Nemadipine-A is a specific inhibitor of the EGL-19 Ca2+ channel. Nemadipine-A is a cell-permeable (penetrable) L-type calcium channel inhibitor that sensitizes TRAIL-resistant cancer cells to this ligand.

Physicochemical Properties

Molecular Formula	C19H18F5NO4
Molecular Weight	419.34
Exact Mass	419.116
CAS #	54280-71-6
PubChem CID	2856102
Appearance	White to light yellow solid powder
LogP	4.071
Hydrogen Bond Donor Count	1
Hydrogen Bond Acceptor Count	10
Rotatable Bond Count	7
Heavy Atom Count	29
Complexity	669
Defined Atom Stereocenter Count	0
SMILES	CCOC(=O)C1=C(NC(=C(C1C2=C(C(=C(C(=C2F)F)F)F)F)C(=O)OCC)C)C
InChi Key	QABNLWXKUCMDBP-UHFFFAOYSA-N
InChi Code	InChI=1S/C19H18F5NO4/c1-5-28-18(26)9-7(3)25-8(4)10(19(27)29-6-2)11(9)12-13(20)15(22)17(24)16(23)14(12)21/h11,25H,5-6H2,1-4H3
Chemical Name	diethyl 2,6-dimethyl-4-(2,3,4,5,6-pentafluorophenyl)-1,4-dihydropyridine-3,5-dicarboxylate
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

ln Vitro	Nemadipine-A is an extremely potent and selective EGL-19 inhibitor. The elevated level of paralysis shown in egl-19(ad695); crIs4 mutants can be eliminated with nemadipine-A (µM)[1]. Nemadipine-A downregulates the anti-apoptotic protein survivin, which potentiates TRAIL-induced apoptosis in TRAIL-resistant lung cancer cells[2]. H1299 lung cancer cells are made more susceptible to TRAIL-induced cytotoxicity by nemadipine-A[2]. When TRAIL (20 ng/mL) and nemadipine-A (20 μM) are combined, caspase-mediated apoptotic cell death is induced[2].
Cell Assay	Cell Viability Assay[2] Cell Types: H1299 lung adenocarcinoma cells Tested Concentrations: 0, 5, 10, 20, and 30 μM Incubation Duration: 8 hrs (hours) Experimental Results: H1299 cells were resistant to the apoptotic effects of TRAIL, but the co-administration of Nemadipine-A and TRAIL in these cells resulted in notably increased cytotoxicity in a dose-dependent manner. Western Blot Analysis[2] Cell Types: H1299 cells Tested Concentrations: 20 μM Incubation Duration: 8 hrs (hours) Experimental Results: Co-treated with TRAIL and Nemadipine-A (T/N; 20 ng/mL and 20 μM respectively) induced cell death in H1299 cells.
References	[1]. The atypical calpains: evolutionary analyses and roles in Caenorhabditis elegans cellular. PLoS Genet. 2012;8(3):e1002602.degeneration. [2]. Down-Regulation of Survivin by Nemadipine-A Sensitizes Cancer Cells to TRAIL-Induced Apoptosis. Biomol Ther (Seoul). 2013 Jan;21(1):29-34.
Additional Infomation	Nemadipine-A is a dihydropyridine that is that is 1,4-dihydropyridine which is substituted at positions 2 and 6 by methyl groups, at positions 3 and 5 by ethoxycarbonyl groups, and at position 4 by a pentafluorophenyl group. An L-type calcium channel alpha1-subunit antagonist. When exposed to the microscopic soil nematode Caenorhabditis elegans, nemadipine-A induces a variety of defects including those affecting morphology and egg laying. It has a role as a calcium channel blocker. It is a dihydropyridine, a diester, a member of pentafluorobenzenes, an ethyl ester and a member of dicarboxylic acids and O-substituted derivatives.

Solubility Data

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	2.3847 mL	11.9235 mL	23.8470 mL
	5 mM	0.4769 mL	2.3847 mL	4.7694 mL
	10 mM	0.2385 mL	1.1923 mL	2.3847 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.