Sophocarpine monohydrate, a major and naturally occuring ingredient found in Sophora alopecuroides, has a wide range of pharmacological effects. Sophocarpine exerts anti-cachectic effects by inhibiting TNF-α and IL-6 production in both RAW264.7 cells and murine primary macrophages. Sophocarpine also shows antivirus activity by inhibiting HHV-6 replication in Molt-3 cells. In addition, Sophocarpine is a potent blocker of HERG K+ channels with an IC50 of about 200 mM.

Physicochemical Properties

Molecular Formula	C15H22N2O
Molecular Weight	246.35
Exact Mass	246.173
Elemental Analysis	C, 67.63; H, 9.84; N, 10.52; O, 12.01
CAS #	145572-44-7
Related CAS #	Sophocarpine;6483-15-4
PubChem CID	115269
Appearance	Light yellow to yellow solid powder
Density	1.2±0.1 g/cm3
Boiling Point	425.4±45.0 °C at 760 mmHg
Flash Point	194.0±21.1 °C
Vapour Pressure	0.0±1.0 mmHg at 25°C
Index of Refraction	1.603
LogP	1.37
Hydrogen Bond Donor Count	0
Hydrogen Bond Acceptor Count	2
Rotatable Bond Count	0
Heavy Atom Count	18
Complexity	392
Defined Atom Stereocenter Count	4
SMILES	C1C[C@H]2CN3[C@H](CC=CC3=O)[C@@H]4[C@H]2N(C1)CCC4
InChi Key	AAGFPTSOPGCENQ-JLNYLFASSA-N
InChi Code	InChI=1S/C15H22N2O/c18-14-7-1-6-13-12-5-3-9-16-8-2-4-11(15(12)16)10-17(13)14/h1,7,11-13,15H,2-6,8-10H2/t11-,12+,13+,15-/m0/s1
Chemical Name	1H,5H,10H-Dipyrido(2,1-f:3,2,1-ij)(1,6)naphthyridin-10-one, 2,3,6,7,7a,8,13,13a,13b,13c-decahydro-, (7aS,13aR,13bR,13cS)-
Synonyms	(-)-Sophocarpine
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

Targets	Biochemical reagent; natural alkaloid
ln Vitro	Sophoridine (0-500 μM; 48 hours) has an IC50 value of roughly 20 μM to 200 μM, which significantly inhibits the growth of human pancreatic cancer, gastric cancer, liver cancer, colon cancer, gallbladder cancer, and prostate cancer cells [1]. Sophoridine (0-20 μM; 48 hours) increased the S-phase cell population in Miapaca-2 cells from 26.23% (control) to 38.67% and in PANC-1 cells from 29.56% (control). control) increased to 39.16%, approximately 1.5 times and 1.3 times respectively [1]. In contrast, sophoridin (0–20 μM; 48 hours) significantly lowers bcl-2 and bcl–xl levels while significantly raising the Bax/Bcl-2 ratio [1]. It also significantly raises bad and bax levels. In vitro activity: Sophocarpine exerts anti-cachectic effects by inhibiting TNF-α and IL-6 production in both RAW264.7 cells and murine primary macrophages. Sophocarpine also shows antivirus activity by inhibiting HHV-6 replication in Molt-3 cells. In addition, Sophocarpine is a potent blocker of HERG K+ channels with an IC50 of about 200 mM.
ln Vivo	Sophoridine (ip; 20 or 40 mg/kg; 21 days) suppresses the growth of pancreatic tumors that have been xenografted [1]. The present study aims to access the effects of sophora alkaloids on the production of pro-inflammatory cytokines and evaluate their therapeutic efficiency on cachexia. The comparative study showed that all sophora alkaloids tested here, including matrine, oxymatrine, sophocarpine, sophoramine, and sophoridine, inhibited TNF-alpha and IL-6 production in both RAW264.7 cells and murine primary macrophages, and sophocarpine showed the most potent inhibitory effect among them. Quantification of TNF-alpha and IL-6 mRNA in RAW264.7 cells by real-time RT-PCR revealed that both sophocarpine and matrine suppressed TNF-alpha and IL-6 expression and sophocarpine has stronger suppressing potency than matrine. Inoculation (s.c.) of colon26 adenocarcinoma cells into BALB/c mice induced cachexia, as evidenced by progressive weight loss, reduction in food intake, wasting of gastrocnemius muscle and epididymal fat, and increase in serum levels of TNF-alpha and IL-6. Administration of 50 mg/kg/d sophocarpine or matrine for 5 days from the onset of cachexia did not inhibit the tumor growth but resulted in attenuation of cachexia symptoms. Furthermore, sophocarpine and matrine decreased the serum levels of TNF-alpha and IL-6, and sophocarpine showed a better therapeutic effect than matrine. These results suggest that sophocarpine and matrine exert anti-cachectic effects probably through inhibition of TNF-alpha and IL-6. [2] Administration of 50 mg/kg/d sophocarpine for 5 days from the onset of cachexia does not inhibit the tumor growth but results in attenuation of cachexia symptoms in colon26 adenocarcinoma xenograft BALB/c mice. LD50: Mice 63.94mg/kg (i.v.).
Enzyme Assay	The virostatic activity of sophocarpines and gancyclovir (GCV) was tested using HHV-6 Z29 strain and Molt-3 cells. The cytotoxic (IC(50)) and the antiviral (ED(50)) values were first experimentally determined and selective indices (SI) were then calculated. The SI values for sophocarpines 1 and 2 and GCV were in the order 184, 183, and 23, respectively. Though preliminary, these findings indicate that sophocarpines have the potential to inhibit HHV-6 replication[3]. Human ether-à-go-go-related gene (HERG) encodes the rapid component of the cardiac delayed rectifier K+ current, which has an important role in the repolarization of the cardiac action potential. QT interval prolongation through HERG channel inhibition is associated with a risk of torsade de pointes arrhythmias and is a major challenge for drug development. The effects of the novel antiviral drug sophocarpine (SC) were examined on stably expressed HERG channels in human embryonic kidney (HEK293) cells using a whole-cell patch clamp technique, Western blot analysis and immunofluorescence experiments. SC inhibited HERG channels in a concentration-dependent manner, with an IC50 of 100-300 microM. SC significantly accelerated channel inactivation, recovery from inactivation and onset of inactivation. In addition, it had no effect on channel activation and deactivation. Based on Western blot and immunofluorescence results, SC had no significant effect on the expression of HERG protein. In summary, SC is a potent blocker of HERG K+ channels that functions by changing the channel inactivation kinetics. In addition, SC has no effect on the generation and trafficking of HERG protein[4].
Cell Assay	Cell viability assay [1] Cell Types: Normal cells: IOSE144, HL-7702 and LO2, BEAS-2B, GES-1, HEK 293 T, HPDE, FHC, human cancer cells: PANC-1, Mapaca-1, hepG2, SGC-7901, CBC-SD, SGC-996, PC-3, MKN-45, MGC-803, Hela and HCT116 cell Tested Concentrations: 0, 3.9, 7.8, 15.5, 31, 62.5, 125, 250, 500 μM Incubation Duration: 48 hrs (hours) Experimental Results: demonstrated the most effective cytotoxicity against cancer cells. Cell cycle analysis [1] Cell Types: PANC-1 cells; Miapca-2 cells Tested Concentrations: 20 μM Incubation Duration: 48 hrs (hours) Experimental Results: Resulting in S phase population accumulation. Western Blot Analysis [1] Cell Types: PANC-1 cells; Miapca-2 cells Tested Concentrations: 20 μM Incubation Duration: 48 hrs (hours) Experimental Results: Induction of activation of intrinsic apoptotic pathway.
Animal Protocol	50 mg/kg; Mice Animal/Disease Models: BALB/c homozygous (nu/nu) nude mice [1] Doses: 20 or 40 mg/kg Route of Administration: intraperitoneal (ip) injection; 20 or 40 mg/kg; 21-day Experimental Results: Xenograft pancreatic tumor mass reduction.
Toxicity/Toxicokinetics	mouse LD50 oral 243 mg/kg Zhongguo Yaoxue Zazhi. Chinese Pharmacuetical Journal., 27(201), 1992 mouse LD50 intravenous 46800 ug/kg Yaowu Fenxi Zazhi. Journal of Pharmaceutical Analysis., 6(96), 1986 mouse LD50 intraperitoneal 64300 ug/kg Zhongguo Yaoli Xuebao. Acta Pharmacologica Sinica. Chinese Journal of Pharmacology., 8(153), 1987 [PMID:2959003]
References	[1]. J Exp Clin Cancer Res. 2017 Sep 11;36(1):124. [2]. Int Immunopharmacol.2008 Dec 20;8(13-14):1767-72. [2]. Phytother Res.2002 Mar;16(2):154-6. [4]. Biol Pharm Bull.2008 Apr;31(4):627-32.
Additional Infomation	Sophocarpine is an alkaloid. Sophocarpine has been reported in Daphniphyllum oldhamii, Daphniphyllum pentandrum, and other organisms with data available. Sophoridine has been reported in Euchresta japonica, Leontice leontopetalum, and other organisms with data available. Tetracyclic bis-quinolizidine alkaloids found in the family LEGUMINOSAE, mainly in the genus SOPHORA. Background: Pancreatic cancer is generally acknowledged as the most common primary malignant tumor, and it is known to be resistant to conventional chemotherapy. Novel, selective antitumor agents are pressingly needed. Methods: CCK-8 and colony formation assay were used to investigate the cell growth. Flow cytometry analysis was used to evaluate the cell cycle and cell apoptosis. The peroxide-sensitive fluorescent probe DCFH-DA was used to measure the intracellular ROS levels. Western blot assay was used to detect the levels of cell cycle and apoptosis related proteins. Xenografts in nude mice were used to evaluate the effect of Sophoridine on pancreatic cancer cell in vivo. Results: Sophoridine killed cancer cells but had low cytotoxicity to normal cells. Pancreatic cancer cells were particularly sensitive. Sophoridine inhibited the proliferation of pancreatic cancer cells and induced cell cycle arrest at S phase and mitochondrial-related apoptosis. Moreover, Sophoridine induced a sustained activation of the phosphorylation of ERK and JNK. In addition, Sophoridine provoked the generation of reactive oxygen species (ROS) in pancreatic cancer cells. Finally, in vivo, Sophoridine suppressed tumor growth in mouse xenograft models. Conclusion: These findings suggest Sophoridine is promising to be a novel, potent and selective antitumor drug candidate for pancreatic cancer.[1]

Solubility Data

Solubility (In Vitro)

DMSO:49 mg/mL (198.9 mM) Water:49 mg/mL (198.9 mM) Ethanol:49 mg/mL (198.9 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.5 mg/mL (9.46 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 (9.46 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 (9.46 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	4.0593 mL	20.2963 mL	40.5927 mL
	5 mM	0.8119 mL	4.0593 mL	8.1185 mL
	10 mM	0.4059 mL	2.0296 mL	4.0593 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.