Daporinad

Last updated

Daporinad
Daporinad structure.png
Clinical data
Drug class NAMPT inhibitor
Identifiers
  • (E)-N-[4-(1-benzoylpiperidin-4-yl)butyl]-3-pyridin-3-ylprop-2-enamide
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard 100.316.982 OOjs UI icon edit-ltr-progressive.svg
Chemical and physical data
Formula C24H29N3O2
Molar mass 391.515 g·mol−1
3D model (JSmol)
  • C1CN(CCC1CCCCNC(=O)/C=C/C2=CN=CC=C2)C(=O)C3=CC=CC=C3
  • InChI=1S/C24H29N3O2/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)/b12-11+
  • Key:KPBNHDGDUADAGP-VAWYXSNFSA-N

Daporinad (FK866, APO866), is a drug which acts as a selective inhibitor of the enzyme nicotinamide phosphoribosyltransferase (NAMPT). Levels of this enzyme are elevated in certain forms of cancer such as leukemia, and it was hoped that NAMPT inhibitors would be useful in the treatment of cancer. Unfortunately, dapinorad was unsuccessful in clinical trials due to lack of efficacy, but it still has antiinflammatory effects and may be useful for other medical applications such as arthritis, as well as being widely used as a tool compound for the study of NAMPT and its function. [1] [2] [3] [4] [5] [6] [7]

Daporinad was originally identified and developed by Klinge Pharma G.m.b.H., [8] Development rights then moved through a corporate chain in which Fujisawa Deutschland GmbH [9] which later merged into Astellas held APO866/FK866 and subsequently out-licensed the worldwide development and marketing rights to the Danish oncology company TopoTarget in 2005, after which TopoTarget merged with BioAlliance Pharma to form Onxeo, which later rebranded as Valerio Therapeutics. [10]

References

  1. ↑ Bi TQ, Che XM (July 2010). "Nampt/PBEF/visfatin and cancer". Cancer Biology & Therapy. 10 (2): 119–125. doi:10.4161/cbt.10.2.12581. PMID   20647743.
  2. ↑ Montecucco F, Cea M, Cagnetta A, Damonte P, Nahimana A, Ballestrero A, et al. (2013). "Nicotinamide phosphoribosyltransferase as a target in inflammation- related disorders". Current Topics in Medicinal Chemistry. 13 (23): 2930–2938. doi:10.2174/15680266113136660208. PMID   24171767.
  3. ↑ Galli U, Travelli C, Massarotti A, Fakhfouri G, Rahimian R, Tron GC, et al. (August 2013). "Medicinal chemistry of nicotinamide phosphoribosyltransferase (NAMPT) inhibitors". Journal of Medicinal Chemistry. 56 (16): 6279–6296. doi:10.1021/jm4001049. PMID   23679915.
  4. ↑ Franco-Trepat E, Alonso-Pérez A, Guillán-Fresco M, Jorge-Mora A, Gualillo O, Gómez-Reino JJ, et al. (July 2019). "Visfatin as a therapeutic target for rheumatoid arthritis". Expert Opinion on Therapeutic Targets. 23 (7): 607–618. doi:10.1080/14728222.2019.1617274. PMID   31074669.
  5. ↑ Ghanem MS, Monacelli F, Nencioni A (May 2021). "Advances in NAD-Lowering Agents for Cancer Treatment". Nutrients. 13 (5): 1665. doi: 10.3390/nu13051665 . PMC   8156468 . PMID   34068917.
  6. ↑ Wei Y, Xiang H, Zhang W (2022). "Review of various NAMPT inhibitors for the treatment of cancer". Frontiers in Pharmacology. 13 970553. doi: 10.3389/fphar.2022.970553 . PMC   9490061 . PMID   36160449.
  7. ↑ Mylonakis A, Kozadinos A, Frountzas M, Kapetanakis EI, Lidoriki I, Despotidis M, et al. (April 2025). "The Role of Visfatin in Gastric and Esophageal Cancer: From Biomarker to Therapeutic Target". Cancers. 17 (8): 1377. doi: 10.3390/cancers17081377 . PMC   12025392 . PMID   40282553.
  8. ↑ WO 1997/048696A1,Biedermann E, Hasmann M, Löser R, Rattel B, Reiter F, Schein B, Seibel K, Vogt K,"Pyridyl alkene- and pyridyl alkyne-acid amides as cytostatics and immunosuppressives",published 1997-12-24, assigned to Klinge Pharma GmbH Example 7: N-[4-(l-benzoylpiperidin-4-yl)-butyl]-3-(pyridin-3-yl)-acrylamide (substance 159)
  9. ↑ Hasmann M, Schemainda I (November 2003). "FK866, a highly specific noncompetitive inhibitor of nicotinamide phosphoribosyltransferase, represents a novel mechanism for induction of tumor cell apoptosis". Cancer Research. 63 (21): 7436–7442. PMID   14612543.
  10. ↑ "Valerio Therapeutics SA". Synapse. PatSnap.
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