BMS-191011 is an opener (activator) of large-conductance Ca²⁺-activated potassium channels (BKCa channels). [2]

BMS-191011 (20 or 40 µM) causes potentiation in Panc-1 cells and opens BK channels in IGR39 cells [3].

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In whole-cell patch-clamp recordings, BMS-191011 (20–40 μM) activated BK channels in less than 50% of IGR39 (primary melanoma) cells, with a modest degree of activation. [3]
- In IGR39 cells, BMS-191011 also promoted the activation of a voltage-independent K⁺ conductance at negative voltages, not responsive to paxilline, possibly mediated by KCa3.1 channels. [3]
- In Panc-1 (pancreatic duct adenocarcinoma) cells, BMS-191011 resulted in only a slight activation of outward currents. [3]
- Because of the limited activity of BMS-191011 on BK-mediated currents, the compound was not employed in further assays (cell viability, migration, proliferation). [3]

Rat retinal arterioles are dilated by BMS-191011 (iv; 10-100 µg/kg; once) through in vivo activation of iberiotoxin-sensitive BK(Ca) channels [2].

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In anesthetized male Wistar rats (8–10 weeks old), intravenous infusion of BMS-191011 at doses of 10, 30, and 100 μg/kg/min (administered via continuous infusion) significantly increased the diameter of retinal arterioles in a dose-dependent manner. [2]
- The vasodilatory effect of BMS-191011 on retinal arterioles was significantly attenuated by intravitreal injection of iberiotoxin (20 pmol/eye), a selective BKCa channel inhibitor, indicating that the effect is mediated via BKCa channel activation. [2]
- BMS-191011 at the tested doses (up to 100 μg/kg/min) did not significantly alter mean arterial pressure or heart rate. [2]
- Preliminary studies indicated that a higher dose (20 mg/kg, i.v.) of BMS-191011 dramatically decreased blood pressure. [2]

Cell Viability Assay[3]
Cell Types: IGR39 and Panc-1 Cell
Tested Concentrations: 20 or 40 µM
Incubation Duration:
Experimental Results: Activation of BK channels in less than 50% of IGR39 cells and less than twice as high in Panc-1 cells of enhancement. Promotes activation of voltage-independent K+ conductance at negative voltages.

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Whole-cell patch-clamp recordings were performed on IGR39, IGR37, and Panc-1 cells. Cells were transferred to Petri dishes and recordings were performed 24–36 h later. Glass pipettes (3–5 MΩ resistance) were filled with intracellular solution containing (in mM): 8 NaCl, 100 K-aspartate, 40 KCl, 2 CaCl₂, 10 EGTA, 10 HEPES (pH 7.3, free Ca²⁺ ≈ 20 nM). Extracellular solutions were as described. The voltage protocol consisted of 500 ms steps from −80 to +120 mV in 20 mV increments from a holding potential of −50 mV. Currents were filtered at 10 kHz and digitized at 50 kHz. [3]
- BMS-191011 was applied at 20–40 μM. In IGR39 cells, less than 50% of cells responded with BK channel activation. In Panc-1 cells, only slight activation was observed. [3]
- No cell viability, proliferation, or migration assays were performed with BMS-191011 due to its low potency. [3]

Animal/Disease Models: Male Wistar rats (8 to 10 weeks old) were treated with tetrodotoxin (50 µg/kg, intravenously (iv) (iv)(iv) (iv)) [2]
Doses: 10-100 µg/kg
Route of Administration: intravenously (iv) (iv)(iv); i.v. injection. 10-100 micrograms/kg; primary
Experimental Results:the diameter of retinal arterioles increases, but has no significant effect on mean arterial pressure and heart rate.

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Male Wistar rats (8–10 weeks old) were anesthetized with pentobarbital sodium (50 mg/kg, intraperitoneal). A tracheotomy was performed for artificial ventilation. Catheters were inserted into the femoral and jugular veins for drug administration. The left femoral artery was cannulated for measurement of arterial pressure. [2]
- To eliminate nerve activity and prevent eye movement, rats were treated with tetrodotoxin (50 μg/kg, intravenous) under artificial ventilation. A mixture of adrenaline and noradrenaline (9:1) was continuously infused to maintain systemic circulation. [2]
- BMS-191011 was dissolved in dimethyl sulfoxide (DMSO) and further diluted in a solution of cremophore and saline (5:43). The drug was infused intravenously via a syringe pump at doses of 10, 30, and 100 μg/kg/min. [2]
- For BKCa channel inhibition, iberiotoxin (20 pmol in 10 μL saline) was injected into the vitreous cavity of the left eye using a 32-gauge needle inserted approximately 1 mm behind the corneal limbus. [2]
- Fundus images were captured using a digital camera equipped with a bore scope-type objective lens. Sodium fluorescein (10% solution, 0.8 mL/kg) and brilliant blue 6B (5% solution, 0.8 mL/kg) were injected intravenously to enhance blood vessel contrast. [2]

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Male Wistar rats (8–10 weeks old) were anesthetized with pentobarbital sodium (50 mg/kg, intraperitoneal). A tracheotomy was performed for artificial ventilation. Catheters were inserted into the femoral and jugular veins for drug administration. The left femoral artery was cannulated for measurement of arterial pressure. [2]
- To eliminate nerve activity and prevent eye movement, rats were treated with tetrodotoxin (50 μg/kg, intravenous) under artificial ventilation. A mixture of adrenaline and noradrenaline (9:1) was continuously infused to maintain systemic circulation. [2]
- BMS-191011 was dissolved in dimethyl sulfoxide (DMSO) and further diluted in a solution of cremophore and saline (5:43). The drug was infused intravenously via a syringe pump at doses of 10, 30, and 100 μg/kg/min. [2]
- For BKCa channel inhibition, iberiotoxin (20 pmol in 10 μL saline) was injected into the vitreous cavity of the left eye using a 32-gauge needle inserted approximately 1 mm behind the corneal limbus. [2]
- Fundus images were captured using a digital camera equipped with a bore scope-type objective lens. Sodium fluorescein (10% solution, 0.8 mL/kg) and brilliant blue 6B (5% solution, 0.8 mL/kg) were injected intravenously to enhance blood vessel contrast. [2]

At the tested doses (10–100 μg/kg/min), no significant adverse effects on mean arterial pressure or heart rate were observed. [2]
- Preliminary studies indicated that a higher dose (20 mg/kg, intravenous) caused a dramatic decrease in blood pressure. [2]

[1]. 3-[(5-Chloro-2-hydroxyphenyl)methyl]-5-[4-(trifluoromethyl)phenyl ]-1,3,4-oxadiazol-2(3H)-one, BMS-191011: opener of large-conductance Ca(2+)-activated potassium (maxi-K) channels, identification, solubility, and SAR. J Med Chem. 2007 Fe.

[2]. BMS-191011, an opener of large-conductance Ca2+-activated potassium channels, dilates rat retinal arterioles in vivo. Biol Pharm Bull. 2011;34(1):150-2.

[3]. NS-11021 Modulates Cancer-Associated Processes Independently of BK Channels in Melanoma and Pancreatic Duct Adenocarcinoma Cell Lines. Cancers (Basel). 2021 Dec 6;13(23):6144.

3-[(5-chloro-2-hydroxyphenyl)methyl]-5-[4-(trifluoromethyl)phenyl]-1,3,4-oxadiazol-2-one is a member of the (trifluoromethyl)benzene class of compounds.

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BMS-191011 is a selective opener of large-conductance Ca²⁺-activated potassium (BKCa) channels. [2]
- This study demonstrates for the first time that BMS-191011 dilates rat retinal arterioles in vivo via activation of iberiotoxin-sensitive BKCa channels, without affecting systemic blood pressure at vasoactive doses. [2]
- The vasodilator effect of BMS-191011 on retinal arterioles was significantly attenuated by intravitreal iberiotoxin, while the effect of NS 1619 (another BKCa channel opener) was not affected, suggesting that BMS-191011 may be more selective for BKCa channels in retinal vessels. [2]
- Selective BKCa channel openers such as BMS-191011 may have therapeutic potential for improving retinal circulation in diseases such as diabetic retinopathy and glaucoma, with fewer cardiovascular side effects compared to non-selective vasodilators. [2]

C16H10CLF3N2O3

370.71

370.033

C, 51.84; H, 2.72; Cl, 9.56; F, 15.37; N, 7.56; O, 12.95

202821-81-6

10474339

White to off-white solid powder

1.516g/cm3

443.965ºC at 760 mmHg

222.302ºC

0mmHg at 25°C

1.598

3.929

1

7

3

25

535

0

QKOWACXSXTXRKA-UHFFFAOYSA-N

InChI=1S/C16H10ClF3N2O3/c17-12-5-6-13(23)10(7-12)8-22-15(24)25-14(21-22)9-1-3-11(4-2-9)16(18,19)20/h1-7,23H,8H2

3-[(5-chloro-2-hydroxyphenyl)methyl]-5-[4-(trifluoromethyl)phenyl]-1,3,4-oxadiazol-2-one

BMS 191011 BMS191011BMS-191011 UNII-LW7MXS978N Bms-a

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO : ~125 mg/mL (~337.19 mM)

Solubility in Formulation 1: ≥ 2.08 mg/mL (5.61 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.

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Solubility in Formulation 2: ≥ 2.08 mg/mL (5.61 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 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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