BICYCLOL

Details

Stereochemistry	ACHIRAL
Molecular Formula	C19H18O9
Molecular Weight	390.3408
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

COC(=O)C1=CC(OC)=C2OCOC2=C1C3=C(CO)C=C(OC)C4=C3OCO4

InChI

InChIKey=KXMTXZACPVCDMH-UHFFFAOYSA-N

InChI=1S/C19H18O9/c1-22-11-4-9(6-20)13(17-15(11)25-7-27-17)14-10(19(21)24-3)5-12(23-2)16-18(14)28-8-26-16/h4-5,20H,6-8H2,1-3H3

HIDE SMILES / InChI

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/19149648 | http://www.baisainuo.com/en/productinfo.asp?id=1476&big_id=987 | https://www.ncbi.nlm.nih.gov/pubmed/17253534

Bicyclol, also known as SY 801, is a hepatoprotective agent. Bicyclol upregulates transcription factor Nrf2, HO-1 expression and protects rat brains against focal ischemia. Bicyclol induces cell cycle arrest and autophagy in HepG2 human hepatocellular carcinoma cells through the PI3K/AKT and Ras/Raf/MEK/ERK pathways. Bicyclol attenuates tetracycline-induced fatty liver associated with inhibition of hepatic ER stress and apoptosis in mice. Bicyclol promotes toll-like 2 receptor recruiting inosine 5'-monophosphate dehydrogenase II to exert its anti-inflammatory effect. Phase Ⅰ~Ⅳ clinical trials and extensive application after market launch prove that, Bicyclol is suitable for the treatment of chronic viral and non-viral liver disease with elevated serum aminotransferase abnormalities, and is excellent in safety. This drug is recommended for liver protection and anti-inflammatory medication by Chinese Medical Association in Guidelines for Management of Alcoholic Fatty Liver Disease, Guidelines for Management of Non-alcoholic Fatty Liver Disease, The Guideline of Prevention and Treatment for Chronic Hepatitis B, Expert Consensus On Hepatic Inflammation and Its Prevention and other professional guidelines and consensus.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Heat shock protein beta-1 1 Target ID: CHEMBL5976 Sources: https://www.ncbi.nlm.nih.gov/pubmed/20139905	Activator 1447

Conditions

Condition	Modality	Highest Phase	Product
Fatty liver disease 10 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19149648 http://www.baisainuo.com/en/productinfo.asp?id=1476&big_id=987	Primary	Approved 8583	Bicyclol Approved Use Bicyclol is recommended for liver protection and anti-inflammatory medication by Chinese Medical Association in Guidelines for Management of Alcoholic Fatty Liver Disease, Guidelines for Management of Non-alcoholic Fatty Liver Disease, The Guideline of Prevention and Treatment for Chronic Hepatitis B, Expert Consensus On Hepatic Inflammation and Its Prevention and other professional guidelines and consensus.
Hepatitis B 59 Sources: http://adisinsight.springer.com/drugs/800007756 https://www.ncbi.nlm.nih.gov/pubmed/17253534	Primary	Approved 8583	Bicyclol Approved Use Bicyclol is recommended for liver protection and anti-inflammatory medication by Chinese Medical Association in Guidelines for Management of Alcoholic Fatty Liver Disease, Guidelines for Management of Non-alcoholic Fatty Liver Disease, The Guideline of Prevention and Treatment for Chronic Hepatitis B, Expert Consensus On Hepatic Inflammation and Its Prevention and other professional guidelines and consensus.
Hepatitis C 42 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19149648 https://www.ncbi.nlm.nih.gov/pubmed/17253534	Primary	Approved 8583	Bicyclol Approved Use Hepatitis C treatment

C_max

Value	Dose	Co-administered	Analyte	Population
122 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/31322745/	50 mg single, oral dose: 50 mg route of administration: Oral experiment type: SINGLE co-administered:		BICYCLOL plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
889.893 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/31322745/	50 mg single, oral dose: 50 mg route of administration: Oral experiment type: SINGLE co-administered:		BICYCLOL plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
8.109 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/31322745/	50 mg single, oral dose: 50 mg route of administration: Oral experiment type: SINGLE co-administered:		BICYCLOL plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

Doses

Dose	Population	Adverse events
25 mg 3 times / day multiple, oral Studied dose Dose: 25 mg, 3 times / day Route: oral Route: multiple Dose: 25 mg, 3 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/29200411/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/29200411/	Sources: https://pubmed.ncbi.nlm.nih.gov/29200411/
25 mg 3 times / day multiple, oral Studied dose Dose: 25 mg, 3 times / day Route: oral Route: multiple Dose: 25 mg, 3 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/35567757/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/35567757/	Other AEs: Death... Other AEs: Death (grade 5, 0%) Sources: https://pubmed.ncbi.nlm.nih.gov/35567757/

AEs

AE	Significance	Dose	Population
Death	grade 5, 0%	25 mg 3 times / day multiple, oral Studied dose Dose: 25 mg, 3 times / day Route: oral Route: multiple Dose: 25 mg, 3 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/35567757/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/35567757/

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1946	substrate 1193	substrate 1388

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
	CYP4F12 10 CYP2E1 729 CYP4A11 137 CYP4F2 11 CYP2C8 810 CYP4F3 1 CYP2J2 71 CYP2C19 1119 CYP1A1 389 CYP3A5 446 CYP1A2 1197 CYP2B6 776 UGT1A10 331 UGT1A6 343 UGT2B17 237 UGT2B4 278 UGT2B7 456 P-gp 2052 UGT1A7 249 UGT1A4 399 UGT2B10 131 UGT1A8 323 UGT1A1 479 UGT2B15 236 UGT1A9 423 UGT1A3 470

Drug as perpetrator

Target	Modality	Activity	Metabolite	Clinical evidence
P-gp 1932	supressor 160 Sources: https://pubmed.ncbi.nlm.nih.gov/16627975/	yes

Drug as victim

Target	Modality	Activity
CYP2C19 1119	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/37272731/ \| https://pubmed.ncbi.nlm.nih.gov/32818657/	major
CYP3A4 1946	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/37272731/ \| https://pubmed.ncbi.nlm.nih.gov/32818657/	major
UGT2B4 278	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/32818657/	major
CYP1A1 389	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/32818657/	minor
CYP2B6 776	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/32818657/	no
CYP2E1 729	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/32818657/	no
CYP4A11 137	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/32818657/	no
CYP4F12 10	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/32818657/	no
CYP4F2 11	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/32818657/	no
CYP4F3 1	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/32818657/	no
UGT1A1 479	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/32818657/	no
UGT1A10 331	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/32818657/	no
UGT1A3 470	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/32818657/	no
UGT1A6 343	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/32818657/	no
UGT1A7 249	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/32818657/	no
UGT1A8 323	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/32818657/	no
UGT1A9 423	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/32818657/	no
UGT2B10 131	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/32818657/	no
UGT2B17 237	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/32818657/	no
UGT2B7 456	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/32818657/	no
CYP1A2 1197	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/32818657/	weak
CYP2C8 810	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/32818657/	weak
CYP2C9 1193	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/32818657/	weak
CYP2D6 1388	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/32818657/	weak
CYP2J2 71	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/32818657/	weak
CYP3A5 446	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/32818657/	weak
UGT1A4 399	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/32818657/	weak
UGT2B15 236	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/32818657/	weak
P-gp 2052	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/18801310/	yes

PubMed

Title	Date	PubMed
[Protective effects of bicyclol on liver fibrosis induced by carbon tetrachloride].	2004 Dec 17	15730626
Mechanism of protective action of bicyclol against CCl-induced liver injury in mice.	2005 Aug	15998439
[Protective effects of bicyclol on alcohol-induced liver damage in mice].	2005 Dec 21	16409862
Chemoprevention of bicyclol against hepatic preneoplastic lesions.	2006 Dec	17106253
Effects of bicyclol on dimethylnitrosamine-induced liver fibrosis in mice and its mechanism of action.	2006 Jul 4	16603200
[Protective effect of bicyclol against acute fatty liver induced by tetracycline in mice].	2008 Jan	18357727
Protect effect of bicyclol on cisplatin-induced nephrotoxicity in mice.	2009 Apr	18956176
Protective effect of bicyclol on tetracycline-induced fatty liver in mice.	2009 Jul 10	19427351

Patents

Sample Use Guides

In Vivo Use Guide

Patients received bicyclol 25mg thrice daily for six months, then stopped treatment and followed up for 3 months. Oral administration of bicyclol normalized the elevated serum transaminases (ALT, AST) by approximately 50% in chronic viral hepatitis B and C, and also showed certain level of inhibiting HBV and HCV replication.

Route of Administration: Oral

In Vitro Use Guide

Bicyclol 50 umol/L induced HSP27 expression in HepG2 cells in a time-dependent manner.

Name

Type

Language

BICYCLOL

Common Name

English

4,4'-BI-1,3-BENZODIOXOLE)-5-CARBOXYLIC ACID, 5'-(HYDROXYMETHYL)-7,7'-DIMETHOXY-, METHYL ESTER

Preferred Name

English

Bicyclol [WHO-DD]

Common Name

English

Code System Code Type Description

CAS

118159-48-1