Manidipine 2HCl 89226-75-5_CDK_Cell Cycle_Signaling Pathways_Products

Manidipine 2HCl (also called CV-4093; CV4093), the dihydrochloride salt form of Manidipine, is a calcium channel blocker/CCB that is used clinically as an antihypertensive agent. It inhibits the voltage-dependent calcium inward currents in smooth muscle cells, which results in systemic vasodilation. Comparing manidipine to other Ca2+ channel antagonists, it is said to exhibit minimal cardiodepression and selectively block T-type Ca2+ channels while having a high selectivity for the vasculature.

Physicochemical Properties

Molecular Formula

C35H38N4O6.2HCL

Molecular Weight

683.62

Exact Mass

682.2324904

Elemental Analysis

C, 61.49; H, 5.90; Cl, 10.37; N, 8.20; O, 14.04

CAS #

89226-75-5

Related CAS #

Manidipine;89226-50-6

PubChem CID

150762

Appearance

White to off-white solid powder

Boiling Point

722ºC at 760 mmHg

Melting Point

211 °C(dec.)

LogP

6.482

Hydrogen Bond Donor Count

Hydrogen Bond Acceptor Count

Rotatable Bond Count

Heavy Atom Count

Complexity

1090

Defined Atom Stereocenter Count

SMILES

Cl.O=C(C1C(C2C=C([N+](=O)[O-])C=CC=2)C(C(OCCN2CCN(C(C3C=CC=CC=3)C3C=CC=CC=3)CC2)=O)=C(C)NC=1C)OC

InChi Key

JINNGBXKBDUGQT-UHFFFAOYSA-N

InChi Code

InChI=1S/C35H38N4O6.2ClH/c1-24-30(34(40)44-3)32(28-15-10-16-29(23-28)39(42)43)31(25(2)36-24)35(41)45-22-21-37-17-19-38(20-18-37)33(26-11-6-4-7-12-26)27-13-8-5-9-14-27;;/h4-16,23,32-33,36H,17-22H2,1-3H3;2*1H

Chemical Name

5-O-[2-(4-benzhydrylpiperazin-1-yl)ethyl] 3-O-methyl 2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate;dihydrochloride

Synonyms

Manidipine HCl; CV-4093; CV4093; CV 4093

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: Please store this product in a sealed and protected environment, avoid exposure to moisture.

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

CDK7/CycH/MAT1 (IC50 = 0.021 μM); CDK2/Cyc E (IC50 = 0.88 μM); CDK5/p35NCK (IC50 = 3 μM); CDK9/cycT (IC50 = 4.2 μM); CDK1/cycB (IC50 = 8.1 μM); CDK4/Cyc D1 (IC50 = 33 μM); CDK6/cycD1 (IC50 = 47 μM)

ln Vitro

Manidipine reduces the Ca²⁺ current at concentrations above 0.1 nM and eliminates it at 100 nM, with a holding potential of -37 mV. The calcium concentration response curves are inhibited by manidipine in a concentration-dependent manner [1]. Manidipine has a pIC50 of 9.3 nM for the renal artery and 9.1 nM for the coronary artery, respectively. [2] Manidipine reduces the mean arterial pressure response to norepinephrine infusion and partially inhibits sympathetic nerve activity. Moreover, manidipine prevents aldosterone secretion. Urine manidipine raises uric acid and calcium levels. [/3] Furthermore, manidipine effectively modifies gene transcriptions implicated in proinflammatory alterations in mesangial cells at nanomolar concentrations. *[4]

ln Vivo

Manidipine (3 mg/kg and 10 mg/kg, p.o.) reduces systolic blood pressure in the three types of hypertensive rats in a dose-dependent manner. Manidipine reduces blood pressure to normotensive levels at a dose of 10 mg/kg within 1 to 3 hours of administration; the antihypertensive effect lasts for at least 8 hours. [5] The hypotensive effect is significantly enhanced by 10 μg/kg of manidipine. (6) At -60 mV potential, manidipine potently inhibits the Ca inward current. The Ca current elicited by depolarization to 0 mV is consistently inhibited by manidipine. The Ca current induced by the -20 mV depolarizing pulse, however, is enhanced by a low concentration of manidipine (1-3 nM) when the membrane potential is maintained at -80 mV.

Cell Assay

The amount of [3H]thymidine incorporated into the DNA of human MCs and the evaluation of cell proliferation are used to quantify the mitogenic effect. To summarize, a 25-mL cell culture bottle is seeded with 1 × 10⁵ quiescent cells, which are maintained in low serum medium containing 0.1% FCS. The next day, the cells are either incubated with low serum medium (abone) or stimulated with PDGF-BB (10 ng/mL) after being preincubated with manidipine (10 nM) for three hours. Every day, the medium is changed, and on days 1, 3, and 5, the cells are counted.

Animal Protocol

Normotensive male Wistar-Kyoto rats and male stroke-prone SHR
1 mg/kg, 3 mg/kg and 10 mg/kg
Administered via p.o.

References

[1]. Eur J Pharmacol . 1993 Nov 9;249(2):231-3.

[2]. TAm Heart J . 1993 Feb;125(2 Pt 2):571-7.

[3]. Am Heart J . 1993 Feb;125(2 Pt 2):635-41.

[4]. Proc Natl Acad Sci U S A . 1992 May 1;89(9):4071-5

[5]. Jpn J Pharmacol . 1988 Oct;48(2):223-8.

[6]. Jpn J Pharmacol . 1989 Oct;51(2):257-65.

[7]. J Pharmacol Exp Ther . 1987 Nov;243(2):703-10.

Additional Infomation

Manidipine dihydrochloride is a diarylmethane.

Solubility Data

Solubility (In Vitro)

DMSO: ~21 mg/mL (~30.7 mM)

Water: <1 mg/mL

Ethanol: <1 mg/mL

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.5 mg/mL (3.66 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 25.0 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: ≥ 2.5 mg/mL (3.66 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 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

Solubility in Formulation 3: 2% DMSO +30%PEG 300 +ddH2O: 2mg/mL

(Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	1.4628 mL	7.3140 mL	14.6280 mL
	5 mM	0.2926 mL	1.4628 mL	2.9256 mL
	10 mM	0.1463 mL	0.7314 mL	1.4628 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.

PeptideDB

Manidipine 2HCl 89226-75-5

CAS No.: 89226-75-5

Physicochemical Properties

Biological Activity

Solubility Data

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PeptideDB

Manidipine 2HCl 89226-75-5

CAS No.: 89226-75-5

Physicochemical Properties

Biological Activity

Solubility Data

Product Recommendation

Latest release

Hot list