Higenamine HCl is a selective LSD1 inhibitor (IC50=1.47 μM) extracted from Aconitum. Higenamine HCl has anti~inflammatory and anti-bacterial effect. Higenamine (Norcoclaurine) can attenuate IL-1β-induced apoptosis through the ROS-mediated PI3K/Akt signaling pathway. Higenamine HCl protects brain cells from hypoxic damage. Higenamine can promote bone formation in osteoporosis through the SMAD2/3 pathway. Higenamine HCl may be utilized in study/research of cancer, inflammation, cardiorenal syndrome and other diseases.

Physicochemical Properties

Molecular Formula	C16H18CLNO3
Molecular Weight	307.774
Exact Mass	307.097
Elemental Analysis	C, 62.44; H, 5.90; Cl, 11.52; N, 4.55; O, 15.59
CAS #	11041-94-4
Related CAS #	(S)-Higenamine hydrobromide; 105990-27-0; Higenamine; 5843-65-2; (S)-Higenamine; 22672-77-1
PubChem CID	165901
Appearance	White to off-white solid powder
Boiling Point	522.4ºC at 760 mmHg
Flash Point	209.6ºC
Vapour Pressure	1.56E-11mmHg at 25°C
LogP	3.363
Hydrogen Bond Donor Count	5
Hydrogen Bond Acceptor Count	4
Rotatable Bond Count	2
Heavy Atom Count	21
Complexity	317
Defined Atom Stereocenter Count	0
SMILES	Cl[H].O([H])C1=C(C([H])=C2C([H])([H])C([H])([H])N([H])C([H])(C([H])([H])C3C([H])=C([H])C(=C([H])C=3[H])O[H])C2=C1[H])O[H]
InChi Key	SWWQQSDRUYSMAR-UHFFFAOYSA-N
InChi Code	InChI=1S/C16H17NO3.ClH/c18-12-3-1-10(2-4-12)7-14-13-9-16(20)15(19)8-11(13)5-6-17-14;/h1-4,8-9,14,17-20H,5-7H2;1H
Chemical Name	1-[(4-hydroxyphenyl)methyl]-1,2,3,4-tetrahydroisoquinoline-6,7-diol;hydrochloride
Synonyms	Higenamine HCl; norcoclaurine HCl; (+-)-Demethylcoclaurine hydrochloride; Higenamine hydrochloride
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 Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture and light.
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	β2-adrenoceptor; α1-adrenoceptor
ln Vitro	Higenamine has the ability to agonist β2-adrenoceptors. It is also a weak α2 agonist and a α1 antagonist in addition to being a strong cardiotonic and vasodilator[1]. After 24 hours of incubation, hegemone exhibits a dose-dependent reduction in intracellular dopamine content of 55.2% in PC12 cells at a concentration of 2OM. In PC12 cells, higenamine has an IC50 value of 18.2 μM for inhibiting dopamine biosynthesis. After being exposed to higenamine, dopamine levels decrease and eventually reach a minimal level in 12 to 24 hours[2].
ln Vivo	In tracheal muscle, heigemine can cause relaxation[1]. In model studies of acute thrombosis in mice and arterio-venous shunts (AV-shunts) in rats, hegigenamine exhibits antithrombotic properties. When given orally, higenamine (50 or 100 mg/kg) decreases the weight of thrombus that forms inside the AV-shunt tube in rats and improves recovery rates from the acute thrombotic challenge in mice#3.
Cell Assay	RPMI 1640 medium supplemented with 10% heat-inactivated horse serum, 5% fetal calf serum, 100 units/ml penicillin, and 100 μg/ml streptomycin is used to regularly maintain PC12 cells at 37°C. After being treated with higenamine (5-2O μM), the PC12 cells (approximately 1×105 cells/cm2) are incubated for 12 (-48) hours. PBS is used to harvest the cells (approximately 1.5–2 × 105 cells/cm2), and the pellet extract is used to measure the amount of dopamine, as well as TH and AADC activities.
Animal Protocol	Spontaneous osteoporosis SAMP6 mice model 10 mg/kg, 20 mg/kg Intraperitoneal injection (i.p.);Once daily for 60 days
References	[1]. Acta Pharmacol Sin . 2008 Oct;29(10):1187-94. [2]. Planta Med . 1999 Jun;65(5):452-5. [3]. Planta Med . 2001 Oct;67(7):619-22.
Additional Infomation	Demethylcoclaurine hydrochloride is a member of isoquinolines.

Solubility Data

Solubility (In Vitro)

DMSO: 61~100 mg/mL (198.2~324.9 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.08 mg/mL (6.76 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 (6.76 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: 100 mg/mL (324.92 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	3.2492 mL	16.2459 mL	32.4918 mL
	5 mM	0.6498 mL	3.2492 mL	6.4984 mL
	10 mM	0.3249 mL	1.6246 mL	3.2492 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.