ORMELOXIFENE HYDROCHLORIDE

Possibly Marketed Outside US

Details

Stereochemistry	RACEMIC
Molecular Formula	C30H35NO3.ClH
Molecular Weight	494.065
Optical Activity	( + / - )
Defined Stereocenters	2 / 2
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

SMILES

Cl.COC1=CC2=C(C=C1)[C@H]([C@H](C3=CC=CC=C3)C(C)(C)O2)C4=CC=C(OCCN5CCCC5)C=C4

InChI

InChIKey=ZRGUGBSQWQXLHB-XZVFQGBBSA-N

InChI=1S/C30H35NO3.ClH/c1-30(2)29(23-9-5-4-6-10-23)28(26-16-15-25(32-3)21-27(26)34-30)22-11-13-24(14-12-22)33-20-19-31-17-7-8-18-31;/h4-6,9-16,21,28-29H,7-8,17-20H2,1-3H3;1H/t28-,29+;/m1./s1

HIDE SMILES / InChI

Molecular Formula	ClH
Molecular Weight	36.461
Charge	0
Count	MOL RATIO 1 MOL RATIO (average)

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Molecular Formula	C30H35NO3
Molecular Weight	457.6038
Charge	0
Count	MOL RATIO 1 MOL RATIO (average)

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	2 / 2
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description

Levormeloxifene (INN) is an experimental selective estrogen receptor modulator (SERM) that was being developed as an alternative to estrogen replacement therapy for the treatment and prevention of postmenopausal bone loss. Levormeloxifene is the levorotatory enantiomer of non-hormonal, non-steroidal oral contraceptive -- ormeloxifene (trade names Novex-DS, Centron, and Sevista). The development of Levormeloxifene was stopped because of a high incidence of gynecologic adverse events during clinical trials.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Estrogen receptor 75	Modulator 828
Estrogen receptor 75	Partial Agonist 290		13.0 nM [IC50]

Conditions

Condition	Modality	Highest Phase	Product
Ovarian cancer 157	Primary	Preclinical	Unknown
Dysfunctional uterine bleeding 7	Primary	Approved 8,429	SEVISTA
Pregnancy 65	Preventing	Approved 8,429	SEVISTA
Postmenopausal bone loss 8	Primary	Phase II 1,132	Unknown

C_max

Value	Dose	Analyte	Population
5.6 ng/mL	2.5 mg single, oral	LEVORMELOXIFENE plasma	Homo sapiens
27 ng/mL	10 mg single, oral	LEVORMELOXIFENE plasma	Homo sapiens
128 ng/mL	30 mg single, oral	LEVORMELOXIFENE plasma	Homo sapiens
443 ng/mL	80 mg single, oral	LEVORMELOXIFENE plasma	Homo sapiens
1115 ng/mL	160 mg single, oral	LEVORMELOXIFENE plasma	Homo sapiens
2737 ng/mL	320 mg single, oral	LEVORMELOXIFENE plasma	Homo sapiens
71 ng/mL	20 mg 1 times / day multiple, oral	LEVORMELOXIFENE plasma	Homo sapiens
254 ng/mL	20 mg 1 times / day multiple, oral	LEVORMELOXIFENE plasma	Homo sapiens
387 ng/mL	80 mg 1 times / day multiple, oral	LEVORMELOXIFENE plasma	Homo sapiens
1081 ng/mL	80 mg 1 times / day multiple, oral	LEVORMELOXIFENE plasma	Homo sapiens
769 ng/mL	160 mg 1 times / day multiple, oral	LEVORMELOXIFENE plasma	Homo sapiens
2031 ng/mL	160 mg 1 times / day multiple, oral	LEVORMELOXIFENE plasma	Homo sapiens
182 ng/mL	40 mg 1 times / day multiple, oral	LEVORMELOXIFENE plasma	Homo sapiens
477 ng/mL	40 mg 1 times / day multiple, oral	LEVORMELOXIFENE plasma	Homo sapiens
377 ng/mL	80 mg 1 times / day multiple, oral	LEVORMELOXIFENE plasma	Homo sapiens
879 ng/mL	80 mg 1 times / day multiple, oral	LEVORMELOXIFENE plasma	Homo sapiens
147 ng/mL	40 mg single, oral	LEVORMELOXIFENE plasma	Homo sapiens
141 ng/mL	40 mg single, oral	LEVORMELOXIFENE plasma	Homo sapiens

AUC

Value	Dose	Analyte	Population
3.2 μg × h/mL	10 mg single, oral	LEVORMELOXIFENE plasma	Homo sapiens
10 μg × h/mL	30 mg single, oral	LEVORMELOXIFENE plasma	Homo sapiens
26 μg × h/mL	80 mg single, oral	LEVORMELOXIFENE plasma	Homo sapiens
64 μg × h/mL	160 mg single, oral	LEVORMELOXIFENE plasma	Homo sapiens
129 μg × h/mL	320 mg single, oral	LEVORMELOXIFENE plasma	Homo sapiens
1 μg × h/mL	20 mg 1 times / day multiple, oral	LEVORMELOXIFENE plasma	Homo sapiens
4.7 μg × h/mL	20 mg 1 times / day multiple, oral	LEVORMELOXIFENE plasma	Homo sapiens
4.8 μg × h/mL	80 mg 1 times / day multiple, oral	LEVORMELOXIFENE plasma	Homo sapiens
19.8 μg × h/mL	80 mg 1 times / day multiple, oral	LEVORMELOXIFENE plasma	Homo sapiens
9 μg × h/mL	160 mg 1 times / day multiple, oral	LEVORMELOXIFENE plasma	Homo sapiens
33.4 μg × h/mL	160 mg 1 times / day multiple, oral	LEVORMELOXIFENE plasma	Homo sapiens
2.4 μg × h/mL	40 mg 1 times / day multiple, oral	LEVORMELOXIFENE plasma	Homo sapiens
8.5 μg × h/mL	40 mg 1 times / day multiple, oral	LEVORMELOXIFENE plasma	Homo sapiens
4.9 μg × h/mL	80 mg 1 times / day multiple, oral	LEVORMELOXIFENE plasma	Homo sapiens
15.2 μg × h/mL	80 mg 1 times / day multiple, oral	LEVORMELOXIFENE plasma	Homo sapiens
9771 ng × h/mL	40 mg single, oral	LEVORMELOXIFENE plasma	Homo sapiens
12181 ng × h/mL	40 mg single, oral	LEVORMELOXIFENE plasma	Homo sapiens

T_1/2

Value	Dose	Analyte	Population
8.4 h	10 mg single, oral	LEVORMELOXIFENE plasma	Homo sapiens
6.9 h	30 mg single, oral	LEVORMELOXIFENE plasma	Homo sapiens
5.8 h	80 mg single, oral	LEVORMELOXIFENE plasma	Homo sapiens
5.4 h	160 mg single, oral	LEVORMELOXIFENE plasma	Homo sapiens
6 h	320 mg single, oral	LEVORMELOXIFENE plasma	Homo sapiens
5.9 h	20 mg 1 times / day multiple, oral	LEVORMELOXIFENE plasma	Homo sapiens
5.4 h	80 mg 1 times / day multiple, oral	LEVORMELOXIFENE plasma	Homo sapiens
5.5 h	160 mg 1 times / day multiple, oral	LEVORMELOXIFENE plasma	Homo sapiens
5.1 h	40 mg 1 times / day multiple, oral	LEVORMELOXIFENE plasma	Homo sapiens
4.8 h	80 mg 1 times / day multiple, oral	LEVORMELOXIFENE plasma	Homo sapiens
126 h	40 mg single, oral	LEVORMELOXIFENE plasma	Homo sapiens
151 h	40 mg single, oral	LEVORMELOXIFENE plasma	Homo sapiens

F_unbound

Value	Dose	Co-administered	Analyte	Population
0.1%			LEVORMELOXIFENE plasma	Homo sapiens

Doses

Show entries

Dose	Population	Adverse events
20 mg 1 times / day steady-state, oral Highest studied dose	unhealthy, ADULT	Other AEs: Edema, Endometrial polyps...
1.25 mg 1 times / day steady-state, oral Studied dose	unhealthy, ADULT	Other AEs: leukorrhea, Endometrial disorder...
1.25 mg 1 times / day steady-state, oral Studied dose	unhealthy, ADULT	Other AEs: Edema, Endometrial polyps...
10 mg 1 times / day steady-state, oral Studied dose	unhealthy, ADULT	Other AEs: Hot flushes, Breast pain...
10 mg 1 times / day steady-state, oral Studied dose	unhealthy, ADULT	Other AEs: Edema, Endometrial polyps...

Showing 1 to 5 of 6 entries

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AEs

Show entries

AE	Significance	Dose	Population
Endometrial polyps	6%	20 mg 1 times / day steady-state, oral Highest studied dose	unhealthy, ADULT
Edema	75%	20 mg 1 times / day steady-state, oral Highest studied dose	unhealthy, ADULT
hot flushes	10%	1.25 mg 1 times / day steady-state, oral Studied dose	unhealthy, ADULT
enlarged uterus	17%	1.25 mg 1 times / day steady-state, oral Studied dose	unhealthy, ADULT
lower abdominal pain	17%	1.25 mg 1 times / day steady-state, oral Studied dose	unhealthy, ADULT

Showing 1 to 5 of 23 entries

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PubMed

Show entries

Title	Date	PubMed
Modulation of estrogen receptor transactivation and estrogen-induced gene expression by ormeloxifene-a triphenylethylene derivative.	2006 Nov	16965798
Expression of oestrogen receptors alpha and beta during the period of uterine receptivity in rat: effect of ormeloxifene, a selective oestrogen receptor modulator.	2007 Jan	17280556
Role of centchroman in regression of mastalgia and fibroadenoma.	2007 Jun	17431715
Modulation of AP-1 mediated estrogenic response by ormeloxifene in rat uterus.	2007 May	17553677
Expression of estrogen receptor co-regulators SRC-1, RIP140 and NCoR and their interaction with estrogen receptor in rat uterus, under the influence of ormeloxifene.	2009 Aug	19460436

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Patents

Sample Use Guides

In Vivo Use Guide

Dosage Oral Dysfunctional uterine bleeding Adult: 60 mg twice a week for the 1st 12 weeks and then 60 mg once a week for up to next 12 weeks. Oral Contraception Adult: Take 1 tablet (30 mg) twice a week for the 1st 12 weeks then 1 tablet (30 mg) once a week from 13th weeks onwards. Take 1st tablet on the 1st day of menstrual cycle. Follow dose irrespective of menstrual periods.

Route of Administration: Oral

In Vitro Use Guide

Ormeloxifene (10(-6) and 10(-8)M) significantly inhibited osteoclastogenesis (P<0.001 versus vehicle control) as evidenced by lower number of TRAP-positive osteoclasts in bone marrow cultures and caused apoptosis of osteoclasts from adult Balb/c mice.

Substance Class	Chemical
Record UNII	GL3LAI70F3
Record Status	`Validated (UNII)`
Record Version

Show entries

Name

Type

Language

ORMELOXIFENE HYDROCHLORIDE

Common Name

English

CENTCHROMAN HYDROCHLORIDE

Common Name

English

6720 CDRI

Code

English

PYRROLIDINE, 1-(2-(4-((3R,4R)-3,4-DIHYDRO-7-METHOXY-2,2-DIMETHYL-3-PHENYL-2H-1-BENZOPYRAN-4-YL)PHENOXY)ETHYL)-, HYDROCHLORIDE (1:1), REL-

Systematic Name

English

CENTCHROMAN HYDROCHLORIDE [MI]

Common Name

English

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Code System

Code

Type

Description

CAS

51023-56-4

PRIMARY

FDA UNII

GL3LAI70F3

PRIMARY

MERCK INDEX

m3242

PRIMARY

Merck Index

SMS_ID

300000041211

PRIMARY

EPA CompTox

DTXSID40965301

PRIMARY

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Related Record

Type

Details


					44AXY5VE90

ORMELOXIFENE

PARENT -> SALT/SOLVATE

Amount:

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SMILES

InChI

Originator

Approval Year

Targets

Conditions

Cmax

AUC

T1/2

Funbound

Doses

AEs

PubMed

Patents

Sample Use Guides

C_max

T_1/2

F_unbound