Synonym
PFK015; PFK 015; PFK015.
IUPAC/Chemical Name
(E)-3-(pyridin-3-yl)-1-(quinolin-3-yl)prop-2-en-1-one
InChi Key
LFVHDRPWNYRNLS-BQYQJAHWSA-N
InChi Code
InChI=1S/C17H12N2O/c20-17(8-7-13-4-3-9-18-11-13)15-10-14-5-1-2-6-16(14)19-12-15/h1-12H/b8-7+
SMILES Code
O=C(C1=CC2=CC=CC=C2N=C1)/C=C/C3=CC=CN=C3
Purity
>98% (or refer to the Certificate of Analysis)
Shipping Condition
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility
Soluble in DMSO, not in water
Shelf Life
>2 years if stored properly
Drug Formulation
This drug may be formulated in DMSO
Stock Solution Storage
0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code
2934.99.9001
Biological target:
PFK-015, a derivative of 3PO, is a specific PFKFB3 inhibitor.
In vitro activity:
PFK-15, a PFKFB3 inhibitor, obviously induced apoptosis, cell viability loss, and inhibited cell proliferation/migration. Besides, PFK-15 was also found to induce necroptosis, as it not only up-regulated the phosphorylated RIP1, RIP3 and MLKL, but also enhanced the interaction between RIP3 and RIP1/MLKL, all of which are characterization of necroptosis induction. Besides, PFK-15 increased the γ-H2AX level and micronuclei formation, markers for genome instability, and inhibition of necroptosis attenuated these phenotypes. Collectively, the presented data demonstrated that PFK-15 induced genome instability and necroptosis, and deprivation of necroptosis attenuated cytotoxicity and genotoxicity of PFK-15 in colorectal cancer cells, thereby revealing a more intimate relationship among PFKFB3, necroptosis and genome instability.
Reference: Am J Cancer Res. 2021 May 15;11(5):2062-2080. https://pubmed.ncbi.nlm.nih.gov/34094669/
In vivo activity:
Treatment using PFK-015 in immunodeficient (nude) mice in in vivo study after sub-dermal flank inoculation with esophageal cancer cells confirmed with our in vitro experiments: showing a marked reduction in tumor volume and final tumor mass when compared with the vehicle group (Figure 1(a-c), S1D). Together, these results confirm that PFK-015 can indeed inhibit tumor growth both in vitro and in immunodeficient in vivo models.
Reference: Oncoimmunology. 2022 May 25;11(1):2079182. https://pubmed.ncbi.nlm.nih.gov/35707221/
|
Solvent |
mg/mL |
mM |
comments |
| Solubility |
| DMF |
20.0 |
76.84 |
|
| DMF:PBS (pH 7.2) (1:3) |
0.3 |
0.96 |
|
| DMSO |
20.4 |
78.41 |
|
| Ethanol |
1.0 |
3.84 |
|
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.
Preparing Stock Solutions
The following data is based on the
product
molecular weight
260.30
Batch specific molecular weights may vary
from batch to batch
due to the degree of hydration, which will
affect the solvent
volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass |
1 mg |
5 mg |
10 mg |
| 1 mM |
1.15 mL |
5.76 mL |
11.51 mL |
| 5 mM |
0.23 mL |
1.15 mL |
2.3 mL |
| 10 mM |
0.12 mL |
0.58 mL |
1.15 mL |
| 50 mM |
0.02 mL |
0.12 mL |
0.23 mL |
Formulation protocol:
1. Yan S, Li Q, Zhang D, Wang X, Xu Y, Zhang C, Guo D, Bao Y. Necroptosis pathway blockage attenuates PFKFB3 inhibitor-induced cell viability loss and genome instability in colorectal cancer cells. Am J Cancer Res. 2021 May 15;11(5):2062-2080. PMID: 34094669; PMCID: PMC8167677.
2. Clem BF, O'Neal J, Tapolsky G, Clem AL, Imbert-Fernandez Y, Kerr DA 2nd, Klarer AC, Redman R, Miller DM, Trent JO, Telang S, Chesney J. Targeting 6-phosphofructo-2-kinase (PFKFB3) as a therapeutic strategy against cancer. Mol Cancer Ther. 2013 Aug;12(8):1461-70. doi: 10.1158/1535-7163.MCT-13-0097. Epub 2013 May 14. PMID: 23674815; PMCID: PMC3742633.
3. Zheng JB, Wong CW, Liu J, Luo XJ, Zhou WY, Chen YX, Luo HY, Zeng ZL, Ren C, Xie XM, Wang DS. Glucose metabolism inhibitor PFK-015 combined with immune checkpoint inhibitor is an effective treatment regimen in cancer. Oncoimmunology. 2022 May 25;11(1):2079182. doi: 10.1080/2162402X.2022.2079182. PMID: 35707221; PMCID: PMC9191911.
In vitro protocol:
1. Yan S, Li Q, Zhang D, Wang X, Xu Y, Zhang C, Guo D, Bao Y. Necroptosis pathway blockage attenuates PFKFB3 inhibitor-induced cell viability loss and genome instability in colorectal cancer cells. Am J Cancer Res. 2021 May 15;11(5):2062-2080. PMID: 34094669; PMCID: PMC8167677.
2. Clem BF, O'Neal J, Tapolsky G, Clem AL, Imbert-Fernandez Y, Kerr DA 2nd, Klarer AC, Redman R, Miller DM, Trent JO, Telang S, Chesney J. Targeting 6-phosphofructo-2-kinase (PFKFB3) as a therapeutic strategy against cancer. Mol Cancer Ther. 2013 Aug;12(8):1461-70. doi: 10.1158/1535-7163.MCT-13-0097. Epub 2013 May 14. PMID: 23674815; PMCID: PMC3742633.
In vivo protocol:
1. Zheng JB, Wong CW, Liu J, Luo XJ, Zhou WY, Chen YX, Luo HY, Zeng ZL, Ren C, Xie XM, Wang DS. Glucose metabolism inhibitor PFK-015 combined with immune checkpoint inhibitor is an effective treatment regimen in cancer. Oncoimmunology. 2022 May 25;11(1):2079182. doi: 10.1080/2162402X.2022.2079182. PMID: 35707221; PMCID: PMC9191911.
2. Clem BF, O'Neal J, Tapolsky G, Clem AL, Imbert-Fernandez Y, Kerr DA 2nd, Klarer AC, Redman R, Miller DM, Trent JO, Telang S, Chesney J. Targeting 6-phosphofructo-2-kinase (PFKFB3) as a therapeutic strategy against cancer. Mol Cancer Ther. 2013 Aug;12(8):1461-70. doi: 10.1158/1535-7163.MCT-13-0097. Epub 2013 May 14. PMID: 23674815; PMCID: PMC3742633.
1: Lu Z, Pan Y, Wang S, Wu J, Miao C, Wang Z. Multi-omics and immunogenomics analysis revealed PFKFB3 as a targetable hallmark and mediates sunitinib resistance in papillary renal cell carcinoma: in silico study with laboratory verification. Eur J Med Res. 2024 Apr 15;29(1):236. doi: 10.1186/s40001-024-01808-5. PMID: 38622715; PMCID: PMC11017615.
2: Ling X, Liu L, Jiang A, Shi X, Liu L, Wang X, Lu C, Ren C, Yu Z. PFKFB3 promotes endometriosis cell proliferation via enhancing the protein stability of β-catenin. Mol Cell Endocrinol. 2024 Jan 1;579:112083. doi: 10.1016/j.mce.2023.112083. Epub 2023 Oct 9. PMID: 37820851.
3: Zheng JB, Wong CW, Liu J, Luo XJ, Zhou WY, Chen YX, Luo HY, Zeng ZL, Ren C, Xie XM, Wang DS. Glucose metabolism inhibitor PFK-015 combined with immune checkpoint inhibitor is an effective treatment regimen in cancer. Oncoimmunology. 2022 May 25;11(1):2079182. doi: 10.1080/2162402X.2022.2079182. PMID: 35707221; PMCID: PMC9191911.
4: Zhang Y, Wang X, Li X, Dong L, Hu X, Nie T, Lu Y, Lu X, Pang J, Li G, Yang X, Li C, You X. Synergistic Effect of Colistin Combined with PFK-158 against Colistin-Resistant Enterobacteriaceae. Antimicrob Agents Chemother. 2019 Jun 24;63(7):e00271-19. doi: 10.1128/AAC.00271-19. PMID: 30988150; PMCID: PMC6591609.
