CAFFEIC ACID

Possibly Marketed Outside US

First approved in 2018

Details

Stereochemistry	ACHIRAL
Molecular Formula	C9H8O4
Molecular Weight	180.1574
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	1
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

OC(=O)\C=C\C1=CC=C(O)C(O)=C1

InChI

InChIKey=QAIPRVGONGVQAS-DUXPYHPUSA-N

InChI=1S/C9H8O4/c10-7-3-1-6(5-8(7)11)2-4-9(12)13/h1-5,10-11H,(H,12,13)/b4-2+

HIDE SMILES / InChI

Molecular Formula	C9H8O4
Molecular Weight	180.1574
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	1
Optical Activity	NONE

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/21116690 | https://www.ncbi.nlm.nih.gov/pubmed/25498895 | https://www.ncbi.nlm.nih.gov/pubmed/25778883 | https://www.ncbi.nlm.nih.gov/pubmed/28911606

Caffeic acid is an organic compound that is classified as a hydroxycinnamic acid. Caffeic acid is naturally found in many agricultural products, such as fruit, vegetables, wine, olive oil, and coffee, and therefore, significantly present in human diet. Caffeic acid has been reported to have a wide variety of biological activities, including antioxidants, antithrombosis, antihypertensive, antifibrosis, antiviral and anti-tumor properties. Caffeic acid can be effectively employed as a natural antioxidant in various food products such as oils. Caffeic acid exhibits potent anticancer effect in HT-1080 cell line and that it may be used as an anticancer agent. Caffeic acid showed neuroprotective action against oxidative and DNA damage produced in the kindling epilepsy model, although they did not produce antiepileptogenic effect in vivo. Caffeic acid was effective in patients with primary immune thrombocytopenia. Detected in clinical trial caffeic acid-related adverse events were: mild nausea and elevation of liver enzymes.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Apoptosis 156 Target ID: WP254 Sources: https://www.ncbi.nlm.nih.gov/pubmed/21116690	Activator 1447
Oxidative Stress 162 Target ID: WP408 Sources: https://www.ncbi.nlm.nih.gov/pubmed/25498895 \| https://www.ncbi.nlm.nih.gov/pubmed/26098639 \| https://www.ncbi.nlm.nih.gov/pubmed/28911606	Inhibitor 8504

Conditions

Condition	Modality	Highest Phase	Product
Fibrosarcoma 4 Sources: https://www.ncbi.nlm.nih.gov/pubmed/21116690	Primary	Basic research	Unknown Approved Use Unknown
Esophageal cancer 12 Sources: https://clinicaltrials.gov/ct2/show/NCT03070262	Primary	Phase III 665	Unknown Approved Use Unknown
Immune thrombocytopenia 10 Sources: https://www.ncbi.nlm.nih.gov/pubmed/25778883 https://clinicaltrials.gov/ct2/show/NCT02556814 https://clinicaltrials.gov/ct2/show/NCT02351622	Primary	Phase IV 63	Unknown Approved Use Unknown

C_max

Value	Dose	Co-administered	Analyte	Population
11.24 μM EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/15941309/	100 μmol/kg single, intragastric dose: 100 μmol/kg route of administration: Intragastric experiment type: SINGLE co-administered:		CAFFEIC ACID serum	Rattus norvegicus population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
34.8 μM × min EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/15941309/	100 μmol/kg single, intragastric dose: 100 μmol/kg route of administration: Intragastric experiment type: SINGLE co-administered:		CAFFEIC ACID serum	Rattus norvegicus population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
34.8 min EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/15941309/	100 μmol/kg single, intragastric dose: 100 μmol/kg route of administration: Intragastric experiment type: SINGLE co-administered:		CAFFEIC ACID serum	Rattus norvegicus population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
activator 150 inhibitor 2252	inhibitor 2438	inhibitor 2507	inhibitor 2217

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
BCRP 910 CYP19A1 429 OATP1B1 1079 OAT3 747 P-gp 1741 CYP1A2 2153 OATP1B3 961 MRP1 116 CYP2C19 2057 OAT1 725	SULT1A3 31 UGT2B15 236 UGT1A3 470 UGT1A4 399 UGT1A9 423 UGT2B17 237 UGT2B7 456 UGT2B4 278 SULT1E1 22 SULT1C3 1 SULT1A2 3 SULT1C2 3 UGT1A10 331 UGT1A6 343 SULT1A1 37 SULT1B1 8 UGT1A7 249 UGT1A8 323 SULT2A1 28 SULT2B1b 2 SULT4A1 1 SULT6B1 1 UGT1A1 479	BCRP 101 MRP2 146 P-gp 301

Drug as perpetrator

Target	Modality	Activity
BCRP 985	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/compound/689043#section=Biological-Test-Results Page: 130.0	no
CYP19A1 430	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/compound/689043#section=Biological-Test-Results Page: 482.0	no
CYP3A4 2633	activator 342 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwzNDAiLCJ1c2VfY3VzdG9tX3F1ZXJ5Ijp0cnVlLCJzZWFyY2hfdGVybSI6IiIsInRleHRfZmlsdGVyIjoiQ0hFTUJMMTQ1In19	no
MRP1 232	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/compound/689043#section=Biological-Test-Results Page: 106.0	no
MRP2 625	inducer 1966 Sources: https://pubmed.ncbi.nlm.nih.gov/25399682/	no
CYP2C19 2141	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/25196644/	weak [IC50 >100 uM]
CYP3A4 2633	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/25196644/	weak [IC50 >100 uM]
CYP2C9 2497	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/25196644/	yes [IC50 1.01 uM]
CYP1A2 2333	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/25196644/	yes [IC50 1.25 uM]
CYP2D6 2546	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/25196644/	yes [IC50 1.45 uM]
OAT1 730	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/21697612/	yes [IC50 16.6 uM]
OAT3 749	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/21697612/	yes [IC50 5.4 uM]
OATP1B1 1095	inhibitor 4027 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwxNjk3NjY4IiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDE0NSJ9fQ==	yes [Inhibition 10 uM]
OATP1B3 970	inhibitor 4027 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwxNzQzMTIxIiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDE0NSJ9fQ==	yes [Inhibition 10 uM]
P-gp 1932	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/31936160/	yes [Ki 14.13 uM]
BCRP 985	inducer 1966 Sources: https://pubmed.ncbi.nlm.nih.gov/25399682/	yes
P-gp 1932	inducer 1966 Sources: https://pubmed.ncbi.nlm.nih.gov/25399682/	yes

Drug as victim

Target	Modality	Activity
SULT1A1 37	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/19954949/	major [Km 11.6 uM]
UGT1A9 423	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/19954949/	major [Km 1900 uM]
UGT1A1 479	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/19954949/	minor [Km 4240 uM]
SULT1A3 31	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/19954949/	minor
SULT1C2 3	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/19954949/	no
SULT1C3 1	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/19954949/	no
SULT2A1 28	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/19954949/	no
SULT2B1b 2	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/19954949/	no
SULT4A1 1	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/19954949/	no
SULT6B1 1	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/19954949/	no
UGT1A10 331	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/19954949/	no
UGT1A4 399	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/19954949/	no
UGT1A7 249	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/19954949/	no
UGT2B15 236	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/19954949/	no
UGT2B17 237	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/19954949/	no
UGT2B4 278	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/19954949/	no
SULT1A2 3	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/19954949/	weak
SULT1B1 8	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/19954949/	weak
SULT1E1 22	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/19954949/	weak
UGT1A3 470	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/19954949/	weak
UGT1A6 343	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/19954949/	weak
UGT1A8 323	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/19954949/	weak
UGT2B7 456	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/19954949/	weak

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 2263	inhibitor 2237 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwyNDAiLCJ1c2VfY3VzdG9tX3F1ZXJ5Ijp0cnVlLCJzZWFyY2hfdGVybSI6IiIsInRleHRfZmlsdGVyIjoiQ0hFTUJMMTQ1In19

PubMed

Title	Date	PubMed
Protective effects of caffeic acid against hypothalamic neuropeptides alterations induced by malathion in rat.	2015-04	25404496
Investigation of the effects of some phenolic compounds on the activities of glucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase from human erythrocytes.	2014-11	25130191
Polyacetylenes and anti-hepatitis B virus active constituents from Artemisia capillaris.	2014-06	24685503
Activity of caffeic acid derivatives against Candida albicans biofilm.	2014-03-15	24582984
Inhibitors of the glyoxylate cycle enzyme ICL1 in Candida albicans for potential use as antifungal agents.	2014	24781056
Differentiation between stoichiometric and anticatalytic antioxidant properties of benzoic acid analogues: a structure/redox potential relationship study.	2013-11-25	24060682
Antifungal efficacy of some natural phenolic compounds against significant pathogenic and toxinogenic filamentous fungi.	2013-10	23800587
Oral administration of caffeic acid ameliorates the effect of cisplatin on brush border membrane enzymes and antioxidant system in rat intestine.	2013-01	21640567
Inhibitory effects of caffeic acid phenethyl ester derivatives on replication of hepatitis C virus.	2013	24358168
Novel phenolic inhibitors of small/intermediate-conductance Ca²⁺-activated K⁺ channels, KCa3.1 and KCa2.3.	2013	23516517
Design, synthesis, and molecular hybrids of caudatin and cinnamic acids as novel anti-hepatitis B virus agents.	2012-08	22687441
Caffeic acid attenuates 12-O-tetradecanoyl-phorbol-13-acetate (TPA)-induced NF-κB and COX-2 expression in mouse skin: abrogation of oxidative stress, inflammatory responses and proinflammatory cytokine production.	2012-02	22036979
Interaction of cinnamic acid derivatives with commercial hypoglycemic drugs on 2-deoxyglucose uptake in 3T3-L1 adipocytes.	2011-09-28	21870829
Protective effects of caffeic acid on lactate dehydrogenase isoenzymes, electrocardiogram, adenosine triphosphatases, and hematology on isoproterenol-induced myocardial infarcted rats.	2011-04-08	21472895
Caffeic acid protects rat heart mitochondria against isoproterenol-induced oxidative damage.	2010-11	20376586
Biochemical mechanism of caffeic acid phenylethyl ester (CAPE) selective toxicity towards melanoma cell lines.	2010-10-06	20685355
Entacapone and tolcapone, two catechol O-methyltransferase inhibitors, block fibril formation of alpha-synuclein and beta-amyloid and protect against amyloid-induced toxicity.	2010-05-14	20150427
Preventive effect of caffeic acid on lysosomal dysfunction in isoproterenol-induced myocardial infarcted rats.	2010-04-15	20391626
The genome-wide expression profile of Scrophularia ningpoensis-treated thapsigargin-stimulated U-87MG cells.	2009-05	19442820
Oxygen-glucose deprivation activates 5-lipoxygenase mediated by oxidative stress through the p38 mitogen-activated protein kinase pathway in PC12 cells.	2009-03	18951527
Synthesis of trans-caffeate analogues and their bioactivities against HIV-1 integrase and cancer cell lines.	2008-12-15	18952420
Efficacy of caffeic acid in preventing nickel induced oxidative damage in liver of rats.	2008-05-28	18405891
Protection of mouse brain from aluminum-induced damage by caffeic acid.	2008	18482095
Novel screening assay for antioxidant protection against peroxyl radical-induced loss of protein function.	2007-11	17705259
Transcriptional regulation of deoxynivalenol-induced IL-8 expression in human monocytes.	2007-10	17636245
Cigarette smoke toxicants as substrates and inhibitors for human cytosolic SULTs.	2007-05-15	17433394
Anti-inflammatory and anti-atherogenic effects of cathechin, caffeic acid and trans-resveratrol in apolipoprotein E deficient mice.	2007-04	16806235
Prediction of estrogen receptor agonists and characterization of associated molecular descriptors by statistical learning methods.	2006-11	16497524
Urinary flavonoids and phenolic acids as biomarkers of intake for polyphenol-rich foods.	2006-07	16870009
Activation of rat liver microsomal glutathione S-transferase by gallic acid.	2005-11-19	16125204
A blend of polyphenolic compounds explains the stimulatory effect of red wine on human endothelial NO synthase.	2005-03	15740983
Anti-HIV activities of natural antioxidant caffeic acid derivatives: toward an antiviral supplementation diet.	2005	16029149
The histone deacetylase inhibitor suberoylanilide hydroxamic acid induces apoptosis via induction of 15-lipoxygenase-1 in colorectal cancer cells.	2004-12-01	15574791
Gastrointestinally distributed UDP-glucuronosyltransferase 1A10, which metabolizes estrogens and nonsteroidal anti-inflammatory drugs, depends upon phosphorylation.	2004-07-02	15117964
Protective effect of Mesona procumbens against tert-butyl hydroperoxide-induced acute hepatic damage in rats.	2004-06-30	15212457
Isolation, structure, and HIV-1-integrase inhibitory activity of structurally diverse fungal metabolites.	2003-12	14714192
Antiviral activity of Plantago major extracts and related compounds in vitro.	2002-07	12076751
In vitro activity of polyhydroxycarboxylates against herpesviruses and HIV.	2001-11	12018678
Do wine polyphenols modulate p53 gene expression in human cancer cell lines?	2001-07	11522280
Nonsteroidal anti-inflammatory drugs induce apoptosis in esophageal cancer cells by restoring 15-lipoxygenase-1 expression.	2001-06-15	11406566
Structure-activity relationships: analogues of the dicaffeoylquinic and dicaffeoyltartaric acids as potent inhibitors of human immunodeficiency virus type 1 integrase and replication.	1999-02-11	9986720
Dicaffeoylquinic and dicaffeoyltartaric acids are selective inhibitors of human immunodeficiency virus type 1 integrase.	1998-01	9449274
Dicaffeoylquinic acid inhibitors of human immunodeficiency virus integrase: inhibition of the core catalytic domain of human immunodeficiency virus integrase.	1996-10	8863829
Inhibitors of HIV-1 replication [corrected; erratum to be published] that inhibit HIV integrase.	1996-06-25	8692814
Molecular mechanisms of tirapazamine (SR 4233, Win 59075)-induced hepatocyte toxicity under low oxygen concentrations.	1995-04	7710944
In vitro and in vivo reversible and irreversible inhibition of rat glutathione S-transferase isoenzymes by caffeic acid and its 2-S-glutathionyl conjugate.	1993-07	8340025
Inhibition of HIV-1 proteinase by non-peptide carboxylates.	1991-04-15	2018518
Selective inhibitory activity of polyhydroxycarboxylates derived from phenolic compounds against human immunodeficiency virus replication.	1991	1675677
Inhibition of HIV replication by Hyssop officinalis extracts.	1990-12	1708226
Influence of twenty potentially antiviral substances on in vitro multiplication of hepatitis A virus.	1986-03	3010855

Patents

Sample Use Guides

In Vivo Use Guide

300mg three times a day

Route of Administration: Oral

In Vitro Use Guide

Caffeic acid treatment significantly increased ROS level in HT-1080 cells. Among all the doses tested, 50 ug/ml of Caffeic acid showed the maximum generation of ROS (95%) in HT-1080 cells.

Substance Class	Chemical Created by `admin` on `Mon Mar 31 18:47:47 GMT 2025` Edited by `admin` on `Mon Mar 31 18:47:47 GMT 2025`
Record UNII	U2S3A33KVM
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

2-PROPENOIC ACID, 3-(3,4-DIHYDROXYPHENYL)-, (2E)-

Preferred Name

English

CAFFEIC ACID

Official Name

English

3,4-DIHYDROXYBENZENEACRYLIC ACID

Systematic Name

English

CAFFEIC ACID [DSC]

Common Name

English

4-(2-CARBOXYETHENYL)-1,2-DIHYDROXYBENZENE

Systematic Name

English

CAFFEIC ACID (CONSTITUENT OF BLACK COHOSH) [DSC]

Common Name

English

Caffeic acid [WHO-DD]

Common Name

English

3-(3,4-DIHYDROXYPHENYL)-2-PROPENOIC ACID

Systematic Name

English

CAFFEIC ACID [IARC]

Common Name

English

CINNAMIC ACID, 3,4-DIHYDROXY-

Common Name

English

CAFFEIC ACID [HSDB]

Common Name

English

NSC-57197

Code

English

NSC-623438

Code

English

CAFFEIC ACID [MI]

Common Name

English

TRANS-3,4-DIHYDROXYCINNAMIC ACID

Common Name

English

TRANS-CAFFEIC ACID

Common Name

English

2-PROPENOIC ACID, 3-(3,4-DIHYDROXYPHENYL)-

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C68539