TETRANDRINE, (±)-

Possibly Marketed Outside US

Details

Stereochemistry	RACEMIC
Molecular Formula	C38H42N2O6
Molecular Weight	622.7499
Optical Activity	( + / - )
Defined Stereocenters	2 / 2
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

[H][C@]12CC3=CC=C(OC4=CC(C[C@]5([H])N(C)CCC6=CC(OC)=C(OC)C(OC7=CC1=C(CCN2C)C=C7OC)=C56)=CC=C4OC)C=C3

InChI

InChIKey=WVTKBKWTSCPRNU-KYJUHHDHSA-N

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

HIDE SMILES / InChI

Description
Sources: http://cbapharma.com/CBT1/cbt1.html | https://www.ncbi.nlm.nih.gov/pubmed/29334999 | https://www.ncbi.nlm.nih.gov/pubmed/29101806 | https://www.ncbi.nlm.nih.gov/pubmed/29061791

Tetrandrine, isolated from the root of Stephania tetrandra S Moore, is a traditional Chinese clinical agent for silicosis, autoimmune disorders, inflammatory pulmonary diseases, cardiovascular diseases and hypertension. Tetrandrine is a potent MDR-reversing agent and is an ABCB1/ABCC1 inhibitor. Tetrandrine (CBT-1) is being developed by CBA Pharma, as an adjunctive therapy to chemotherapy in various cancer types with multiple drug resistance (MDR), including acute myelogenous leukemia , Breast, Non-Hodgkin’s Lymphoma, Hodgkin’s disease, Non-Small Cell Lung Cancer, Multiple Myeloma, Gallbladder, Pancreatic, Gastrointestinal Tract, Small Cell Lung Cancer, Bladder, Head & Neck, and Sarcoma.

CNS Activity

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Multidrug resistance protein 1 8 Target ID: P08183 Gene ID: 5243.0 Gene Symbol: ABCB1 Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/14666379 \| https://www.ncbi.nlm.nih.gov/pubmed/26548759	Inhibitor 8297
Multidrug resistance-associated protein 1 15 Target ID: P33527\|\|\|Q9UQ99 Gene ID: 4363.0 Gene Symbol: ABCC1 Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/26548759	Inhibitor 8297

Conditions

Condition	Modality	Highest Phase	Product
Non-small cell lung cancer 206 Sources: https://www.ncbi.nlm.nih.gov/pubmed/23675254	Palliative	Phase III 656	Unknown Approved Use Unknown
Nasopharyngeal carcinoma 8 Sources: https://www.ncbi.nlm.nih.gov/pubmed/29061791	Palliative	Phase II 1132	Unknown Approved Use Unknown
Tuberculosis 83 Sources: https://www.ncbi.nlm.nih.gov/pubmed/25887373	Palliative	Basic research	Unknown Approved Use Unknown
Osteosarcoma 22 Sources: https://www.ncbi.nlm.nih.gov/pubmed/26548759	Palliative	Phase I 428	Unknown Approved Use Unknown

PubMed

Title	Date	PubMed
Studies on the calcium antagonistic action of tetrandrine: XIII. Protective effect of tetrandrine on myocardial hypoxia and necrosis induced by isoproterenol in rats.	1986	3712522
Effect of tetrandrine on proto-oncogene c-fos expression in rat cerebrum.	1997 Jul	10072926
Combination of tetrandrine as a potential-reversing agent with daunorubicin, etoposide and cytarabine for the treatment of refractory and relapsed acute myelogenous leukemia.	2006 Apr	16219352
Studies on alkaloids binding to GC-rich human survivin promoter DNA using positive and negative ion electrospray ionization mass spectrometry.	2008 Mar	17968851
Anticancer effect of tetrandrine on primary cancer cells isolated from ascites and pleural fluids.	2008 Sep 8	18495333
Protective effect of tetrandrine on doxorubicin-induced cardiotoxicity in rats.	2010 May-Jun	20845809
Tetrandrine down-regulates ERK/NF-κB signaling and inhibits activation of mesangial cells.	2011 Dec	22001142
Pulmonary toxicity and metabolic activation of tetrandrine in CD-1 mice.	2011 Dec 19	21992520
CYP3A5 mediates bioactivation and cytotoxicity of tetrandrine.	2016 Jul	26302866
Tetrandrine induces programmed cell death in human oral cancer CAL 27 cells through the reactive oxygen species production and caspase-dependent pathways and associated with beclin-1-induced cell autophagy.	2017 Jan	26822499

Patents

Sample Use Guides

In Vivo Use Guide

(50 mg caps) 500 mg/m2/day x 7 + paclitaxel 135 mg/m2 + carboplatin AUC 6

Route of Administration: Oral

In Vitro Use Guide

It was investigated the effect of combined treatment of irradiation and maximum non-cytotoxic doses of tetrandrine on the nasopharyngeal carcinoma cell lines CNE1 and CNE2. The maximum non-cytotoxic doses of tetrandrine in CNE1 and CNE2 cells were assessed using the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. The maximum non-cytotoxic doses of tetrandrine in CNE1 and CNE2 cells were 1.5 μmol/L and 1.8 μmol/L, respectively. When cells were exposed to irradiation and the maximum non-cytotoxic doses of tetrandrine, the survival fraction was decreased.

Name

Type

Language

TETRANDRINE, (±)-

Common Name

English

DL-TETRANDRINE

Common Name

English

NSC-91771

Code

English

BERBAMAN, 6,6',7,12-TETRAMETHOXY-2,2'-DIMETHYL-, (1.BETA.)-(±)-

Common Name

English

(±)-TETRANDRINE

Common Name

English

16H-1,24:6,9-DIETHENO-11,15-METHENO-2H-PYRIDO(2',3':17,18)(1,11)DIOXACYCLOEICOSINO(2,3,4-IJ)ISOQUINOLINE, 3,4,4A,5,16A,17,18,19-OCTAHYDRO-12,21,22,26-TETRAMETHOXY-4,17-DIMETHYL-, (4AR,16AR)-REL-

Systematic Name

English

Code System Code Type Description

FDA UNII

VS4W77H3SD