ACOLBIFENE

Investigational

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C29H31NO4
Molecular Weight	457.5607
Optical Activity	UNSPECIFIED
Defined Stereocenters	1 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CC1=C([C@@H](OC2=CC(O)=CC=C12)C3=CC=C(OCCN4CCCCC4)C=C3)C5=CC=C(O)C=C5

InChI

InChIKey=DUYNJNWVGIWJRI-LJAQVGFWSA-N

InChI=1S/C29H31NO4/c1-20-26-14-11-24(32)19-27(26)34-29(28(20)21-5-9-23(31)10-6-21)22-7-12-25(13-8-22)33-18-17-30-15-3-2-4-16-30/h5-14,19,29,31-32H,2-4,15-18H2,1H3/t29-/m0/s1

HIDE SMILES / InChI

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/11850228
Curator's Comment: description was created based on several sources, including: https://www.ncbi.nlm.nih.gov/pubmed/10418981 | http://en.pharmacodia.com/web/drug/1_2035.html | http://adisinsight.springer.com/drugs/800013630

Acolbifene, the active metabolite of EM-800, was identified as a pure antagonist that acts on both activation domains of the ERs. It is in Phase III clinical trials for the prevention of breast cancer and vasomotor symptoms (Hot flush) in postmenopausal women. Most commonly reported adverse events included irregular menses, leg/muscle cramps, diarrhea, and hot flashes. No serious adverse events were reported.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
UDP-glucuronosyltransferase 1-1 15 Target ID: CHEMBL1287617 Sources: https://www.ncbi.nlm.nih.gov/pubmed/11179460	Substrate 661
UDP-glucuronosyltransferase 1-3 6 Target ID: CHEMBL3542435 Sources: https://www.ncbi.nlm.nih.gov/pubmed/11179460	Substrate 661
UDP-glucuronosyltransferase 1-9 11 Target ID: CHEMBL1743319 Sources: https://www.ncbi.nlm.nih.gov/pubmed/11179460	Substrate 661
Estrogen receptor 72 Target ID: CHEMBL2093866 Sources: https://www.ncbi.nlm.nih.gov/pubmed/10418981	Antagonist 2849	0.52 nM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Breast cancer 432 Sources: https://www.ncbi.nlm.nih.gov/pubmed/26391916 http://en.pharmacodia.com/web/drug/1_2035.html	Primary		Phase III 665	Unknown Approved Use Unknown
Hot flushes 4 Sources: https://clinicaltrials.gov/ct2/show/NCT01452373	Palliative		Phase III 665	Unknown Approved Use Unknown

Overview

CYP3A4	CYP2C9	CYP2D6	hERG

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
SULT2A1 5	UGT1A3 470 UGT1A7 249 UGT1A10 331 UGT1A8 323 UGT2B4 278 UGT2B7 456 UGT1A9 423 UGT1A1 479 UGT1A4 399 UGT2B15 236 UGT1A6 343 UGT2B17 237

Drug as perpetrator

Target	Modality	Activity	Metabolite	Clinical evidence
SULT2A1 9	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/30918069/	yes [IC50 7 uM]

Drug as victim

Target	Modality	Activity
UGT1A7 249	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/11179460/	likely
UGT1A3 470	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/11179460/	major [Km 19 uM]
UGT1A1 479	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/11179460/	major [Km 63 uM]
UGT1A9 423	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/11179460/	major [Km 64 uM]
UGT1A8 323	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/11179460/	major
UGT1A10 331	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/11179460/	no
UGT1A4 399	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/11179460/	no
UGT1A6 343	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/11179460/	no
UGT2B15 236	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/11179460/	no
UGT2B17 237	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/11179460/	no
UGT2B4 278	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/11179460/	no
UGT2B7 456	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/11179460/	no

Sourcing

Vendor/Aggregator	ID	URL
Compound Cloud	155435
Compound Cloud	155436
eMolecules	260193583	https://orderbb.emolecules.com/search/#?query=260193583
eMolecules	85163536	https://orderbb.emolecules.com/search/#?query=85163536
Hairui	ACJB003	http://www.hairuichem.com/en/product/search.do?q=ACJB003
Lan Pharmatech	LQT-B02702
Lan Pharmatech	LQT-B02703
mcule	MCULE-1919792695	https://mcule.com/MCULE-1919792695/
mcule	MCULE-5402471704	https://mcule.com/MCULE-5402471704/
MolPort	MolPort-046-426-364	https://www.molport.com/shop/molecule-link/MolPort-046-426-364
MuseChem	R045581	https://www.musechem.com/product/R045581.html

PubMed

Title	Date	PubMed
Glucuronidation of the nonsteroidal antiestrogen EM-652 (SCH 57068), by human and monkey steroid conjugating UDP-glucuronosyltransferase enzymes.	2001-03	11179460
EM-652 (SCH 57068), a third generation SERM acting as pure antiestrogen in the mammary gland and endometrium.	1999-07-27	10418981
Blockade of the stimulatory effect of estrogens, OH-tamoxifen, OH-toremifene, droloxifene, and raloxifene on alkaline phosphatase activity by the antiestrogen EM-800 in human endometrial adenocarcinoma Ishikawa cells.	1997-08-15	9270018

Patents

Sample Use Guides

In Vivo Use Guide

20 mg daily for 6-8 months

Route of Administration: Oral

In Vitro Use Guide

As measured by competition studies in human breast cancer tissue, the anity of EM-652 (Ki=0.047 nM, RBA=291, relative to 17b-estradiol set at 100) studied in the presence of ethanol was 2.9 higher than that of estradiol itself (RBA=6.62).

Name

Type

Language

SCH-57068

Preferred Name

English

ACOLBIFENE

Official Name

English

2H-1-BENZOPYRAN-7-OL, 3-(4-HYDROXYPHENYL)-4-METHYL-2-(4-(2-(1-PIPERIDINYL)ETHOXY)PHENYL)-, (2S)-

Systematic Name

English

acolbifene [INN]

Common Name

English

2S)-3-(4-HYDROXYPHENYL)-4-METHYL-2-(4-(2-PIPERIDIN-1-YL-ETHOXY)PHENYL)-2H-CHROMEN-7-OL

Common Name

English

SCH57068

Code

English

Classification Tree Code System Code

NCI_THESAURUS

C1821