GAL-021 is a potent BKCa channel blocker. GAL-021 inhibits KCa1.1 in GH3 cells. GAL-021 is a novel respiratory control modulator based on selective modification of the amitriptyline pharmacophore. GAL-021 increases minute ventilation in rats and non-human primates.

Physicochemical Properties

Molecular Formula	C11H22N6O
Molecular Weight	254.331981182098
Exact Mass	254.185
CAS #	1380341-99-0
Related CAS #	GAL-021 sulfate;1380342-00-6
PubChem CID	57340959
Appearance	White to off-white solid powder
LogP	2.9
Hydrogen Bond Donor Count	2
Hydrogen Bond Acceptor Count	7
Rotatable Bond Count	8
Heavy Atom Count	18
Complexity	202
Defined Atom Stereocenter Count	0
SMILES	CCCNC1=NC(N(OC)C)=NC(NCCC)=N1
InChi Key	FJNLCHNQVJVCPY-UHFFFAOYSA-N
InChi Code	InChI=1S/C11H22N6O/c1-5-7-12-9-14-10(13-8-6-2)16-11(15-9)17(3)18-4/h5-8H2,1-4H3,(H2,12,13,14,15,16)
Chemical Name	2-N-methoxy-2-N-methyl-4-N,6-N-dipropyl-1,3,5-triazine-2,4,6-triamine
Synonyms	GAL021 GAL 021 GAL-021
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

ln Vitro	As a novel respiratory control modulator, GAL-021 is being developed to protect patients against respiratory impairment brought on by opioids and other modalities, while also preserving respiratory drive. GAL-021 inhibited single-channel KCa1.1 activity in GH3 cells through the use of an inside-out patch in a concentration-dependent manner. At 30 μM, the inhibition was 35% or less when measured against 12 distinct cardiac ion channels. At 10 μM, there was no discernible kinase inhibition. Adenosine A1 (65% I), A2A (79% I, IC50 ~5μM), and A3 (93% I; IC50 ~5μM) at 30 μM concentration showed interactions in a radioligand binding experiment. (characterized as greater than 50% displacement of radioligand at 1 μM) receptor, 5-HT2B receptor (60% I; IC50 ~30 μM) [1].
ln Vivo	GAL-021 is administered intravenously to rats and nonhuman primates to lessen opioid-induced respiratory depression; however, it does not impact rat analgesia. Rats' ventilation-induced activation of GAL-021 is reduced when the carotid sinus nerve is severed. When animals are deficient in the pore-forming alpha subunit of KCa 1.1 channels, GAL-021 ventilatory stimulation is reduced [1].
References	[1]. Identification and Characterization of GAL-021 as a Novel Breathing Control Modulator. Anesthesiology. 2015 Nov;123(5):1093-104. [2]. GAL-021, a new intravenous BKCa-channel blocker, is well tolerated and stimulates ventilation in healthy volunteers. Br J Anaesth. 2014 Nov;113(5):875-83.

Solubility Data

Solubility (In Vitro)

DMSO : ≥ 30 mg/mL (~117.96 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.08 mg/mL (8.18 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. Solubility in Formulation 2: ≥ 2.08 mg/mL (8.18 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in 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 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 3: ≥ 2.08 mg/mL (8.18 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.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	3.9319 mL	19.6595 mL	39.3190 mL
	5 mM	0.7864 mL	3.9319 mL	7.8638 mL
	10 mM	0.3932 mL	1.9659 mL	3.9319 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.