Tetrandrine (NSC-77037)

Alias: NSC 77037; Sinomenine A; d-tetrandrine; Fanchinine; Tetrandrine; NSC-77037; NSC77037; (S,S)-(+)-tetrandrine; TTD.
Cat No.:V1232 Purity: ≥98%
Tetrandrine (also called Fanchinine; Sinomenine A; d-tetrandrine; formerly NSC-77037), a bis-benzylisoquinoline alkaloid derived from Stephania tetrandra, is a novel and potent calcium channel blocker which inhibits voltage-gated Ca2+ current (ICa) and Ca2+-activated K+ current.
Tetrandrine (NSC-77037) Chemical Structure CAS No.: 518-34-3
Product category: Histamine Receptor
This product is for research use only, not for human use. We do not sell to patients.
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Purity & Quality Control Documentation

Purity: ≥98%

Product Description

Tetrandrine (also called Fanchinine; Sinomenine A; d-tetrandrine; formerly NSC-77037), a bis-benzylisoquinoline alkaloid derived from Stephania tetrandra, is a novel and potent calcium channel blocker which inhibits voltage-gated Ca2+ current (ICa) and Ca2+-activated K+ current. Tetrandrine inhibits the L-type calcium channels (IC50 = 0.3-8 µM) and T-type calcium channels (IC50 = 2.5-20 µM). Moreover, the Ca2+-activated K+ channel (Kd=0.2 µM) is strongly blocked by it. In isolated nerve terminals of the rat neurohypophysis, tetrandrine inhibits voltage-gated Ca2+ currents with an IC50 of 10.1 mM. With an IC50 of 0.21 mM, tetrandrine is a high-affinity blocker of the type II, maxi-Ca(2+)-activated K+ channel of the rat neurohypophysial terminals.

Biological Activity I Assay Protocols (From Reference)
Targets
Ca2+ current; K+ current
ln Vitro

In vitro activity: Patch-clamp techniques are used to study the effects of Tetrandrine (NSC-77037), a bis-benzyl-isoquinoline alkaloid, on voltage-gated Ca2+ currents (ICa) and Ca2+-activated K+ currents (IK(Ca)) and channels in isolated nerve terminals of the rat neurohypophysis. External Tetrandrine (NSC-77037) inhibits the non-inactivating component of ICa in a voltage- and dose-dependent manner, with an IC50=10.1μM. Tetrandrine (NSC-77037) has an IC50=0.21 μM and reduces the channel-open probability within bursts[1]. Tetrandrine is applied to Huh7, HCCLM9, and Hep3B cells at concentrations of 0 (DMSO), 0.5, 1, 2, or 4 μM for a duration of 24 hours in order to assess the impact on HCC cells. Tetrandrine virtually has no effect on the inhibition of HCC cell proliferation at 0.5-2 μM, according to the cell proliferation assay. On the other hand, HCC cell migration is dose-dependently inhibited by telandrine (NSC-77037). Moreover, a transwell and wound-healing assay demonstrates that 2 μM Tetrandrine strongly prevents HCC cell invasion and migration[2].

ln Vivo
In order to assess Tetrandrine (NSC-77037)'simpacton the prevention of tumor metastasis in vivo, athymic nude mice are used to create HCCLM9 subcutaneous tumor xenograft models. Nude mice are given either vehicle or Tetrandrine (NSC-77037) (30 mg/kg) orally every other day for 37 days, or until the tumor volume reaches about 50 mm3. Treatment with tectrandrine (NSC-77037) decreases the weight and volume of the tumor[2].
Cell Assay
In a 96-well plate, Huh7, HCCLM9, and Hep3B cells are seeded at a density of 5 × 103 cells/well. For twenty-four hours, the cells are exposed to Tetrandrine (NSC-77037) at the indicated concentrations (0–4 μM). After staining the cells for one to two hours with 20 μL of MTS, the plates are read at 490 nm using a BioTek ELx800[2].
Animal Protocol
Male athymic BALB/c nu/nu SPF mice, weighing between 18 and 20 g at body weight, are employed. They are four weeks old. Each mouse has five million reconstituted HCCLM9 WT and ATG7 KO cells placed subcutaneously in its right flank, using 0.2 mL of PBS. The tumor-bearing mice are randomly assigned to treatment and control groups (n = 6) once the tumor volume reaches about 50 mm3. For 37 days, oral injections of the vehicle (0.5% methylcellulose) and Tetrandrine (30 mg/kg of body weight) are given to the control and treatment groups every other day. Every day during the course of treatment, the tumor volumes are measured and computed.
Mice
References

[1]. Tetrandrine blocks a slow, large-conductance, Ca(2+)-activated potassium channel besides inhibiting a non-inactivating Ca2+ current in isolated nerve terminals of the rat neurohypophysis. Pflugers Arch. 1992 Sep;421(6):558-65.

[2]. The plant alkaloid tetrandrine inhibits metastasis via autophagy-dependent Wnt/β-catenin and metastatic tumor antigen 1 signaling in human liver cancer cells. J Exp Clin Cancer Res. 2018 Jan 15;37(1):7.

These protocols are for reference only. InvivoChem does not independently validate these methods.
Physicochemical Properties
Molecular Formula
C38H42N2O6
Molecular Weight
622.75
Exact Mass
622.3
Elemental Analysis
C, 73.29; H, 6.80; N, 4.50; O, 15.41
CAS #
518-34-3
Related CAS #
518-34-3
Appearance
Solid powder
SMILES
CN1CCC2=CC(=C3C=C2[C@@H]1CC4=CC=C(C=C4)OC5=C(C=CC(=C5)C[C@H]6C7=C(O3)C(=C(C=C7CCN6C)OC)OC)OC)OC
InChi Key
WVTKBKWTSCPRNU-KYJUHHDHSA-N
InChi Code
InChI=1S/C38H42N2O6/c1-39-15-13-25-20-32(42-4)34-22-28(25)29(39)17-23-7-10-27(11-8-23)45-33-19-24(9-12-31(33)41-3)18-30-36-26(14-16-40(30)2)21-35(43-5)37(44-6)38(36)46-34/h7-12,19-22,29-30H,13-18H2,1-6H3/t29-,30-/m0/s1
Chemical Name
(1S,14S)-9,20,21,25-tetramethoxy-15,30-dimethyl-7,23-dioxa-15,30-diazaheptacyclo[22.6.2.23,6.18,12.114,18.027,31.022,33]hexatriaconta-3(36),4,6(35),8,10,12(34),18,20,22(33),24,26,31-dodecaene
Synonyms
NSC 77037; Sinomenine A; d-tetrandrine; Fanchinine; Tetrandrine; NSC-77037; NSC77037; (S,S)-(+)-tetrandrine; TTD.
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)
Solubility Data
Solubility (In Vitro)
DMSO: 5~12 mg/mL (8.0~19.3 mM)
Water: <1 mg/mL
Ethanol: <1 mg/mL
Solubility (In Vivo)
Solubility in Formulation 1: ≥ 0.5 mg/mL (0.80 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 5.0 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: ≥ 0.5 mg/mL (0.80 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 5.0 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.

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Solubility in Formulation 3: ≥ 0.5 mg/mL (0.80 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 5.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.


Solubility in Formulation 4: 10 mg/mL (16.06 mM) in 50% PEG300 50% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

 (Please use freshly prepared in vivo formulations for optimal results.)
Preparing Stock Solutions 1 mg 5 mg 10 mg
1 mM 1.6058 mL 8.0289 mL 16.0578 mL
5 mM 0.3212 mL 1.6058 mL 3.2116 mL
10 mM 0.1606 mL 0.8029 mL 1.6058 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.

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Using the equation C1V1 = C2V2, where C1=10 mM, C2=25 μM, V2=25 ml and V1 is the unknown:
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Note: Chemical formula is case sensitive: C12H18N3O4  c12h18n3o4
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In vivo Formulation Calculator (Clear solution)
Step 1: Enter information below (Recommended: An additional animal to make allowance for loss during the experiment)
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Calculation results

Working concentration mg/mL;

Method for preparing DMSO stock solution mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.

Method for preparing in vivo formulation:Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O,mix and clarify.

(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
             (2) Be sure to add the solvent(s) in order.

Clinical Trial Information
NCT Number Recruitment interventions Conditions Sponsor/Collaborators Start Date Phases
NCT05697029 Not yet recruiting Drug: Tetrandrine COVID-19 Peking University Third
Hospital
December 31, 2023 Phase 4
NCT05245448 Not yet recruiting Drug: Tetrandrine
Drug: Placebo
Rheumatoid Arthritis Peking University People's
Hospital
February 22, 2022 Not Applicable
Biological Data
  • Tetrandrine inhibits HCC cell invasion and migration. J Exp Clin Cancer Res . 2018 Jan 15;37(1):7.
  • Tetrandrine prevented HCC cell EMT. J Exp Clin Cancer Res . 2018 Jan 15;37(1):7.
  • Tetrandrine-inhibited HCC cell migration is associated with autophagy. J Exp Clin Cancer Res . 2018 Jan 15;37(1):7.
  • Autophagy-dependent Wnt/β-catenin pathway was involved in tetrandrine-inhibition of HCC cell migration. J Exp Clin Cancer Res . 2018 Jan 15;37(1):7.
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