| Identification | Back Directory | [Name]
3PO | [CAS]
18550-98-6 | [Synonyms]
3 PO;3-PO
3PO >=98% (HPLC)
3PO (inhibitor of glucose metabolism)
(E)-3-Pyridin-3-yl-1-pyridin-4-yl-propenone
2-Propen-1-one, 3-(3-pyridinyl)-1-(4-pyridinyl)-, (2E)- | [Molecular Formula]
C13H10N2O | [MDL Number]
MFCD00224002 | [MOL File]
18550-98-6.mol | [Molecular Weight]
210.23 |
| Chemical Properties | Back Directory | [Boiling point ]
387.8±42.0 °C(Predicted) | [density ]
1.192±0.06 g/cm3(Predicted) | [storage temp. ]
2-8°C | [solubility ]
Soluble in DMSO (up to 15 mg/ml) or in Ethanol (up to 5 mg/ml) | [form ]
powder | [pka]
3.49±0.11(Predicted) | [color ]
white to beige | [Stability:]
Stable for 1 year from date of purchase as supplied. Solutions in DMSO or ethanol may be stored at -20°C for up to 3 months. | [InChI]
InChI=1S/C13H10N2O/c16-13(12-5-8-14-9-6-12)4-3-11-2-1-7-15-10-11/h1-10H/b4-3+ | [InChIKey]
UOWGYMNWMDNSTL-ONEGZZNKSA-N | [SMILES]
C(C1C=CN=CC=1)(=O)/C=C/C1=CC=CN=C1 |
| Hazard Information | Back Directory | [Description]
3PO (18550-98-6) is an inhibitor of the metabolic enzyme 6-Phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3).? PFKFB3 is constitutively expressed by neoplastic cells and is required for the high glycolytic rate (Warburg Effect) of these cells. 3PO inhibits PFKFB3 (IC50?= 1.4 – 24 μM for various cancer cell lines), suppresses glucose uptake, and lowers intracellular concentrations of Fru-2,6-BP, lactate, ATP, NAD+, and NADH.1? Inhibition of cancer cell metabolism via blocking the action of PFKFB3 has been studied in various models.2-4? Inhibition of PFKFB3 has been shown to induce autophagy as a survival mechanism in cancer cells.5? 3PO has also been used to reduce pathological angiogenesis.6 | [Uses]
3PO is an inhibitor of PFKFB3. 3PO attenuates the proliferation of several cancer cell lines with IC50s of 1.4-24 μmol/L. 3PO suppresses glucose uptake and decreases the intracellular concentration of Fru-2,6-BP, lactate, ATP, NAD+ and NADH. 3PO can be used for the research of cancer[1]. | [Definition]
ChEBI: 3PO is a member of the class of pyridines that is pyridine substituted by a 3-oxo-3-(pyridin-4-yl)prop-1-en-1-yl group at position 3. An inhibitor of PFKFB3 kinase, an enzyme with a key role in glycolysis. It has a role as an antineoplastic agent, an angiogenesis inhibitor, an autophagy inducer, an apoptosis inducer and an EC 2.7.1.105 (6-phosphofructo-2-kinase) inhibitor. It is a member of pyridines and an enone. | [Biochem/physiol Actions]
3PO is a potent and selective inhibitor of PFKFB3 (6-Phosphofructo-2-kinase/fructose-2,6-bisphosphatase) that reduces glycolytic flux and suppresses glucose uptake. 3PO is selectively cytostatic to transformed cells and suppresses the growth of established tumor in mice. | [in vivo]
3PO (0.07 mg/g; i.p. once per day for 14 days) inhibits the growth of Lewis lung carcinoma xenografts in C57Bl/6 mice[1].
3PO (0.07 mg/g; i.p. three sequential daily injections followed by 3 off days for 14 days) inhibits the tumor growth in BALB/c athymic mice[1].
3PO (0.07 mg/g; i.p. two daily injections followed a 7-day rest for 14 days) inhibits the tumor growth in BALB/c athymic mice[1].
3PO (0.07 mg/g; i.p. once) inhibits Fru-2,6-BP and glucose uptake in C57Bl/6 mice[1]. | Animal Model: | Female C57Bl/6 mice with Lewis lung carcinoma xenografts[1] | | Dosage: | 0.07 mg/g | | Administration: | Intraperitoneal injection; 0.07 mg/g once a day; for 14 days | | Result: | Suppressed the growth of Lewis lung carcinoma xenografts in C57Bl/6 mice compared to the control group. |
| Animal Model: | Female BALB/c athymic mice with MDA-MB231 human breast adenocarcinoma xenografts[1] | | Dosage: | 0.07 mg/g | | Administration: | Intraperitoneal injection; 0.07 mg/g three sequential daily injections of either DMSO or 3PO followed by 3 off days; for 14 days | | Result: | Suppressed xenograft tumorigenic growth of MDA-MB231 cells compared with the controls. |
| Animal Model: | Female BALB/c athymic mice with HL-60 leukemia xenografts[1] | | Dosage: | 0.07 mg/g | | Administration: | Intraperitoneal injection; 0.07 mg/g two daily injections followed a 7-day rest; for 14 days | | Result: | Suppressed xenograft tumorigenic growth of HL-60 leukemia compared with the controls, especially from the second administration cycle. |
| Animal Model: | Female C57Bl/6 mice with Lewis lung carcinoma xenografts[1] | | Dosage: | 0.07 mg/g | | Administration: | Intraperitoneal injection; once | | Result: | Decreased Fru-2,6-BP and glucose uptake in C57Bl/6 mice compared to control group. |
| [storage]
Store at -20°C | [References]
1) Clem?et al.?(2008),?Small-molecule inhibition of 6-phosphofructo-2-kinase activity suppresses glycolytic flux and tumor growth; Mol. Cancer Ther.?7?110
2) Clem?et al.?(2013),?Targeting 6-phosphofructo-2-kinase (PFKFB3) as a therapeutic strategy against cancer; Mol. Cancer Ther.?12?1461
3) Lea?et al.?(2015),?Inhibition of Growth of Bladder Cancer Cells by 3-(3-Pyridinyl)-1-(4-pyridinyl)-2-propen-1-one in Combination with Other Compounds Affecting Glucose Metabolism; Anticancer Res.?35?5889
4) Lea?et al.?(2016),?Inhibition of Growth by Combined Treatment with Inhibitors of Lactate Dehydrogenase and either Phenformin or Inhibitors of 6-Phosphofructo-2-kinase/Fructose-2,6-bisphosphatae 3; Anticancer Res.?36?1479
5) Klarer?et al.?(2014),?Inhibition of 6-phosphofructo-2-kinase (PFKFB3) induces autophagy as a survival mechanism; Cancer Metab.?2?2
6) Schoors?et al.?(2014),?Partial and transient reduction of glycolysis by PFKFB3 blockade reduces pathological angiogenesis; Cell Metab.?19?37 |
|
| Company Name: |
Sigma-Aldrich
|
| Telephone: |
021-61415566 800-8193336 |
| Website: |
https://www.sigmaaldrich.cn |
|