Synonym
FK-866 Hydrochloride; FK 866 Hydrochloride; FK866 Hydrochloride; FK-866 HCl; FK 866 HCl; FK866 HCl; APO-866 hydrochloride; APO-866 HCl; K22.175 HCl;
IUPAC/Chemical Name
N-[4-(1-Benzoyl-4-piperidinyl)butyl]-3-(3-pyridinyl)-2-propenamide hydrochloride
InChi Key
MULSIBUGDPOSHV-CALJPSDSSA-N
InChi Code
InChI=1S/C24H29N3O2.ClH/c28-23(12-11-21-8-6-15-25-19-21)26-16-5-4-7-20-13-17-27(18-14-20)24(29)22-9-2-1-3-10-22;/h1-3,6,8-12,15,19-20H,4-5,7,13-14,16-18H2,(H,26,28);1H/b12-11+;
SMILES Code
O=C(NCCCCC1CCN(C(C2=CC=CC=C2)=O)CC1)/C=C/C3=CC=CN=C3.[H]Cl
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
Shelf Life
>3 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:
(E)-Daporinad (FK866) is an effective inhibitor of nicotinamide phosphoribosyltransferase (NMPRTase; Nampt) with an IC50 of 0.09 nM.
In vitro activity:
In the present study, FK866 was identified to inhibit the capability of invasion and metastasis of cells from the HCC MHCC97-H line in a dose-dependent manner using a wound healing assay, an invasion assay and a migration assay. Furthermore, FK866 markedly decreased NAD+ and adenosine 5'-triphosphate content in MHCC97-H cells by inhibiting NAMPT expression. The results of the present study also revealed that FK866 led to a decrease in the expression of SIRT1, and to increased and decreased levels of the EMT marker proteins epithelial cadherin and vimentin, respectively, in MHCC97-H cells. Furthermore, FK866 inhibited the SIRT1mediated EMT, invasion and migration of HCC cells by decreasing the expression of the NAMPT/NAD+ pathway. Taken together, the results of the present study suggest that FK866 may be an effective drug targeting HCC metastasis and invasion, and that the NAMPT/NAD+/SIRT1 pathway may be a potential therapeutic target for HCC.
Reference: Oncol Lett. 2018 Dec; 16(6): 7231–7238. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6256367/
In vivo activity:
In vivo, mice were pretreated with FK866 at 24, 12, and 0.5 h before treatment with GaIN/LPS and ConA. 3-methyladenine (3MA) or rapamycin were used to determine the role of autophagy in FK866-conferred hepatoprotection. As shown in Fig. 1f, the ATG7 and LC3B-II levels in the livers with FK866 pretreatment were higher than those without FK866 after GaIN/LPS treatment, whereas the p62 levels were lower in the FK866 + GaIN/LPS group than those in the vehicle + GaIN/LPS group. As shown in Fig. 1g, FK866 pretreatment demonstrated an increase in LC3B-II expression levels, and the administration of CQ led to further significant accumulation of LC3B-II in mice liver tissue, demonstrating that LC3B-II accumulation was not due to impaired autophagic maturation step. Taken together, these findings confirmed that FK866 could enhance hepatic autophagic activity in ALF mice models.
Reference: Sci Rep. 2017; 7: 2206. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5438370/
|
Solvent |
mg/mL |
mM |
| Solubility |
| DMSO |
0.0 |
0.00 |
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
427.97
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. Guo E, Li R, Yang J, Zhang J, Li A, Yang Y, Liu S, Liu A, Jiang X. FK866 attenuates acute hepatic failure through c-jun-Nterminal kinase (JNK)-dependent autophagy. Sci Rep. 2017 May 19;7(1):2206. doi: 10.1038/s41598-017-02318-7. PMID: 28526886; PMCID: PMC5438370. 2. Zhang B, Shi D, Zhang X, Liang G, Liu W, Qiao S. FK866 inhibits the epithelial-mesenchymal transition of hepatocarcinoma MHCC97-H cells. Oncol Lett. 2018 Dec;16(6):7231-7238. doi: 10.3892/ol.2018.9541. Epub 2018 Oct 3. PMID: 30546461; PMCID: PMC6256367.
3. Lee J, Kim H, Lee JE, Shin SJ, Oh S, Kwon G, Kim H, Choi YY, White MA, Paik S, Cheong JH, Kim HS. Selective Cytotoxicity of the NAMPT Inhibitor FK866 Toward Gastric Cancer Cells With Markers of the Epithelial-Mesenchymal Transition, Due to Loss of NAPRT. Gastroenterology. 2018 Sep;155(3):799-814.e13. doi: 10.1053/j.gastro.2018.05.024. Epub 2018 Jul 30. PMID: 29775598.
In vitro protocol:
1. Guo E, Li R, Yang J, Zhang J, Li A, Yang Y, Liu S, Liu A, Jiang X. FK866 attenuates acute hepatic failure through c-jun-Nterminal kinase (JNK)-dependent autophagy. Sci Rep. 2017 May 19;7(1):2206. doi: 10.1038/s41598-017-02318-7. PMID: 28526886; PMCID: PMC5438370. 2. Zhang B, Shi D, Zhang X, Liang G, Liu W, Qiao S. FK866 inhibits the epithelial-mesenchymal transition of hepatocarcinoma MHCC97-H cells. Oncol Lett. 2018 Dec;16(6):7231-7238. doi: 10.3892/ol.2018.9541. Epub 2018 Oct 3. PMID: 30546461; PMCID: PMC6256367.
In vivo protocol:
1. Guo E, Li R, Yang J, Zhang J, Li A, Yang Y, Liu S, Liu A, Jiang X. FK866 attenuates acute hepatic failure through c-jun-Nterminal kinase (JNK)-dependent autophagy. Sci Rep. 2017 May 19;7(1):2206. doi: 10.1038/s41598-017-02318-7. PMID: 28526886; PMCID: PMC5438370. 2. Lee J, Kim H, Lee JE, Shin SJ, Oh S, Kwon G, Kim H, Choi YY, White MA, Paik S, Cheong JH, Kim HS. Selective Cytotoxicity of the NAMPT Inhibitor FK866 Toward Gastric Cancer Cells With Markers of the Epithelial-Mesenchymal Transition, Due to Loss of NAPRT. Gastroenterology. 2018 Sep;155(3):799-814.e13. doi: 10.1053/j.gastro.2018.05.024. Epub 2018 Jul 30. PMID: 29775598.
1: Qu SD, Liu GX. Daporinad in vitro metabolite profiling via rat, dog, monkey and human liver microsomes by liquid chromatography/quadrupole-orbitrap mass spectrometry. Rapid Commun Mass Spectrom. 2021 Sep 30;35(18):e9150. doi: 10.1002/rcm.9150. PMID: 34159659.
2: Park M, Lee BI, Choi J, Park Y, Park SJ, Lim JH, Lee J, Shin YG. Quantitative Analysis of Daporinad (FK866) and Its In Vitro and In Vivo Metabolite Identification Using Liquid Chromatography-Quadrupole-Time-of-Flight Mass Spectrometry. Molecules. 2022 Mar 21;27(6):2011. doi: 10.3390/molecules27062011. PMID: 35335372; PMCID: PMC8954816.
3: Shen Y, Wei Z, Zhou C, Song J, Wang J, Wang J, Wu L, Fang S, Shen Z. Arylsulfatase I is a prognostic biomarker for head and neck squamous cell carcinoma and Pan-cancer. J Clin Lab Anal. 2022 Sep;36(9):e24600. doi: 10.1002/jcla.24600. Epub 2022 Jul 23. PMID: 35870182; PMCID: PMC9459304.
4: Peng Q, Jia SH, Parodo J, Ai Y, Marshall JC. Pre-B cell colony enhancing factor induces Nampt-dependent translocation of the insulin receptor out of lipid microdomains in A549 lung epithelial cells. Am J Physiol Endocrinol Metab. 2015 Feb 15;308(4):E324-33. doi: 10.1152/ajpendo.00006.2014. Epub 2014 Dec 16. PMID: 25516545.
5: Sauriol A, Carmona E, Udaskin ML, Radulovich N, Leclerc-Desaulniers K, Rottapel R, Oza AM, Lheureux S, Provencher DM, Mes-Masson AM. Inhibition of nicotinamide dinucleotide salvage pathway counters acquired and intrinsic poly(ADP-ribose) polymerase inhibitor resistance in high-grade serous ovarian cancer. Sci Rep. 2023 Feb 27;13(1):3334. doi: 10.1038/s41598-023-30081-5. PMID: 36849518; PMCID: PMC9970983.
