C-DIM12 is a novel, pphytochemical-based Nurr1 activator with neuroprotective properties. In bladder cancer cells and tumors, it activates the Nurr1-mediated apoptosis axis while suppressing NF-B-dependent gene expression in glial cells. In primary neurons and cell lines, C-DIM12 increases Nurr1 and DA gene expression. In vitro, C-DIM12 increases the expression of dopaminergic genes and guards against 6-hydroxydopamine neurotoxicity. In the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model of PD in mice, C-DIM12 activates Nurr1 in cancer cells and prevents the loss of dopaminergic neurons. C-DIM12 improved neuronal survival after exposure to 6-OHDA and increased expression of transfected human Nurr1 and Nurr1 protein in primary dopaminergic neurons. These findings suggest that C-DIM12 promotes the expression of Nurr1-regulated genes that are neuroprotective in DA neurons.

Physicochemical Properties

Molecular Formula	C23H17CLN2
Molecular Weight	356.85
Exact Mass	356.108
Elemental Analysis	C, 77.41; H, 4.80; Cl, 9.93; N, 7.85
CAS #	178946-89-9
Related CAS #	178946-89-9
PubChem CID	5302583
Appearance	Light Brown solid powder
Density	1.3±0.1 g/cm3
Boiling Point	585.6±45.0 °C at 760 mmHg
Flash Point	336.1±14.3 °C
Vapour Pressure	0.0±1.6 mmHg at 25°C
Index of Refraction	1.747
LogP	6.13
Hydrogen Bond Donor Count	2
Hydrogen Bond Acceptor Count	0
Rotatable Bond Count	3
Heavy Atom Count	26
Complexity	443
Defined Atom Stereocenter Count	0
SMILES	ClC1C=CC(C(C2=CNC3=CC=CC=C23)C2=CNC3=CC=CC=C23)=CC=1
InChi Key	FIDOCHXHMJHKRW-VHQVDBNASA-N
InChi Code	InChI=1S/C33H45NO10/c1-17(35)44-33-21-19(14-31(38,28(42-6)26(33)36)27(21)43-29(37)18-10-8-7-9-11-18)32-20(40-4)12-13-30(16-39-3)15-34(2)25(32)22(33)23(41-5)24(30)32/h7-11,19-28,36,38H,12-16H2,1-6H3/t19-,20+,21-,22+,23+,24-,25?,26+,27-,28+,30+,31-,32+,33-/m1/s1
Chemical Name	[(1S,2R,3R,4R,5R,6S,7S,8R,9R,13S,16S,17R,18R)-8-acetyloxy-5,7-dihydroxy-6,16,18-trimethoxy-13-(methoxymethyl)-11-methyl-11-azahexacyclo[7.7.2.12,5.01,10.03,8.013,17]nonadecan-4-yl] benzoate
Synonyms	C-DIM12; C-DIM 12; C-DIM-12
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 Note: This product requires protection from light (avoid light exposure) during transportation and storage.
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	Nurr1
ln Vitro	C-DIM12 induces Nurr1 and DA gene expression in cell lines and primary neurons[3]. In vitro, C-DIM12 inhibits astrocyte inflammatory signaling. Nitric oxide synthase (NOS2), interleukin-6 (IL-6), and chemokine (C-C motif) ligand 2 (CCL2) are NF-B-regulated genes that are inhibited by lipopolysaccharide (LPS) in BV-2 microglia. Nurr1-RNA interference attenuated these effects. Additionally, C-DIM12 increased nuclear translocation of Nurr1 primary microglia while decreasing NF-B activation in NF-B-GFP reporter cells. C-DIM12 increases Nurr1 binding to the p65-binding site while decreasing lipopolysaccharide-induced p65 binding to the NOS2 promoter. Additionally, CoREST (Corepressor for Repressor Element 1 Silencing Transcription Factor) and NCOR2 (Nuclear Receptor Corepressor 2) binding was stabilized by C-DIM12[2].
ln Vivo	C-DIM12 has the neuroprotective activity in MPTPp-treated mice[2].
Cell Assay	For up to 24 hours, NF-B-GFP HEK cells are exposed to 30 ng/ml of TNF in the presence of 100 μM C-DIM12. C-DIM12 effectively inhibits NF-B-GFP expression in the NF-B-GFP HEK cells after TNF treatment, showing a statistically significant decrease in total GFP fluorescence per cell.
Animal Protocol	Transgenic NF-κB/EGFP reporter mice (C57Bl/6 background) 50 mg/kg oral administration IV, Oral gavage
References	[1] Toxicol Sci . 2015 Feb;143(2):360-73. [2] Mol Pharmacol . 2015 Jun;87(6):1021-34. [3] Neurosci Lett . 2015 Oct 21;607:83-89.

Solubility Data

Solubility (In Vitro)

DMSO: ~71 mg/mL (~199.0 mM) Water: <1 mg/mL Ethanol: ~71 mg/mL (~199.0 mM)

Solubility (In Vivo)

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples. Injection Formulations (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] *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. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Oral Formulations Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.8023 mL	14.0115 mL	28.0230 mL
	5 mM	0.5605 mL	2.8023 mL	5.6046 mL
	10 mM	0.2802 mL	1.4011 mL	2.8023 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.