Details
Stereochemistry | ACHIRAL |
Molecular Formula | C17H14N2 |
Molecular Weight | 246.3065 |
Optical Activity | NONE |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
C(C1=CNC2=CC=CC=C12)C3=CNC4=C3C=CC=C4
InChI
InChIKey=VFTRKSBEFQDZKX-UHFFFAOYSA-N
InChI=1S/C17H14N2/c1-3-7-16-14(5-1)12(10-18-16)9-13-11-19-17-8-4-2-6-15(13)17/h1-8,10-11,18-19H,9H2
3,3′-diindolylmethane or diindolylmethane (DIM), a natural product from cruciferous vegetables, which possesses chemopreventive activity in all stages of breast cancer carcinogenesis and is under investigation for the different form of cancer. DIM selectively induced proteasome-mediated degradation of the class I histone deacetylases (HDAC1, HDAC2, HDAC3, and HDAC8) without affecting the class II HDAC proteins (HDAC4, 5, 6, 7, and 10). Histone deacetylases are components of high molecular weight multisubunit complexes of co-repressor proteins that are recruited by transcription factors to the promoters to regulate gene expression. In addition, was identified another mechanism of action: DIM suppressed cancer cells proliferation and miR-30e down-regulated during this effect. miR-30e targeted the 3'-UTR of ATG5 to inhibit its translation. Thus DIM may through the miR-30e-ATG5 modulating autophagy inhibit the proliferation of gastric cancer cells. DIM is also sold as absorption-enhanced formulation under the brand name Patented BioResponse DIM®. BioResponse DIM supports a more favorable metabolism of estrogen and supports the production of 2 hydroxyestrone and 2-methoxyestrone, key metabolites in men and women. DIM is used to treat recurrent respiratory papillomatosis and it has been studied for patients with cervical intraepithelial neoplasia.
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
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Target ID: Q13547 Gene ID: 3065.0 Gene Symbol: HDAC1 Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/20068155 |
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Target ID: Q92769 Gene ID: 3066.0 Gene Symbol: HDAC2 Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/20068155 |
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Target ID: Q9BY41|||Q86VC8 Gene ID: 55869.0 Gene Symbol: HDAC8 Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/20068155 |
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Target ID: O15379 Gene ID: 8841.0 Gene Symbol: HDAC3 Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/20068155 |
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Target ID: 407034.0 Gene Symbol: MIR30E Sources: https://www.ncbi.nlm.nih.gov/pubmed/27372603 |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
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Preventing | Unknown Approved UseUnknown |
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Primary | Unknown Approved UseUnknown |
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Primary | Unknown Approved UseUnknown |
Cmax
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
42 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20733950 |
75 mg single, oral dose: 75 mg route of administration: Oral experiment type: SINGLE co-administered: |
3,3'-DIINDOLYLMETHANE plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: MALE food status: UNKNOWN |
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79 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/18843002 |
150 mg single, oral dose: 150 mg route of administration: Oral experiment type: SINGLE co-administered: |
3,3'-DIINDOLYLMETHANE plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
|
104 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20733950 |
150 mg single, oral dose: 150 mg route of administration: Oral experiment type: SINGLE co-administered: |
3,3'-DIINDOLYLMETHANE plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: MALE food status: UNKNOWN |
|
108 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/18843002 |
300 mg single, oral dose: 300 mg route of administration: Oral experiment type: SINGLE co-administered: |
3,3'-DIINDOLYLMETHANE plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
|
134 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20733950 |
225 mg single, oral dose: 225 mg route of administration: Oral experiment type: SINGLE co-administered: |
3,3'-DIINDOLYLMETHANE plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: MALE food status: UNKNOWN |
|
236 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20733950 |
300 mg single, oral dose: 300 mg route of administration: Oral experiment type: SINGLE co-administered: |
3,3'-DIINDOLYLMETHANE plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: MALE food status: UNKNOWN |
AUC
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
192 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20733950 |
75 mg single, oral dose: 75 mg route of administration: Oral experiment type: SINGLE co-administered: |
3,3'-DIINDOLYLMETHANE plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: MALE food status: UNKNOWN |
|
314 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/18843002 |
150 mg single, oral dose: 150 mg route of administration: Oral experiment type: SINGLE co-administered: |
3,3'-DIINDOLYLMETHANE plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
|
450 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20733950 |
150 mg single, oral dose: 150 mg route of administration: Oral experiment type: SINGLE co-administered: |
3,3'-DIINDOLYLMETHANE plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: MALE food status: UNKNOWN |
|
532 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/18843002 |
300 mg single, oral dose: 300 mg route of administration: Oral experiment type: SINGLE co-administered: |
3,3'-DIINDOLYLMETHANE plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
|
599 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20733950 |
225 mg single, oral dose: 225 mg route of administration: Oral experiment type: SINGLE co-administered: |
3,3'-DIINDOLYLMETHANE plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: MALE food status: UNKNOWN |
|
899 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20733950 |
300 mg single, oral dose: 300 mg route of administration: Oral experiment type: SINGLE co-administered: |
3,3'-DIINDOLYLMETHANE plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: MALE food status: UNKNOWN |
T1/2
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
3 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/18843002 |
150 mg single, oral dose: 150 mg route of administration: Oral experiment type: SINGLE co-administered: |
3,3'-DIINDOLYLMETHANE plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
|
4.5 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/18843002 |
300 mg single, oral dose: 300 mg route of administration: Oral experiment type: SINGLE co-administered: |
3,3'-DIINDOLYLMETHANE plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
PubMed
Title | Date | PubMed |
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Dietary indoles and isothiocyanates that are generated from cruciferous vegetables can both stimulate apoptosis and confer protection against DNA damage in human colon cell lines. | 2001 Aug 15 |
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3,3'-diindolylmethane, a major condensation product of indole-3-carbinol, is a potent estrogen in the rainbow trout. | 2001 Feb 1 |
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Methyl-substituted diindolylmethanes as inhibitors of estrogen-induced growth of T47D cells and mammary tumors in rats. | 2001 Mar |
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Cytostatic effects of 3,3'-diindolylmethane in human endometrial cancer cells result from an estrogen receptor-mediated increase in transforming growth factor-alpha expression. | 2001 Nov |
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Effects of treatment of rats with indole-3-carbinol on apoptosis in the mammary gland and mammary adenocarcinomas. | 2003 May-Jun |
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Pharmacokinetics and tissue disposition of indole-3-carbinol and its acid condensation products after oral administration to mice. | 2004 Aug 1 |
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Potent ligand-independent estrogen receptor activation by 3,3'-diindolylmethane is mediated by cross talk between the protein kinase A and mitogen-activated protein kinase signaling pathways. | 2004 Feb |
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Physiological modeling of formulated and crystalline 3,3'-diindolylmethane pharmacokinetics following oral administration in mice. | 2004 Jun |
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A new class of peroxisome proliferator-activated receptor gamma (PPARgamma) agonists that inhibit growth of breast cancer cells: 1,1-Bis(3'-indolyl)-1-(p-substituted phenyl)methanes. | 2004 Mar |
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Lack of antagonism of 2,3,7,8-tetrachlorodibenzo-p-dioxin's (TCDDs) induction of cytochrome P4501A1 (CYP1A1) by the putative selective aryl hydrocarbon receptor modulator 6-alkyl-1,3,8-trichlorodibenzofuran (6-MCDF) in the mouse hepatoma cell line Hepa-1c1c7. | 2004 Nov 20 |
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Multifocal angiostatic therapy: an update. | 2005 Dec |
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Indole-3-carbinol (I3C) inhibits cyclin-dependent kinase-2 function in human breast cancer cells by regulating the size distribution, associated cyclin E forms, and subcellular localization of the CDK2 protein complex. | 2005 Mar 11 |
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Gateways to clinical trials. | 2005 Oct |
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Molecular targets of dietary polyphenols with anti-inflammatory properties. | 2005 Oct 31 |
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3,3'-diindolylmethane (DIM) and its derivatives induce apoptosis in pancreatic cancer cells through endoplasmic reticulum stress-dependent upregulation of DR5. | 2006 Apr |
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Synthetic dimer of indole-3-carbinol: second generation diet derived anti-cancer agent in hormone sensitive prostate cancer. | 2006 Apr 1 |
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Single-dose and multiple-dose administration of indole-3-carbinol to women: pharmacokinetics based on 3,3'-diindolylmethane. | 2006 Dec |
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Oxidized bis(indolyl)methane: a simple and efficient chromogenic-sensing molecule based on the proton transfer signaling mode. | 2006 Jan 19 |
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Multiple, disparate roles for calcium signaling in apoptosis of human prostate and cervical cancer cells exposed to diindolylmethane. | 2006 Mar |
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Fate of 3,3'-diindolylmethane in cultured MCF-7 human breast cancer cells. | 2006 Mar |
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Using salmonid microarrays to understand the dietary modulation of carcinogenesis in rainbow trout. | 2006 Mar |
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Inhibition of breast cancer cell growth and induction of cell death by 1,1-bis(3'-indolyl)methane (DIM) and 5,5'-dibromoDIM. | 2006 May 18 |
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Fas-mediated apoptosis in cholangiocarcinoma cells is enhanced by 3,3'-diindolylmethane through inhibition of AKT signaling and FLICE-like inhibitory protein. | 2006 Nov |
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Estrogen receptor alpha as a target for indole-3-carbinol. | 2006 Oct |
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Extended treatment with physiologic concentrations of dietary phytochemicals results in altered gene expression, reduced growth, and apoptosis of cancer cells. | 2007 Nov |
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Curcumin enhances the apoptosis-inducing potential of TRAIL in prostate cancer cells: molecular mechanisms of apoptosis, migration and angiogenesis. | 2007 Oct 4 |
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1,1-bis(3'-indolyl)-1-(p-methoxyphenyl)methane activates Nur77-independent proapoptotic responses in colon cancer cells. | 2008 Apr |
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Red clover isoflavones biochanin A and formononetin are potent ligands of the human aryl hydrocarbon receptor. | 2008 Jan |
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An insight into the mechanism of inhibition of unusual bi-subunit topoisomerase I from Leishmania donovani by 3,3'-di-indolylmethane, a novel DNA topoisomerase I poison with a strong binding affinity to the enzyme. | 2008 Jan 15 |
Patents
Sample Use Guides
75 mg of 3,3´-diindolylmethane (DIM) once a day for 30 days. Two pills of BioResponse DIM® 150 are equal to 75 mg of DIM pure.
Route of Administration:
Oral
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/27372603
Curator's Comment: 3,3′-diindolylmethane (DIM) dose-dependently inhibited the growth of gastric cancer cells in vitro. ATG5 and LC3 were activated by DIM in gastric cancer cells. Furthermore, miR-30e was down-regulated by DIM and miR-30e targeted the 3'-UTR of ATG5 to inhibit its translation.
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NCI_THESAURUS |
C54630
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C54677
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DSLD |
1346 (Number of products:303)
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DTXSID8037047
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3,3'-Diindolylmethane
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DB11875
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1603521
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C53434
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C016392
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3071
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100000126223
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SUB32854
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ACTIVE MOIETY