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BAYK 8644 [(+/-)-Bay K-8644] is a novel and potent L-type Ca2+ channel activator with an EC50 of 17.3 nM. (+/-)-Bay K 8644, a conventional racemic mixture of Bay K 8644, is widely used as an L-type Ca(2+) channel agonist.
Physicochemical Properties
| Molecular Formula | C16H15N2O4F3 |
| Molecular Weight | 356.2965 |
| Exact Mass | 356.098 |
| CAS # | 71145-03-4 |
| Related CAS # | (S)-(-)-Bay-K-8644;98625-26-4;(R)-(+)-Bay-K-8644;98791-67-4 |
| PubChem CID | 2303 |
| Appearance | Light yellow to yellow solid powder |
| Density | 1.37g/cm3 |
| Boiling Point | 404.3ºC at 760 mmHg |
| Flash Point | 198.3ºC |
| Index of Refraction | 1.545 |
| LogP | 4.199 |
| Hydrogen Bond Donor Count | 1 |
| Hydrogen Bond Acceptor Count | 8 |
| Rotatable Bond Count | 3 |
| Heavy Atom Count | 25 |
| Complexity | 634 |
| Defined Atom Stereocenter Count | 0 |
| InChi Key | ZFLWDHHVRRZMEI-UHFFFAOYSA-N |
| InChi Code | InChI=1S/C16H15F3N2O4/c1-8-12(15(22)25-3)13(14(21(23)24)9(2)20-8)10-6-4-5-7-11(10)16(17,18)19/h4-7,13,20H,1-3H3 |
| Chemical Name | methyl 2,6-dimethyl-5-nitro-4-[2-(trifluoromethyl)phenyl]-1,4-dihydropyridine-3-carboxylate |
| Synonyms | (+/-)-Bay K-8644; BAYK 8644; (+/-)-Bay-K-8644; BAYK8644; (+/-)-Bay K 8644; BAYK-8644. |
| 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 | When Bay K 8644 (1 μM) was applied to 2-day-old newborn rat ventricular cardiomyocytes, the cells' L-type calcium current density increased. A greater rise in the L-type calcium current density of Bay K 8644 in 2-day-cultured cells compared to 7-day-cultured cells can be attributed to variations in the phosphorylation levels of calcium channels at each developmental stage [4]. |
| ln Vitro |
When Bay K 8644 (1 μM) was applied to 2-day-old newborn rat ventricular cardiomyocytes, the cells' L-type calcium current density increased. A greater rise in the L-type calcium current density of Bay K 8644 in 2-day-cultured cells compared to 7-day-cultured cells can be attributed to variations in the phosphorylation levels of calcium channels at each developmental stage [4]. BAY K 8644 (1 μM) alone increased the peak L-type calcium channel current (\(I_{Ca(peak)}\)) to 293.0 ± 107.9% of control in guinea-pig ventricular myocytes. [1] In the presence of 30 μM fendiline, 1 μM BAY K 8644 further reduced \(I_{Ca(peak)}\) to 1.0 ± 1.6% of control, instead of stimulating it, indicating a paradoxical inhibitory effect. [1] The pure agonist enantiomer (4S)-BAY K 8644 (1 μM) also caused further inhibition of \(I_{Ca(peak)}\) to 4.7 ± 1.1% of control in the presence of fendiline. [1] In contrast, in the presence of other calcium channel blockers (nifedipine, verapamil, diltiazem), 1 μM BAY K 8644 produced the expected agonist effect and increased \(I_{Ca(peak)}\). [1] |
| ln Vivo | In endotoxin-treated hypotensive rats, a single dose of Bay K 8644 as little as 10 μg/kg dramatically raised mean arterial pressure (MAP), but had no impact on normal rats. Additionally, endotoxin-treated rats' heart rates decreased by 37% and control rats' heart rates decreased by 39% in response to Bay K 8644 [5]. |
| Cell Assay |
The whole-cell patch-clamp technique was used to record L-type calcium channel currents (\(I_{Ca}\)) from isolated guinea-pig ventricular myocytes. Cells were superfused with choline-based physiological salt solution and intracellular pipette solution containing CsCl, EGTA, MgCl₂, CaCl₂, HEPES, and K-ATP. Voltage pulses were applied from a holding potential of -90 mV, with a prepulse to -40 mV for 100 ms, followed by a test pulse to +10 mV for 250 ms at 5 s intervals. Currents were low-pass filtered and digitized for analysis. [1] Steady-state inactivation (\(f_{\infty}\)) was determined using a double-pulse protocol: conditioning prepulses from -80 mV to +10 mV (20 s) followed by a test pulse to +10 mV. \(I_{Ca(peak)}\) values were plotted against prepulse potential and fitted to a Boltzmann equation to calculate \(f_{\infty}\). [1] Time constants of activation and inactivation were obtained by fitting single exponential functions to the rising and decaying phases of \(I_{Ca}\) traces elicited by step depolarizations from -10 to +30 mV. [1] |
| References |
[1]. Kinetic modulation of guinea-pig cardiac L-type calcium channels by fendiline and reversal of the effects of Bay K 8644. Br J Pharmacol. 1992 May;106(1):151-6. [2]. Interactions of calcium antagonists and the calcium channel agonist Bay K 8644 on neurotransmission of the mouse isolated vas deferens. Br J Pharmacol. 1989 Feb;96(2):333-40. [3]. Bay K 8644 increases resting Ca2+ spark frequency in ferret ventricular myocytes independent of Ca influx: contrast with caffeine and ryanodine effects. Circ Res. 1998 Dec 14-28;83(12):1192-204. [4]. Effects of Bay K 8644 on L-type calcium current from newborn rat cardiomyocytes in primary culture. J Mol Cell Cardiol. 1996 Oct;28(10):2217-29. [5]. BAY k 8644, a calcium channel agonist, reverses hypotension in endotoxin-shocked rats. Eur J Pharmacol. 1986 Nov 4;130(3):169-75. |
| Additional Infomation |
Methyl 2,6-dimethyl-5-nitro-4-[2-(trifluoromethyl)phenyl]-1,4-dihydropyridine-3-carboxylate is a pentasubstituted dihydropyridine carrying methoxycarbonyl, 2-(trifluoromethyl)phenyl and nitro substituents at positions 3, 4 and 5 respectively as well as two methyl substituents at positions 2 and 6. It is a dihydropyridine, a methyl ester, a C-nitro compound and a member of (trifluoromethyl)benzenes. A dihydropyridine derivative, which, in contrast to NIFEDIPINE, functions as a calcium channel agonist. The compound facilitates Ca2+ influx through partially activated voltage-dependent Ca2+ channels, thereby causing vasoconstrictor and positive inotropic effects. It is used primarily as a research tool. BAY K 8644 is a racemic mixture of (4S)-Bay K 8644 (agonist) and (4R)-Bay K 8644 (antagonist). [1] The paradoxical inhibition of \(I_{Ca}\) by BAY K 8644 in the presence of fendiline is proposed to result from an allosteric interaction between fendiline and the dihydropyridine agonist site on the L-type calcium channel. [1] The study suggests that diphenylalkylamines like fendiline may act at a site distinct from classical calcium channel blockers. [1] |
Solubility Data
| Solubility (In Vitro) | DMSO : ~83.33 mg/mL (~233.88 mM) |
| Solubility (In Vivo) |
Solubility in Formulation 1: 2.08 mg/mL (5.84 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication. 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 2: ≥ 1.67 mg/mL (4.69 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 16.7 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.8066 mL | 14.0331 mL | 28.0662 mL | |
| 5 mM | 0.5613 mL | 2.8066 mL | 5.6132 mL | |
| 10 mM | 0.2807 mL | 1.4033 mL | 2.8066 mL |