Denifanstat

Denifanstat
Clinical data
Other names	TVB-2640
Legal status
Legal status	Investigational;
Identifiers
	IUPAC name 4-[1-[4-Cyclobutyl-2-methyl-5-(5-methyl-1H-1,2,4-triazol-3-yl)benzoyl]piperidin-4-yl]benzonitrile;
CAS Number	1399177-37-7;
PubChem CID	66548316;
ChemSpider	58955989;
UNII	4GF95B2LZA;
ChEMBL	ChEMBL3661754;
Chemical and physical data
Formula	C27H29N5O
Molar mass	439.563 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES CC1=CC(=C(C=C1C(=O)N2CCC(CC2)C3=CC=C(C=C3)C#N)C4=NNC(=N4)C)C5CCC5;
	InChI InChI=1S/C27H29N5O/c1-17-14-24(22-4-3-5-22)25(26-29-18(2)30-31-26)15-23(17)27(33)32-12-10-21(11-13-32)20-8-6-19(16-28)7-9-20/h6-9,14-15,21-22H,3-5,10-13H2,1-2H3,(H,29,30,31); Key:BBGOSBDSLYHMRA-UHFFFAOYSA-N;

Denifanstat (TVB-2640) is a small-molecule drug and fatty acid synthase inhibitor. Developed by Sagimet Biosciences, it has been tested in various types of cancer^[1]^[2]^[3]^[4] and for non-alcoholic steatohepatitis.^[5]

References

^ Falchook, Gerald; Infante, Jeffrey; Arkenau, Hendrik-Tobias; Patel, Manish R.; Dean, Emma; Borazanci, Erkut; Brenner, Andrew; Cook, Natalie; Lopez, Juanita; Pant, Shubham; Frankel, Arthur; Schmid, Peter; Moore, Kathleen; McCulloch, William; Grimmer, Katharine; O'Farrell, Marie; Kemble, George; Burris, Howard (April 2021). "First-in-human study of the safety, pharmacokinetics, and pharmacodynamics of first-in-class fatty acid synthase inhibitor TVB-2640 alone and with a taxane in advanced tumors". eClinicalMedicine. 34: 100797. doi:10.1016/j.eclinm.2021.100797. PMC 8040281. PMID 33870151.
^ Konkel, Brandon; Michalek, Joel; Diaz Duque, Enrique; Liu, Qiangia; Caflisch, Laura; Madhu, Vinu; Brenner, Andrew (11 November 2019). "Actr-45. Fatty Acid Synthase Inhibitor TVB-2640 Increases Progression Free Survival in Recurrent GBM". Neuro-Oncology. 21 (Supplement_6): vi23. doi:10.1093/neuonc/noz175.087. PMC 6847162.
^ Dean, Emma Jane; Falchook, Gerald Steven; Patel, Manish R.; Brenner, Andrew Jacob; Infante, Jeffrey R.; Arkenau, Hendrik-Tobias; Borazanci, Erkut Hasan; Lopez, Juanita Suzanne; Pant, Shubham; Schmid, Peter; Frankel, Arthur E.; Jones, Suzanne Fields; McCulloch, William; Kemble, George; O'Farrell, Marie; Burris, Howard (20 May 2016). "Preliminary activity in the first in human study of the first-in-class fatty acid synthase (FASN) inhibitor, TVB-2640". Journal of Clinical Oncology. 34 (15_suppl): 2512. doi:10.1200/JCO.2016.34.15_suppl.2512.
^ Kelly, William; Diaz Duque, Adolfo Enrique; Michalek, Joel; Konkel, Brandon; Caflisch, Laura; Chen, Yidong; Pathuri, Sarath Chand; Madhusudanannair-Kunnuparampil, Vinu; Floyd, John; Brenner, Andrew (5 July 2023). "Phase II Investigation of TVB-2640 (Denifanstat) with Bevacizumab in Patients with First Relapse High-Grade Astrocytoma". Clinical Cancer Research. 29 (13): 2419–2425. doi:10.1158/1078-0432.CCR-22-2807. PMC 10320469. PMID 37093199.
^ "CTG Labs - NCBI". clinicaltrials.gov.

[1] Falchook, Gerald; Infante, Jeffrey; Arkenau, Hendrik-Tobias; Patel, Manish R.; Dean, Emma; Borazanci, Erkut; Brenner, Andrew; Cook, Natalie; Lopez, Juanita; Pant, Shubham; Frankel, Arthur; Schmid, Peter; Moore, Kathleen; McCulloch, William; Grimmer, Katharine; O'Farrell, Marie; Kemble, George; Burris, Howard (April 2021). "First-in-human study of the safety, pharmacokinetics, and pharmacodynamics of first-in-class fatty acid synthase inhibitor TVB-2640 alone and with a taxane in advanced tumors". eClinicalMedicine. 34: 100797. doi:10.1016/j.eclinm.2021.100797. PMC 8040281. PMID 33870151.

[2] Konkel, Brandon; Michalek, Joel; Diaz Duque, Enrique; Liu, Qiangia; Caflisch, Laura; Madhu, Vinu; Brenner, Andrew (11 November 2019). "Actr-45. Fatty Acid Synthase Inhibitor TVB-2640 Increases Progression Free Survival in Recurrent GBM". Neuro-Oncology. 21 (Supplement_6): vi23. doi:10.1093/neuonc/noz175.087. PMC 6847162.

[3] Dean, Emma Jane; Falchook, Gerald Steven; Patel, Manish R.; Brenner, Andrew Jacob; Infante, Jeffrey R.; Arkenau, Hendrik-Tobias; Borazanci, Erkut Hasan; Lopez, Juanita Suzanne; Pant, Shubham; Schmid, Peter; Frankel, Arthur E.; Jones, Suzanne Fields; McCulloch, William; Kemble, George; O'Farrell, Marie; Burris, Howard (20 May 2016). "Preliminary activity in the first in human study of the first-in-class fatty acid synthase (FASN) inhibitor, TVB-2640". Journal of Clinical Oncology. 34 (15_suppl): 2512. doi:10.1200/JCO.2016.34.15_suppl.2512.

[4] Kelly, William; Diaz Duque, Adolfo Enrique; Michalek, Joel; Konkel, Brandon; Caflisch, Laura; Chen, Yidong; Pathuri, Sarath Chand; Madhusudanannair-Kunnuparampil, Vinu; Floyd, John; Brenner, Andrew (5 July 2023). "Phase II Investigation of TVB-2640 (Denifanstat) with Bevacizumab in Patients with First Relapse High-Grade Astrocytoma". Clinical Cancer Research. 29 (13): 2419–2425. doi:10.1158/1078-0432.CCR-22-2807. PMC 10320469. PMID 37093199.

[5] "CTG Labs - NCBI". clinicaltrials.gov.

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