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Purity: ≥98%
(S)-(-)-Bay-K-8644, the S-enantiomer of Bay-K-8644, is a novel and potent Ca2+ channel activator that activates Ba2+ currents (IBa) with an EC50 of 32 nM. (+/-)-Bay K 8644, a conventional racemic mixture of Bay K 8644, is widely used as an L-type Ca(2+) channel agonist. Although interactions between Bay K 8644 and cyclic nucleotide have been described, they have not been properly characterized. We have investigated whether two optical isomers of Bay K 8644 (i.e., R(+)- and S(-)-Bay K 8644) modify cyclic nucleotide (cAMP and cGMP)-induced inhibitory effects on nifedipine-sensitive voltage-dependent Ba(2+) currents (I (Ba)) recorded from guinea pig gastric myocytes. Conventional whole-cell recordings were used to compare the effects of R(+)-Bay K 8644 and S(-)-Bay K 8644 on I (Ba). S(-)-Bay K 8644 enhanced the peak amplitude of I (Ba) evoked by depolarizing pulses to +10 mV from a holding potential of -70 mV in a concentration-dependent manner (EC(50) = 32 nM), while R(+)-Bay K 8644 inhibited I (Ba) (IC(50) = 975 nM). When R(+)-Bay K 8644 (0.5 microM) was applied, I (Ba) was suppressed to 71 +/- 10% of control. In the presence of R(+)-Bay K 8644 (0.5 microM), additional application of forskolin and sodium nitroprusside (SNP) further inhibited I (Ba). Conversely, in the presence of S(-)-Bay K 8644 (0.5 microM), subsequent application of forskolin and SNP did not affect I (Ba). Similarly, in the presence of 0.5 microM S(-)-Bay K 8644, db-cAMP and 8-Br-cGMP had no effect on I (Ba). These results indicate that S(-)-Bay K 8644, but not R(+)-Bay K 8644, can prevent the inhibitory actions of two distinct cyclic nucleotide pathways on I (Ba) in gastric myocytes of the guinea pig antrum.
| Targets |
EC50: 32 nM (IBa)[1]
(±)-Bay K 8644, a racemic combination of Bay K 8644, is commonly employed as an L-type Ca2+ channel agonist. Each optical isomer has the opposite effect on IBa (R(+)-Bay K 8644 as an antagonist and (S)-(-)-Bay-K-8644 as an agonist. (S)-(-)-Bay-K-8644 can suppress the inhibitory activities of two separate cyclic nucleotide pathways on IBa in guinea pig stomach myocytes[1]. The Ca2+ channel activity is boosted by 3-30 μM (S)-(-)-Bay-K-8644, an agonist of L-type Ca2+ channels (2). The interactions of two Ca2+ channel activators, (S)-(-)-Bay-K-8644 and FPL 64176, are investigated on smooth muscle L-type Ca2+ channels. FPL 64176 (300 nM) produces persistent contractions in rat tail artery strips. The contractile response is approximately 70% reduced by (S)-(-)-Bay-K-8644 (EC50=14 nM). (S)-(-)-Bay-K-8644 (100 nM) boosts whole-cell Ca2+ currents in A7r5 smooth muscle cells but inhibits subsequent stimulation by 1 μM FPL 64176 [3]. |
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| ln Vitro |
(±)-Bay K 8644, a racemic combination of Bay K 8644, is commonly employed as an L-type Ca2+ channel agonist. Each optical isomer has the opposite effect on IBa (R(+)-Bay K 8644 as an antagonist and (S)-(-)-Bay-K-8644 as an agonist. (S)-(-)-Bay-K-8644 can suppress the inhibitory activities of two separate cyclic nucleotide pathways on IBa in guinea pig stomach myocytes[1]. The Ca2+ channel activity is boosted by 3-30 μM (S)-(-)-Bay-K-8644, an agonist of L-type Ca2+ channels (2). The interactions of two Ca2+ channel activators, (S)-(-)-Bay-K-8644 and FPL 64176, are investigated on smooth muscle L-type Ca2+ channels. FPL 64176 (300 nM) produces persistent contractions in rat tail artery strips. The contractile response is approximately 70% reduced by (S)-(-)-Bay-K-8644 (EC50=14 nM). (S)-(-)-Bay-K-8644 (100 nM) boosts whole-cell Ca2+ currents in A7r5 smooth muscle cells but inhibits subsequent stimulation by 1 μM FPL 64176 [3].
In inspiratory neurons of neonatal mice, application of (S)-(-)-Bay-K-8644 (3–30 µM) enhanced the activity of L-type Ca²⁺ channels recorded in cell-attached patches. The open probability (Popen) of the channels increased approximately 3-fold, and the activation curve was shifted by about 20 mV in the hyperpolarizing direction. In the presence of the agonist, channel open time increased, and long-lasting openings appeared. [2] Agonist-modulated channels (by (S)-(-)-Bay-K-8644 included in the pipette solution) were also potentiated during oxygen depletion (hypoxia). This potentiation was due to an increase in open time and a decrease in closed time. [2] The slope conductance of the L-type Ca²⁺ channels, identified by their sensitivity to (S)-(-)-Bay-K-8644 and dihydropyridine antagonists, was 24 pS below and 50 pS above their null potential when carrying Ba²⁺ currents. [2] |
| Cell Assay |
Experiments were performed on medullary slice preparations from neonatal mice (postnatal days 4–12) containing the functional respiratory network. Slices were continuously superfused with artificial cerebrospinal fluid (ACSF) saturated with carbogen (95% O₂, 5% CO₂) at 28°C. [2]
Single L-type Ca²⁺ channel currents were recorded in cell-attached patches from identified inspiratory neurons. Patch pipettes were filled with a solution containing 110 mM BaCl₂ and 10 mM HEPES (pH 7.4). (S)-(-)-Bay-K-8644 (3–30 µM) was either added to the bath or included in the pipette solution. Channel activity was elicited by stepping the holding potential from 0 to +60 mV (corresponding to membrane potentials from -60 to 0 mV, assuming a resting potential of -60 mV). The open probability, open times, and closed times were analyzed from recordings. Channel activity was also assessed during hypoxia induced by replacing O₂ with N₂ in the perfusate. [2] Whole-cell high-voltage-activated Ca²⁺ currents (ICa) were also recorded from inspiratory neurons using an intracellular solution containing caesium and TEA⁺ to block K⁺ channels. The effects of hypoxia on ICa were monitored. [2] |
| References |
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| Additional Infomation |
(S)-Bay-K-8644 is a methyl 2,6-dimethyl-5-nitro-4-[2-(trifluoromethyl)phenyl]-1,4-dihydropyridine-3-carboxylic acid with an (S) configuration at position 4. It is an enantiomer of (R)-Bay-K-8644.
(S)-(-)-Bay-K-8644 has been used as a pharmacological tool for the identification and characterization of L-type Ca²⁺ channels in inspiratory neurons of neonatal mice. [2] The effects of (S)-(-)-Bay-K-8644 on channel gating (increased Popen, prolonged opening time, and hyperpolarization shift of activation potential) were similar to those observed in other cell types. [2] Studies have found that the activity of L-type Ca²⁺ channels (including those regulated by S-Bay-K-8644) in these neurons is regulated by intracellular pH and cAMP levels. [2] During hypoxia, the activity of the S-Bay-K-8644-enhanced channels is further increased. [2] This study suggests that L-type Ca²⁺ channels activated by S-Bay-K-8644 may participate in the early enhancement of respiratory rhythm during hypoxia through pathways involving glutamate release and activation of metabolite glutamate receptors (mGluR1/5). [2] |
| Molecular Formula |
C16H15N2O4F3
|
|---|---|
| Molecular Weight |
356.2965
|
| Exact Mass |
356.098
|
| CAS # |
98625-26-4
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| Related CAS # |
Bay K 8644;71145-03-4;(R)-(+)-Bay-K-8644;98791-67-4
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| PubChem CID |
6603728
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| Appearance |
Light yellow to yellow solid powder
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| Density |
1.37g/cm3
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| Boiling Point |
429.2ºC at 760mmHg
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| Flash Point |
213.4ºC
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| LogP |
4.199
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
8
|
| Rotatable Bond Count |
3
|
| Heavy Atom Count |
25
|
| Complexity |
634
|
| Defined Atom Stereocenter Count |
1
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| SMILES |
CC1=C([C@@H](C(=C(N1)C)[N+](=O)[O-])C2=CC=CC=C2C(F)(F)F)C(=O)OC
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| InChi Key |
ZFLWDHHVRRZMEI-UHFFFAOYSA-N
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| 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
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| Chemical Name |
methyl 2,6-dimethyl-5-nitro-4-[2-(trifluoromethyl)phenyl]-1,4-dihydropyridine-3-carboxylate
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| Synonyms |
(S)-(-)-Bay-K-8644; (S)-(-)-Bay K-8644; (-)-BAY R-5417; (-)-BAY-R-5417; (-)-BAY-K-8644; (-)-BAY-K 8644; Bay-K 8644 (S)-(-)-; Bay-K-8644 (S)-(-)-; BAYK 8644; BAYK8644; BAYK-8644.
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| HS Tariff Code |
2934.99.9001
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| 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)
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| Solubility (In Vitro) |
DMSO : ~100 mg/mL (~280.66 mM)
H2O : < 0.1 mg/mL |
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| Solubility (In Vivo) |
Solubility in Formulation 1: 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 sonication.
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. Solubility in Formulation 2: ≥ 2.08 mg/mL (5.84 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 20.8 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 |
*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.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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