Cinchonidine (α-Quinidine) is a cinchoni alkaloid found in cinchona and mugwort. Cinchonidine (α-Quinidine) is a building block/intermediate used in asymmetric synthesis in organic chemistry. It is a weak inhibitor of serotonin transporter (SERT). The Ki for dSERT, hSERT, hSERT I172M, hSERT S438T, and hSERT Y95F are 330, 4.2, 36, 196, and 15 μM respectively. Has antimalarial activity.

Physicochemical Properties

Molecular Formula	C19H22N2O
Molecular Weight	294.39
Exact Mass	294.173
CAS #	485-71-2
Related CAS #	485-71-2;524-54-9 (2HCl);524-57-2 (HCl);524-61-8 (sulfate);
PubChem CID	101744
Appearance	White to off-white solid powder
Density	1.2±0.1 g/cm3
Boiling Point	464.5±30.0 °C at 760 mmHg
Melting Point	204-206ºC
Flash Point	234.7±24.6 °C
Vapour Pressure	0.0±1.2 mmHg at 25°C
Index of Refraction	1.652
LogP	3.35
Hydrogen Bond Donor Count	1
Hydrogen Bond Acceptor Count	3
Rotatable Bond Count	3
Heavy Atom Count	22
Complexity	412
Defined Atom Stereocenter Count	4
SMILES	C=C[C@H]1CN2CC[C@H]1C[C@H]2[C@@H](C3=CC=NC4=CC=CC=C34)O
InChi Key	KMPWYEUPVWOPIM-KODHJQJWSA-N
InChi Code	InChI=1S/C19H22N2O/c1-2-13-12-21-10-8-14(13)11-18(21)19(22)16-7-9-20-17-6-4-3-5-15(16)17/h2-7,9,13-14,18-19,22H,1,8,10-12H2/t13-,14-,18-,19+/m0/s1
Chemical Name	(R)-quinolin-4-yl((1S,2S,4S,5R)-5-vinylquinuclidin-2-yl)methanol
Synonyms	α-Quinidine; Cinchonidine dihydrochloride, Cinchonidine sulfate, Cinchovatine, alpha-Quinidine
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: (1). This product requires protection from light (avoid light exposure) during transportation and storage.(2). Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture.
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	Serotonin Transporter (SERT, human) (Ki = 1.6 ± 0.2 μM) [1]
ln Vitro	Gongronema latifolium and Cinchona contain the cinchoni alkaloid cinchonidine (α-Quinidine). Building blocks for organic chemistry's asymmetric synthesis. Serotonin transporter (SERT) weak inhibitors: 330, 4.2, 36, 196, and 15 μM for dSERT, hSERT, hSERT I172M, hSERT S438T, and hSERT Y95F, respectively [1]. Cinchonidine exhibited stereoselective inhibitory activity against the human serotonin transporter (SERT). It competitively inhibited the uptake of [³H]-serotonin into HEK293 cells stably expressing human SERT, with a Ki value of 1.6 ± 0.2 μM. This affinity was significantly higher than that of its enantiomer, cinchonine (Ki = 3.8 ± 0.5 μM). The inhibition was concentration-dependent, with no significant cross-reactivity against dopamine transporters (DAT) or norepinephrine transporters (NET) at concentrations up to 10 μM [1]
Enzyme Assay	Radioligand binding assay: Membrane preparations from HEK293 cells expressing human SERT were incubated with [³H]-paroxetine (a selective SERT ligand) and increasing concentrations of Cinchonidine at 25°C for 60 minutes. Non-specific binding was determined in the presence of excess unlabeled paroxetine. Bound radioactivity was separated by vacuum filtration and quantified using a scintillation counter, and Ki values were calculated via nonlinear regression analysis of competition binding curves [1] - Serotonin uptake assay: HEK293-SERT cells were seeded in 24-well plates and preincubated with Cinchonidine for 15 minutes at 37°C in a CO₂ incubator. [³H]-serotonin was then added to each well at a final concentration of 50 nM, and the incubation continued for 10 minutes. The uptake reaction was terminated by washing the cells twice with ice-cold buffer. Cells were lysed, and intracellular radioactivity was measured by scintillation counting to assess the inhibitory effect of Cinchonidine on SERT-mediated serotonin transport [1]
References	[1]. Stereoselective inhibition of serotonin transporters by antimalarial compounds. Neurochem Int. 2014 Jul;73:98-106.
Additional Infomation	Cinchonidine is 8-epi-Cinchonan in which a hydrogen at position 9 is substituted by hydroxy (R configuration). A diasteroisomer of cinchonine, it occurs in the bark of most varieties of Cinchona shrubs, and is frequently used for directing chirality in asymmetric synthesis. It has a role as a metabolite. It is a cinchona alkaloid and an (8xi)-cinchonan-9-ol. It derives from a hydride of an (8S)-cinchonan. Cinchonidine has been reported in Cinchona calisaya, Cinchona, and other organisms with data available. Cinchonidine is a naturally occurring quinoline alkaloid isolated from Cinchona bark, with well-documented antimalarial activity. This study identifies it as a stereoselective inhibitor of SERT, a key target for modulating serotonergic neurotransmission. The competitive binding mode to SERT suggests potential applications in neurological disorders involving serotonin dysregulation, beyond its established antimalarial use [1]

Solubility Data

Solubility (In Vitro)

DMSO:59 mg/mL (200.41 mM) Water:<1 mg/mL Ethanol:59 mg/mL (200.41 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.5 mg/mL (8.49 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 (8.49 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 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 3: ≥ 2.5 mg/mL (8.49 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 25.0 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	3.3969 mL	16.9843 mL	33.9685 mL
	5 mM	0.6794 mL	3.3969 mL	6.7937 mL
	10 mM	0.3397 mL	1.6984 mL	3.3969 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.