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Lac-Phe   Click here for help

GtoPdb Ligand ID: 14494

Synonyms: Lactoyl Phenylalanine | N-L-lactoyl-Phe | N-Lactoyl-Phe | N-lactoyl-phenylalanine
Compound class: Synthetic organic
Comment: Lac-Phe (N-lactoyl-phenylalanine) is a metabolite of lactate [5]. Its biosynthesis is catalyzed by carnosine dipeptidase 2 (CNDP2), principally in intestinal epithelial cells. Emerging evidence suggests that Lac-Phe impacts upon neurobiological processes, and represents a previously unidentified exercise-induced factor (exerkine) with appetite-regulating (anorexigenic) activity [1-2].

Interestingly, treatment with the insulin-sensitizing drug metformin elevates Lac-Phe, which may partially explain the drug's metabolic, weight-regulating benefits [3-4,6].
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 5
Hydrogen bond donors 3
Rotatable bonds 6
Topological polar surface area 86.63
Molecular weight 237.25
XLogP 0.36
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 C[C@@H](C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)O)O
Isomeric SMILES C[C@@H](C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)O)O
InChI InChI=1S/C12H15NO4/c1-8(14)11(15)13-10(12(16)17)7-9-5-3-2-4-6-9/h2-6,8,10,14H,7H2,1H3,(H,13,15)(H,16,17)/t8-,10-/m0/s1
InChI Key IIRJJZHHNGABMQ-WPRPVWTQSA-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. Bilusic M, Gannamedi DP, Challu B, Ferdous S, Mateo-Victoriano B, Pokharel S, Bayik D, Sharma J, Lombard DB, Rai P. (2026)
The anti-obesogenic metabolite, Lac-Phe, is elevated by metformin treatment in prostate cancer patients.
EMBO Mol Med, 18 (5): 1551-1562. [PMID:41942753]
2. Oni OP, Scott B, Schwartz LC, MacCormack TJ, Hankir M, Rourke JL. (2026)
Beyond exercise and appetite: The expanding biology and therapeutic potential of N-lactoyl-phenylalanine.
J Pharmacol Exp Ther, 393 (2): 103798. [PMID:41547294]
3. Scott B, Day EA, O'Brien KL, Scanlan J, Cromwell G, Scannail AN, McDonnell ME, Finlay DK, Lynch L. (2024)
Metformin and feeding increase levels of the appetite-suppressing metabolite Lac-Phe in humans.
Nat Metab, 6 (4): 651-658. [PMID:38499765]
4. Starling S. (2024)
Metformin acts through appetite-suppressing metabolite: Lac-Phe.
Nat Rev Endocrinol, 20 (6): 319. [PMID:38565678]
5. Wang N, Zhang J, Zhang X, Xuan D. (2026)
Lac-Phe: An Emerging Appetite-Regulating Exerkine with Health and Therapeutic Benefits.
Curr Obes Rep, 15 (1): 4. [PMID:41504957]
6. Xiao S, Li VL, Lyu X, Chen X, Wei W, Abbasi F, Knowles JW, Tung AS, Deng S, Tiwari G et al.. (2024)
Lac-Phe mediates the effects of metformin on food intake and body weight.
Nat Metab, 6 (4): 659-669. [PMID:38499766]