-(+)-Bay-K-8644 Chemical Structure.png)
(R)-(+)-Bay-K-8644, the R-isomer of Bay-K-8644, is a novel and potent a calcium channel inhibitor/blocker that inhibits Ba2+ currents (IBa) (IC50=975 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 # | 98791-67-4 |
| Related CAS # | Bay K 8644;71145-03-4;(S)-(-)-Bay-K-8644;98625-26-4 |
| PubChem CID | 6604881 |
| Appearance | Light yellow to yellow solid powder |
| Density | 1.4±0.1 g/cm3 |
| Boiling Point | 429.2±45.0 °C at 760 mmHg |
| Flash Point | 213.4±28.7 °C |
| Vapour Pressure | 0.0±1.0 mmHg at 25°C |
| Index of Refraction | 1.543 |
| LogP | 2.39 |
| Hydrogen Bond Donor Count | 1 |
| Hydrogen Bond Acceptor Count | 8 |
| Rotatable Bond Count | 3 |
| Heavy Atom Count | 25 |
| Complexity | 634 |
| Defined Atom Stereocenter Count | 1 |
| SMILES | CC1=C([C@H](C(=C(N1)C)[N+](=O)[O-])C2=CC=CC=C2C(F)(F)F)C(=O)OC |
| 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; Bay-K 8644 (R)-(-)-; (R)-(-)-Bay-K-8644; Bay-K-8644 (S)-(-)-; (R)-(-)-Bay K-8644; (-)-BAY-R-5417; (-)-BAY-K-8644; (-)-BAY R-5417; BAYK 8644; BAYK8644; 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 | (R)-(+)-Bay-K-8644 is a conventional racemic combination that is frequently employed as an L-type Ca2+ channel agonist (Bay K 8644). With (R)-(+)-Bay-K-8644 functioning as an antagonist and S(-)-Bay K 8644 working as an agonist, each optical isomer has opposing effects on IBa. Ba2+ current (IBa) is inhibited by (R)-(+)-Bay-K-8644 (IC50=975 nM). Applying (R)-(+)-Bay-K-8644 (0.5 μM) suppressed IBa to 71±10% of control. when (R)-(+)-Bay-K-8644IBa is present[1]. An inhibitor of calcium channels is (R)-(+)-Bay-K-8644 [2]. |
| ln Vitro |
(R)-(+)-Bay-K-8644 is a conventional racemic combination that is frequently employed as an L-type Ca2+ channel agonist (Bay K 8644). With (R)-(+)-Bay-K-8644 functioning as an antagonist and S(-)-Bay K 8644 working as an agonist, each optical isomer has opposing effects on IBa. Ba2+ current (IBa) is inhibited by (R)-(+)-Bay-K-8644 (IC50=975 nM). Applying (R)-(+)-Bay-K-8644 (0.5 μM) suppressed IBa to 71±10% of control. when (R)-(+)-Bay-K-8644IBa is present[1]. An inhibitor of calcium channels is (R)-(+)-Bay-K-8644 [2]. In intact mouse urinary bladder smooth muscle (UBSM) strips, application of (R)-(+)-Bay-K-8644 (1 µM) significantly reduced the frequency of Ca²⁺ sparklets (small, discrete membrane-localized Ca²⁺ elevations) from 0.20 ± 0.08 Hz/mm² to 0.034 ± 0.021 Hz/mm². [1] The amplitude of the remaining Ca²⁺ sparklets in the presence of (R)-(+)-Bay-K-8644 (1 µM) was not significantly different from control (0.08 ± 0.004 F/F₀ vs. control 0.08 ± 0.002 F/F₀). [1] When UBSM strips were exposed to both the sarcoplasmic reticulum Ca²⁺-ATPase inhibitor cyclopiazonic acid (CPA, 10 µM) and (R)-(+)-Bay-K-8644 (1 µM), a significant decrease in Ca²⁺ sparklet frequency was also observed (0.15 ± 0.03 Hz/mm² vs. control 0.34 ± 0.08 Hz/mm²), and the sparklet amplitude remained unaffected. This indicates that CPA-induced sparklet activity is also dependent on VGCCs. [1] |
| Cell Assay |
The study utilized intact smooth muscle strips from the urinary bladder of male C57BL/6 mice (6-10 weeks old). Strips were loaded with the fluorescent Ca²⁺ indicator Oregon Green BAPTA-1 AM (10 µM) for 70 minutes at 35°C. [1] Ca²⁺ sparklets were imaged using Total Internal Reflection Fluorescence (TIRF) microscopy. The strip was placed serosal side down on a coverslip, perfused with oxygenated Krebs solution at 25°C, and gently weighted to position cells within the evanescent field. Images were captured at 150 Hz. [1] For drug application, (R)-(+)-Bay-K-8644 (1 µM) was dissolved in DMSO as a stock solution and diluted in Krebs solution on the day of use. A minimum exposure period of 15 minutes was allowed before imaging. Ca²⁺ sparklets were detected and analyzed using automated (LC Pro plugin for ImageJ) and manual methods, with criteria including a minimum duration of 3 frames, a signal 2.5 standard deviations above baseline, and a peak amplitude of at least 0.05 F/F₀. Frequency was normalized to cell membrane area within the TIRF zone. [1] |
| References |
[1]. Antagonistic actions of S(-)-Bay K 8644 on cyclic nucleotide-induced inhibition of voltage-dependent Ba(2+) currents in guinea pig gastric antrum. Naunyn Schmiedebergs Arch Pharmacol. 2008 Dec;378(6):609-15. [2]. L-type Ca2+ channel sparklets revealed by TIRF microscopy in mouse urinary bladder smooth muscle. PLoS One. 2014 Apr 3;9(4):e93803. |
| Additional Infomation |
(R)-Bay-K-8644 is a methyl 2,6-dimethyl-5-nitro-4-[2-(trifluoromethyl)phenyl]-1,4-dihydropyridine-3-carboxylate in which the 4-position has (R)-configuration. It is an enantiomer of a (S)-Bay-K-8644. 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. (R)-(+)-Bay-K-8644 was used as a pharmacological tool to inhibit L-type VGCCs and study their role in generating Ca²⁺ sparklets in bladder smooth muscle. [1] The study suggests that Ca²⁺ sparklets, which are inhibited by (R)-(+)-Bay-K-8644, represent a form of store-operated calcium entry (SOCE) that can occur through VGCC complexes in excitable cells, particularly after pharmacological store depletion with CPA. [1] The enantiomer (R)-(+)-Bay-K-8644 is described here as an inhibitor, in contrast to its enantiomer (S)-(-)-Bay-K-8644, which is typically known as an L-type channel agonist. [1] |
Solubility Data
| Solubility (In Vitro) | DMSO : ≥ 300 mg/mL (~841.99 mM) |
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (7.02 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 (7.02 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 ultrasonication. 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 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. (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 |