DIM-C-pPhOH (also known as C-DIM8) is a Nur77 (NR4A1) antagonist. In a metastasis model, DIM-C-pPhOH prevents the growth of lung cancer cells and tumors. When pancreatic and colon cancer cells are treated with C-DIM8, it mimics the effects of NR4A1 knockdown and lowers the expression of β1-integrin, as well as β1-integrin-regulated genes and responses, such as migration and adhesion. A member of the nuclear receptor family of transcription factors' nerve growth factor-I-B subfamily, Nur77 is an orphan receptor. The findings show a fresh approach for β1-integrin targeting in pancreatic and colon cancer cells and suggest potential clinical uses for C-DIM/NR4A1 antagonists in the treatment of colon and pancreatic cancer.

Physicochemical Properties

Molecular Formula	C23H18N2O
Molecular Weight	338.41
Exact Mass	338.141
Elemental Analysis	C, 81.63; H, 5.36; N, 8.28; O, 4.73
CAS #	151358-47-3
Related CAS #	151358-47-3
PubChem CID	2940609
Appearance	Off-white to pink solid powder
Density	1.3±0.1 g/cm3
Boiling Point	610.2±50.0 °C at 760 mmHg
Flash Point	322.9±30.1 °C
Vapour Pressure	0.0±1.8 mmHg at 25°C
Index of Refraction	1.770
LogP	4.8
Hydrogen Bond Donor Count	3
Hydrogen Bond Acceptor Count	1
Rotatable Bond Count	3
Heavy Atom Count	26
Complexity	443
Defined Atom Stereocenter Count	0
SMILES	O([H])C1C([H])=C([H])C(=C([H])C=1[H])C([H])(C1=C([H])N([H])C2=C([H])C([H])=C([H])C([H])=C12)C1=C([H])N([H])C2=C([H])C([H])=C([H])C([H])=C12
InChi Key	QCPDFNWJBQMXLI-UHFFFAOYSA-N
InChi Code	InChI=1S/C23H18N2O/c26-16-11-9-15(10-12-16)23(19-13-24-21-7-3-1-5-17(19)21)20-14-25-22-8-4-2-6-18(20)22/h1-14,23-26H
Chemical Name	4-[bis(1H-indol-3-yl)methyl]phenol
Synonyms	DIM-C pPhOH; DIM-C pPhOH; DIM C-pPhOH; C-DIM8; C DIM8; C-DIM 8
HS Tariff Code	2934.99.9001
Storage	Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Shipping Condition	Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Biological Activity

Targets	Nur77 (IC50 = 13.0 μM); Nur77 (IC50 = 13.6 μM)
ln Vitro	DIM-C-pPhOH (7.5-20 μM; 24 hours; ACHN and 786-O cells) treatment significantly decreases cell proliferation[1]. DIM-C-pPhOH (20 μM; 24 hours; ACHN and 786-O cells) treatment results in Annexin V staining in ACHN and 786-O cells, confirming that DIM-C-pPhOH induces apoptosis and also induces caspase 7 and 8 cleavage[1]. DIM-C-pPhOH (15-20 μM; 24 hours; ACHN and 786-O cells) treatment inhibits NR4A1-regulated expression of survivin, bcl-2 and EGFR in ACHN and 786-O cells. Additionally, it activates AMPK, stimulates sestrin 2, and inhibits the activation of mTOR and downstream kinases[1]. DIM-C-pPhOH reduces expression of β1-integrin protein and mRNA as well as β1-integrin-dependent responses in MCF7, MDA-MB-231, and SKBR3. The latter two cell lines are also prevented from migrating[2].
ln Vivo	DIM-C-pPhOH (30 mg/kg; oral gavage; daily; for 50 days; male athymic nude mice) treatment results in a significant inhibition of tumor growth[1].
References	[1]. Nuclear Receptor 4A1 (NR4A1) as a Drug Target for Renal Cell Adenocarcinoma. PLoS One. 2015 Jun 2;10(6):e0128308. [2]. NR4A1 Antagonists Inhibit β1-Integrin-Dependent Breast Cancer Cell Migration. Mol Cell Biol. 2016 Apr 15;36(9):1383-94.

Solubility Data

Solubility (In Vitro)

DMSO: 68~125 mg/mL(201.0~369.4 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.08 mg/mL (6.15 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.08 mg/mL (6.15 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 3: ≥ 2.08 mg/mL (6.15 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.9550 mL	14.7750 mL	29.5500 mL
	5 mM	0.5910 mL	2.9550 mL	5.9100 mL
	10 mM	0.2955 mL	1.4775 mL	2.9550 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.