment and PFKFB3 knockdown significantly reduced tumor growth and weight with reduced expression of cancer stem cell markers, ABCG2, and YAP/TAZ PMC9374593
Nude mice OVCAR5 xenograft model Intraperitoneal injection 50 mg/kg Once a week for 4 weeks To evaluate the effect of PFK158 in combination with carboplatin, results showed that PFK158 combined with carboplatin significantly inhibited tumor growth and metastasis PMC8173968
Female athymic nude mice EMMeso xenograft model Subcutaneous injection 30 mg/kg Twice a week for 2 weeks PFK158 alone or in combination with carboplatin significantly inhibited tumor growth PMC6764980
BALB/c nude mice SKOV3 xenograft models Intraperitoneally 35 mg/kg Twice weekly for 28 days To evaluate the in vivo efficacy of PFK158 combined with PARPi, results showed that the combination significantly inhibited tumor growth and increased DNA damage. PMC11762855
Nude mice HEC-1B and ARK-2 xenograft models Intraperitoneal injection 35 mg/kg Twice weekly for 14 days Significantly inhibited tumor growth, reduced tumor volume and weight, and enhanced chemosensitivity PMC7906909
Female athymic nude mice Highly metastatic PTX-resistant ovarian mouse model Intraperitoneal injection 25 mg/kg PFK158 every 3rd day, CBPt every 3rd day, PTX every 5th day, for 28 days To evaluate the effect of PFK158 alone or in combination with CBPt/PTX on tumor growth and ascites, results showed that the combination treatment significantly reduced tumor weight and ascites PMC6261695
Female athymic nude mice MPM xenograft model 30 mg/kg Twice a week for 2 weeks PFK158 significantly reduced tumour burden, tumour weight and tumour volume in TIC-mediated MPM xenografts. PMC9519537
Mice Apoe−/− mice Intraperitoneal injection 2 mg/kg 3 times per week for 5 weeks To evaluate the effect of PFK158 on plaque stability, results showed that PFK158 improved plaque stability. PMC10420406
Nude mice H446 xenograft model Intraperitoneal injection 25 mg/kg Every 2 days for a total of six treatments To evaluate the effect of PFK158 on tumor growth in MYC-high SCLC xenograft models. Results showed that PFK158 significantly delayed tumor growth. PMC8461854

Protocol

Bio Calculators
Preparing Stock Solutions 1mg 5mg 10mg

1 mM

5 mM

10 mM

3.05mL

0.61mL

0.30mL

15.23mL

3.05mL

1.52mL

30.46mL

6.09mL

3.05mL

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