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denifanstat   Click here for help

GtoPdb Ligand ID: 14123

Synonyms: ASC-40 | ASC40 | compound 152 [US8871790] | TVB-2640 | TVB2640
PDB Ligand
Compound class: Synthetic organic
Comment: Denifanstat (TVB-2640, ASC-40) is a fatty acid synthase inhibitor [1,3]. It was designed to reduce excess liver fat and directly inhibit inflammatory and fibrogenic pathways in fatty-liver diseases [2]. Targeting fatty acid synthase has also been investigated for addition to chemotherapeutic regimens [4-7], and for potential to reduce sebum overproduction and inflammation in severe acne.
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Ligand Activity Visualisation Charts

These are box plot that provide a unique visualisation, summarising all the activity data for a ligand taken from ChEMBL and GtoPdb across multiple targets and species. Click on a plot to see the median, interquartile range, low and high data points. A value of zero indicates that no data are available. A separate chart is created for each target, and where possible the algorithm tries to merge ChEMBL and GtoPdb targets by matching them on name and UniProt accession, for each available species. However, please note that inconsistency in naming of targets may lead to data for the same target being reported across multiple charts.

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View interactive charts of activity data across species
2D Structure
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2D Structure

An image of the ligand's 2D structure. For small molecules with SMILES these are drawn using the NCI/CADD Chemical Identifier Resolver. Click on the image to access the chemical structure search tool with the ligand pre-loaded in the structure editor. For other types of ligands, e.g. longer nucleotides and peptides, a manually drawn representation of the molecule may be provided.

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Physico-chemical Properties
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Physico-chemical Properties

Calculated molecular properties are available for small molecules and natural products (not peptides). Properties were generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/). All properties were selected to enable the prediction of the Lipinski Rule-of-Five profile or ‘druglikeness’ for each ligand. For more info on each category see the help pages.

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Hydrogen bond acceptors 6
Hydrogen bond donors 1
Rotatable bonds 5
Topological polar surface area 80.85
Molecular weight 439.55
XLogP 4.07
No. Lipinski's rules broken 0

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
SMILES / InChI / InChIKey
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SMILES / InChI / InChIKey

SMILES (Simplified Molecular Input Line Entry Specification) A specification for unambiguously describing the structure of chemical molecules using short ASCII strings. Canonical SMILES specify a unique representation of the 2D structure without chiral or isotopic specifications. Isomeric SMILES include chiral specification and isotopes.

Standard InChI (IUPAC International Chemical Identifier) and InChIKey InChI is a non-proprietary, standard, textual identifier for chemical substances designed to facilitate linking of information and database searching. An InChIKey is a simplified version of a full InChI, designed for easier web searching.

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)

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Canonical SMILES CC1=C(C=C(C(=C1)C2CCC2)C3=NNC(=N3)C)C(=O)N4CCC(CC4)C5=CC=C(C=C5)C#N
Isomeric 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)
InChI Key BBGOSBDSLYHMRA-UHFFFAOYSA-N

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
References
1. Hasan SMN, Lou JW, Keszei AFA, Dai DL, Mazhab-Jafari MT. (2023)
Atomic model for core modifying region of human fatty acid synthase in complex with Denifanstat.
Nat Commun, 14 (1): 3460. [PMID:37308485]
2. Loomba R, Mohseni R, Lucas KJ, Gutierrez JA, Perry RG, Trotter JF, Rahimi RS, Harrison SA, Ajmera V, Wayne JD et al.. (2021)
TVB-2640 (FASN Inhibitor) for the Treatment of Nonalcoholic Steatohepatitis: FASCINATE-1, a Randomized, Placebo-Controlled Phase 2a Trial.
Gastroenterology, 161 (5): 1475-1486. [PMID:34310978]
3. Oslob JD, McDowell RS, Johnson R, Yang H, Evanchik M, Zaharia CA, Cai H, Hu LW. (2014)
Heterocyclic modulators of lipid synthesis.
Patent number: US8871790B2. Assignee: Sagimet Biosciences Inc. Priority date: 08/03/2012. Publication date: 28/10/2014.
4. Serhan HA, Bao L, Cheng X, Qin Z, Liu CJ, Heth JA, Udager AM, Soellner MB, Merajver SD, Morikawa A et al.. (2024)
Targeting fatty acid synthase in preclinical models of TNBC brain metastases synergizes with SN-38 and impairs invasion.
NPJ Breast Cancer, 10 (1): 43. [PMID:38858374]
5. Steen TV, Espinoza I, Duran C, Casadevall G, Serrano-Hervás E, Cuyàs E, Verdura S, Kemble G, Kaufmann SH, McWilliams R et al.. (2025)
Fatty acid synthase (FASN) inhibition cooperates with BH3 mimetic drugs to overcome resistance to mitochondrial apoptosis in pancreatic cancer.
Neoplasia, 62: 101143. [PMID:39999714]
6. Wang X, Du Q, Mai Q, Zou Q, Wang S, Lin X, Chen Q, Wei M, Chi C, Peng Z et al.. (2025)
Targeting FASN enhances cisplatin sensitivity via SLC7A11-mediated ferroptosis in cervical cancer.
Transl Oncol, 56: 102396. [PMID:40239242]
7. Ward AV, Riley D, Cosper KE, Finlay-Schultz J, Brechbuhl HM, Libby AE, Hill KB, Varshney RR, Kabos P, Rudolph MC et al.. (2024)
Lipid metabolic reprogramming drives triglyceride storage and variable sensitivity to FASN inhibition in endocrine-resistant breast cancer cells.
bioRxiv,. [PMID:38895323]