curcumin   Click here for help

GtoPdb Ligand ID: 7000

PDB Ligand
Compound class: Natural product or derivative
Comment: Curcumin's physicochemical properties imply that it is an implausible clinical lead [30]. It is unstable, reactive, and nonbioavailable, and has been identified as having attributes of both PAINS (pan-assay interference compounds) and IMPS (invalid metabolic panaceas) compounds.
Click here for help

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.

✖

View interactive charts of activity data across species

curcumin is commercially available from our sponsors

2D Structure
Click here for help

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.

✖
Click here for structure editor
Physico-chemical Properties
Click here for help

Physico-chemical Properties

Calculated molecular properties are available for small molecules and natural products (not peptides). Properties were generated using the CDK toolkit. 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.

✖
Hydrogen bond acceptors 2
Hydrogen bond donors 2
Rotatable bonds 8
Topological polar surface area 93.06
Molecular weight 368.13
XLogP 2.95
No. Lipinski's rules broken 0
SMILES / InChI / InChIKey
Click here for help

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.

✖
Canonical SMILES COc1cc(C=CC(=O)CC(=O)C=Cc2ccc(c(c2)OC)O)ccc1O
Isomeric SMILES COc1cc(/C=C/C(=O)CC(=O)/C=C/c2ccc(c(c2)OC)O)ccc1O
InChI InChI=1S/C21H20O6/c1-26-20-11-14(5-9-18(20)24)3-7-16(22)13-17(23)8-4-15-6-10-19(25)21(12-15)27-2/h3-12,24-25H,13H2,1-2H3/b7-3+,8-4+
InChI Key VFLDPWHFBUODDF-FCXRPNKRSA-N
References
1. Anderson CM, Jevons M, Thangaraju M, Edwards N, Conlon NJ, Woods S, Ganapathy V, Thwaites DT. (2010)
Transport of the photodynamic therapy agent 5-aminolevulinic acid by distinct H+-coupled nutrient carriers coexpressed in the small intestine.
J Pharmacol Exp Ther, 332 (1): 220-8. [PMID:19789362]
2. Balasubramanyam K, Varier RA, Altaf M, Swaminathan V, Siddappa NB, Ranga U, Kundu TK. (2004)
Curcumin, a novel p300/CREB-binding protein-specific inhibitor of acetyltransferase, represses the acetylation of histone/nonhistone proteins and histone acetyltransferase-dependent chromatin transcription.
J Biol Chem, 279 (49): 51163-71. [PMID:15383533]
3. Bhardwaj RK, Herrera-Ruiz D, Sinko PJ, Gudmundsson OS, Knipp G. (2005)
Delineation of human peptide transporter 1 (hPepT1)-mediated uptake and transport of substrates with varying transporter affinities utilizing stably transfected hPepT1/Madin-Darby canine kidney clones and Caco-2 cells.
J Pharmacol Exp Ther, 314 (3): 1093-100. [PMID:15901802]
4. Boscutti G, Nardon C, Marchiò L, Crisma M, Biondi B, Dalzoppo D, Dalla Via L, Formaggio F, Casini A, Fregona D. (2018)
Anticancer Gold(III) Peptidomimetics: From Synthesis to in vitro and ex vivo Biological Evaluations.
ChemMedChem, 13 (11): 1131-1145. [PMID:29570944]
5. Cang J, Zhang J, Wang C, Liu Q, Meng Q, Wang D, Sugiyama Y, Tsuji A, Kaku T, Liu K. (2010)
Pharmacokinetics and mechanism of intestinal absorption of JBP485 in rats.
Drug Metab Pharmacokinet, 25 (5): 500-7. [PMID:20877133]
6. Cheng C, Huang DC, Zhao LY, Cao CJ, Chen GT. (2019)
Preparation and in vitro absorption studies of a novel polysaccharide‑iron (III) complex from Flammulina velutipes.
Int J Biol Macromol, 132: 801-810. [PMID:30953722]
7. Chi H, Gu Y, Xu T, Cao F. (2017)
Multifunctional organic-inorganic hybrid nanoparticles and nanosheets based on chitosan derivative and layered double hydroxide: cellular uptake mechanism and application for topical ocular drug delivery.
Int J Nanomedicine, 12: 1607-1620. [PMID:28280329]
8. Dai T, Li N, Zhang L, Zhang Y, Liu Q. (2016)
A new target ligand Ser-Glu for PEPT1-overexpressing cancer imaging.
Int J Nanomedicine, 11: 203-12. [PMID:26811678]
9. Du Y, Tian C, Wang M, Huang D, Wei W, Liu Y, Li L, Sun B, Kou L, Kan Q et al.. (2018)
Dipeptide-modified nanoparticles to facilitate oral docetaxel delivery: new insights into PepT1-mediated targeting strategy.
Drug Deliv, 25 (1): 1403-1413. [PMID:29890854]
10. Döring F, Walter J, Will J, Föcking M, Boll M, Amasheh S, Clauss W, Daniel H. (1998)
Delta-aminolevulinic acid transport by intestinal and renal peptide transporters and its physiological and clinical implications.
J Clin Invest, 101 (12): 2761-7. [PMID:9637710]
11. Foley DW, Pathak RB, Phillips TR, Wilson GL, Bailey PD, Pieri M, Senan A, Meredith D. (2018)
Thiodipeptides targeting the intestinal oligopeptide transporter as a general approach to improving oral drug delivery.
Eur J Med Chem, 156: 180-189. [PMID:30006163]
12. Geissler S, Hellwig M, Zwarg M, Markwardt F, Henle T, Brandsch M. (2010)
Transport of the advanced glycation end products alanylpyrraline and pyrralylalanine by the human proton-coupled peptide transporter hPEPT1.
J Agric Food Chem, 58 (4): 2543-7. [PMID:20104847]
13. Gong Y, Wu X, Wang T, Zhao J, Liu X, Yao Z, Zhang Q, Jian X. (2017)
Targeting PEPT1: a novel strategy to improve the antitumor efficacy of doxorubicin in human hepatocellular carcinoma therapy.
Oncotarget, 8 (25): 40454-40468. [PMID:28465466]
14. Gourdon B, Chemin C, Moreau A, Arnauld T, Baumy P, Cisternino S, Péan JM, Declèves X. (2017)
Functionalized PLA-PEG nanoparticles targeting intestinal transporter PepT1 for oral delivery of acyclovir.
Int J Pharm, 529 (1-2): 357-370. [PMID:28705621]
15. Gourdon B, Chemin C, Moreau A, Arnauld T, Delbos JM, Péan JM, Declèves X. (2018)
Influence of PLA-PEG nanoparticles manufacturing process on intestinal transporter PepT1 targeting and oxytocin transport.
Eur J Pharm Biopharm, 129: 122-133. [PMID:29803721]
16. Gu Y, Xu C, Wang Y, Zhou X, Fang L, Cao F. (2019)
Multifunctional Nanocomposites Based on Liposomes and Layered Double Hydroxides Conjugated with Glycylsarcosine for Efficient Topical Drug Delivery to the Posterior Segment of the Eye.
Mol Pharm, 16 (7): 2845-2857. [PMID:31244219]
17. Gupta D, Varghese Gupta S, Dahan A, Tsume Y, Hilfinger J, Lee KD, Amidon GL. (2013)
Increasing oral absorption of polar neuraminidase inhibitors: a prodrug transporter approach applied to oseltamivir analogue.
Mol Pharm, 10 (2): 512-22. [PMID:23244438]
18. Gupta SV, Gupta D, Sun J, Dahan A, Tsume Y, Hilfinger J, Lee KD, Amidon GL. (2011)
Enhancing the intestinal membrane permeability of zanamivir: a carrier mediated prodrug approach.
Mol Pharm, 8 (6): 2358-67. [PMID:21905667]
19. Hellwig M, Geissler S, Matthes R, Peto A, Silow C, Brandsch M, Henle T. (2011)
Transport of free and peptide-bound glycated amino acids: synthesis, transepithelial flux at Caco-2 cell monolayers, and interaction with apical membrane transport proteins.
Chembiochem, 12 (8): 1270-9. [PMID:21538757]
20. Incecayir T, Sun J, Tsume Y, Xu H, Gose T, Nakanishi T, Tamai I, Hilfinger J, Lipka E, Amidon GL. (2016)
Carrier-Mediated Prodrug Uptake to Improve the Oral Bioavailability of Polar Drugs: An Application to an Oseltamivir Analogue.
J Pharm Sci, 105 (2): 925-934. [PMID:26869437]
21. Jiang Q, Zhang J, Tong P, Gao Y, Lv Y, Wang C, Luo M, Sun M, Wang J, Feng Y et al.. (2019)
Bioactivatable Pseudotripeptidization of Cyclic Dipeptides To Increase the Affinity toward Oligopeptide Transporter 1 for Enhanced Oral Absorption: An Application to Cyclo(l-Hyp-l-Ser) (JBP485).
J Med Chem, 62 (17): 7708-7721. [PMID:31393124]
22. Jin Y, Liu Q, Zhou C, Hu X, Wang L, Han S, Zhou Y, Liu Y. (2019)
Intestinal oligopeptide transporter PepT1-targeted polymeric micelles for further enhancing the oral absorption of water-insoluble agents.
Nanoscale, 11 (44): 21433-21448. [PMID:31681915]
23. Knütter I, Theis S, Hartrodt B, Born I, Brandsch M, Daniel H, Neubert K. (2001)
A novel inhibitor of the mammalian peptide transporter PEPT1.
Biochemistry, 40 (14): 4454-8. [PMID:11284702]
24. Landowski CP, Song X, Lorenzi PL, Hilfinger JM, Amidon GL. (2005)
Floxuridine amino acid ester prodrugs: enhancing Caco-2 permeability and resistance to glycosidic bond metabolism.
Pharm Res, 22 (9): 1510-8. [PMID:16132363]
25. Landowski CP, Vig BS, Song X, Amidon GL. (2005)
Targeted delivery to PEPT1-overexpressing cells: acidic, basic, and secondary floxuridine amino acid ester prodrugs.
Mol Cancer Ther, 4 (4): 659-67. [PMID:15827340]
26. Li T, Wu D, Yang Y, Xiao T, Han Y, Li J, Liu T, Li L, Dai Z, Li Y et al.. (2020)
Synthesis, pharmacological evaluation and mechanistic study of scutellarin methyl ester -4'-dipeptide conjugates for the treatment of hypoxic-ischemic encephalopathy (HIE) in rat pups.
Bioorg Chem, 101: 103980. [PMID:32540782]
27. Liu Z, Wang C, Liu Q, Meng Q, Cang J, Mei L, Kaku T, Liu K. (2011)
Uptake, transport and regulation of JBP485 by PEPT1 in vitro and in vivo.
Peptides, 32 (4): 747-54. [PMID:21262302]
28. Miyabe J, Ohgaki R, Saito K, Wei L, Quan L, Jin C, Liu X, Okuda S, Nagamori S, Ohki H et al.. (2019)
Boron delivery for boron neutron capture therapy targeting a cancer-upregulated oligopeptide transporter.
J Pharmacol Sci, 139 (3): 215-222. [PMID:30833090]
29. Miyake M, Fujishima M, Nakai D. (2017)
Inhibitory Potency of Marketed Drugs for Ulcerative Colitis and Crohn's Disease on PEPT1.
Biol Pharm Bull, 40 (9): 1572-1575. [PMID:28867741]
30. Nelson KM, Dahlin JL, Bisson J, Graham J, Pauli GF, Walters MA. (2017)
The Essential Medicinal Chemistry of Curcumin.
J Med Chem, 60 (5): 1620-1637. [PMID:28074653]
31. Sawada K, Terada T, Saito H, Hashimoto Y, Inui K. (1999)
Effects of glibenclamide on glycylsarcosine transport by the rat peptide transporters PEPT1 and PEPT2.
Br J Pharmacol, 128 (6): 1159-64. [PMID:10578127]
32. Shao J, Han J, Zhu Y, Mao A, Wang Z, Zhang K, Zhang X, Zhang Y, Tang C, Ma X. (2019)
Curcumin Induces Endothelium-Dependent Relaxation by Activating Endothelial TRPV4 Channels.
J Cardiovasc Transl Res, 12 (6): 600-607. [PMID:31664615]
33. Song X, Lorenzi PL, Landowski CP, Vig BS, Hilfinger JM, Amidon GL. (2005)
Amino acid ester prodrugs of the anticancer agent gemcitabine: synthesis, bioconversion, metabolic bioevasion, and hPEPT1-mediated transport.
Mol Pharm, 2 (2): 157-67. [PMID:15804190]
34. Sun Y, Gan W, Lei M, Jiang W, Cheng M, He J, Sun Q, Liu W, Hu L, Jin Y. (2018)
PEPT1-mediated prodrug strategy for oral delivery of peramivir.
Asian J Pharm Sci, 13 (6): 555-565. [PMID:32104429]
35. Tamai I, Nakanishi T, Nakahara H, Sai Y, Ganapathy V, Leibach FH, Tsuji A. (1998)
Improvement of L-dopa absorption by dipeptidyl derivation, utilizing peptide transporter PepT1.
J Pharm Sci, 87 (12): 1542-6. [PMID:10189264]
36. Tao W, Zhao D, Sun M, Li M, Zhang X, He Z, Sun Y, Sun J. (2017)
Enzymatic activation of double-targeted 5'-O-L-valyl-decitabine prodrug by biphenyl hydrolase-like protein and its molecular design basis.
Drug Deliv Transl Res, 7 (2): 304-311. [PMID:28070705]
37. Tao W, Zhao D, Sun M, Wang Z, Lin B, Bao Y, Li Y, He Z, Sun Y, Sun J. (2018)
Intestinal absorption and activation of decitabine amino acid ester prodrugs mediated by peptide transporter PEPT1 and enterocyte enzymes.
Int J Pharm, 541 (1-2): 64-71. [PMID:29471144]
38. Terada T, Sawada K, Saito H, Hashimoto Y, Inui K. (2000)
Inhibitory effect of novel oral hypoglycemic agent nateglinide (AY4166) on peptide transporters PEPT1 and PEPT2.
Eur J Pharmacol, 392 (1-2): 11-7. [PMID:10748266]
39. Thompson BR, Shi J, Zhu HJ, Smith DE. (2020)
Pharmacokinetics of gemcitabine and its amino acid ester prodrug following intravenous and oral administrations in mice.
Biochem Pharmacol, 180: 114127. [PMID:32603666]
40. Tsuji A. (1999)
Tissue selective drug delivery utilizing carrier-mediated transport systems.
J Control Release, 62 (1-2): 239-44. [PMID:10518656]
41. Tsume Y, Hilfinger JM, Amidon GL. (2008)
Enhanced cancer cell growth inhibition by dipeptide prodrugs of floxuridine: increased transporter affinity and metabolic stability.
Mol Pharm, 5 (5): 717-27. [PMID:18652477]
42. Tsume Y, Vig BS, Sun J, Landowski CP, Hilfinger JM, Ramachandran C, Amidon GL. (2008)
Enhanced absorption and growth inhibition with amino acid monoester prodrugs of floxuridine by targeting hPEPT1 transporters.
Molecules, 13 (7): 1441-54. [PMID:18719516]
43. Wang CL, Fan YB, Lu HH, Tsai TH, Tsai MC, Wang HP. (2010)
Evidence of D-phenylglycine as delivering tool for improving L-dopa absorption.
J Biomed Sci, 17: 71. [PMID:20815935]
44. Wang J, Wang L, Li Y, Wang X, Tu P. (2018)
Apically targeted oral micelles exhibit highly efficient intestinal uptake and oral absorption.
Int J Nanomedicine, 13: 7997-8012. [PMID:30538473]
45. Wang Y, Zhou L, Fang L, Cao F. (2020)
Multifunctional carboxymethyl chitosan derivatives-layered double hydroxide hybrid nanocomposites for efficient drug delivery to the posterior segment of the eye.
Acta Biomater, 104: 104-114. [PMID:31931169]
46. Wu H, Xu Y, Cai M, You L, Liu J, Dong X, Yin X, Ni J, Qu C. (2022)
Design of an L-Valine-Modified Nanomicelle-Based Drug Delivery System for Overcoming Ocular Surface Barriers.
Pharmaceutics, 14 (6). [PMID:35745853]
47. Wu Q, He X, Zhou S, Shi F, Lu Y. (2020)
Role of PEPT1in the transport of cinnabar in Caco-2 cells.
Toxicol In Vitro, 63: 104747. [PMID:31838184]
48. Wu Y, Sun M, Wang D, Li G, Huang J, Tan S, Bao L, Li Q, Li G, Si L. (2019)
A PepT1 mediated medicinal nano-system for targeted delivery of cyclosporine A to alleviate acute severe ulcerative colitis.
Biomater Sci, 7 (10): 4299-4309. [PMID:31408067]
49. Xu T, Xu X, Gu Y, Fang L, Cao F. (2018)
Functional intercalated nanocomposites with chitosan-glutathione-glycylsarcosine and layered double hydroxides for topical ocular drug delivery.
Int J Nanomedicine, 13: 917-937. [PMID:29491707]
50. Xu T, Zhang J, Chi H, Cao F. (2016)
Multifunctional properties of organic-inorganic hybrid nanocomposites based on chitosan derivatives and layered double hydroxides for ocular drug delivery.
Acta Biomater, 36: 152-63. [PMID:26940970]
51. Xu X, Sun L, Zhou L, Cheng Y, Cao F. (2020)
Functional chitosan oligosaccharide nanomicelles for topical ocular drug delivery of dexamethasone.
Carbohydr Polym, 227: 115356. [PMID:31590850]
52. Yan Z, Sun J, Chang Y, Liu Y, Fu Q, Xu Y, Sun Y, Pu X, Zhang Y, Jing Y et al.. (2011)
Bifunctional peptidomimetic prodrugs of didanosine for improved intestinal permeability and enhanced acidic stability: synthesis, transepithelial transport, chemical stability and pharmacokinetics.
Mol Pharm, 8 (2): 319-29. [PMID:21280612]
53. Yuri T, Kono Y, Okada T, Terada T, Miyauchi S, Fujita T. (2020)
Transport Characteristics of 5-Aminosalicylic Acid Derivatives Conjugated with Amino Acids via Human H+-Coupled Oligopeptide Transporter PEPT1.
Biol Pharm Bull, 43 (4): 697-706. [PMID:32238712]
54. Zhang J, Wen H, Shen F, Wang X, Shan C, Chai C, Liu J, Li W. (2019)
Synthesis and biological evaluation of a novel series of curcumin-peptide derivatives as PepT1-mediated transport drugs.
Bioorg Chem, 92: 103163. [PMID:31450166]