ENOBOSARM

Investigational

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C19H14F3N3O3
Molecular Weight	389.328
Optical Activity	UNSPECIFIED
Defined Stereocenters	1 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

C[C@](O)(COC1=CC=C(C=C1)C#N)C(=O)NC2=CC=C(C#N)C(=C2)C(F)(F)F

InChI

InChIKey=JNGVJMBLXIUVRD-SFHVURJKSA-N

InChI=1S/C19H14F3N3O3/c1-18(27,11-28-15-6-2-12(9-23)3-7-15)17(26)25-14-5-4-13(10-24)16(8-14)19(20,21)22/h2-8,27H,11H2,1H3,(H,25,26)/t18-/m0/s1

HIDE SMILES / InChI

Molecular Formula	C19H14F3N3O3
Molecular Weight	389.328
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	1 / 1
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/19852734https://www.ncbi.nlm.nih.gov/pubmed/24490605
Curator's Comment: Description was created based on several sources, including

Enobosarm, also known as ostarine, is an investigational selective androgen receptor modulator (SARM) from GTX, Inc for treatment of conditions such as muscle wasting and osteoporosis. Enobosarm has been tested in Phase I, II and III trials with promising results in terms of improving lean body mass and measurements of physical function and power. Enobosarm has received fast track designation by the US FDA. Enobosarm is a selective androgen receptor modulator (SARM) with Ki of 3.8 nM, and is tissue-selective for anabolic organs. It is in Phase II for Breast cancer and Stress incontinence and discontinued for Cachexia and Muscular atrophy.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Androgen Receptor 167 Target ID: CHEMBL1871 Sources: https://www.ncbi.nlm.nih.gov/pubmed/15987833	Modulator 822		3.8 nM [Ki]
Androgen Receptor 167 Target ID: CHEMBL1871 Sources: https://www.ncbi.nlm.nih.gov/pubmed/26393303	Modulator 822		3.8 nM [Ki]

Conditions

Condition	Modality	Highest Phase	Product
Breast cancer 431 Sources: https://clinicaltrials.gov/ct2/show/NCT01616758	Primary	Phase II 1144	Unknown Approved Use Unknown
Muscle wasting in non-small cell lung cancer 1 Sources: https://clinicaltrials.gov/ct2/show/NCT01355484	Primary	Phase III 663	Unknown Approved Use Unknown
Cachexia related to cancer 1 Sources: https://clinicaltrials.gov/ct2/show/NCT00467844	Primary	Phase II 1144	Unknown Approved Use Unknown
Muscle wasting in non-small cell lung cancer 1 Sources: https://clinicaltrials.gov/ct2/show/NCT01355497	Primary	Phase III 663	Unknown Approved Use Unknown
Metastatic breast cancer 6 Sources: https://clinicaltrials.gov/ct2/show/NCT01616758	Primary	Phase II 1144	Unknown Approved Use Unknown

C_max

Value	Dose	Co-administered	Analyte	Population
57.6 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27105861	3 mg 1 times / day single, oral dose: 3 mg route of administration: Oral experiment type: SINGLE co-administered:		ENOBOSARM plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
779.5 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27105861	3 mg 1 times / day single, oral dose: 3 mg route of administration: Oral experiment type: SINGLE co-administered:		ENOBOSARM plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
22 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27105861	3 mg 1 times / day single, oral dose: 3 mg route of administration: Oral experiment type: SINGLE co-administered:		ENOBOSARM plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

Doses

Dose	Population	Adverse events
3 mg 1 times / day multiple, oral Highest studied dose Dose: 3 mg, 1 times / day Route: oral Route: multiple Dose: 3 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/22031847 Page: p.155	healthy, ADULT n = 24 Health Status: healthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 24 Sources: https://pubmed.ncbi.nlm.nih.gov/22031847 Page: p.155	Disc. AE: ALT increased... AEs leading to discontinuation/dose reduction: ALT increased (4.2%) Sources: https://pubmed.ncbi.nlm.nih.gov/22031847 Page: p.155
3 mg 1 times / day multiple, oral Highest studied dose Dose: 3 mg, 1 times / day Route: oral Route: multiple Dose: 3 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/23499390 Page: p.7	unhealthy, ADULT n = 54 Health Status: unhealthy Condition: cancer Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 54 Sources: https://pubmed.ncbi.nlm.nih.gov/23499390 Page: p.7	Sources: https://pubmed.ncbi.nlm.nih.gov/23499390 Page: p.7

AEs

AE	Significance	Dose	Population
ALT increased	4.2% Disc. AE	3 mg 1 times / day multiple, oral Highest studied dose Dose: 3 mg, 1 times / day Route: oral Route: multiple Dose: 3 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/22031847 Page: p.155	healthy, ADULT n = 24 Health Status: healthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 24 Sources: https://pubmed.ncbi.nlm.nih.gov/22031847 Page: p.155

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inhibitor 1579 substrate 1709	inhibitor 1752 substrate 1010	inhibitor 1837 substrate 1193

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP1A2 1509 CYP2C19 1463 BCRP 691 OATP1B1 781	UGT1A8 283 CYP2C19 985 CYP1A2 1032 UGT2B7 389 UGT1A4 347 UGT1A6 307 UGT2B15 203 UGT1A10 290 UGT1A1 418 P-gp 1527

Drug as perpetrator

Target	Modality	Activity	Clinical evidence
CYP1A2 1673	inhibitor 3240 Sources: https://pubmed.ncbi.nlm.nih.gov/27105861/	no [IC50 >10 uM]
CYP2D6 1875	inhibitor 3240 Sources: https://pubmed.ncbi.nlm.nih.gov/27105861/	no [IC50 >10 uM]
CYP3A4 1909	inhibitor 3240 Sources: https://pubmed.ncbi.nlm.nih.gov/27105861/	no [IC50 >10 uM]
OATP1B1 796	inhibitor 3240 Sources: https://pubmed.ncbi.nlm.nih.gov/34164937/	no
BCRP 765	inhibitor 3240 Sources: https://pubmed.ncbi.nlm.nih.gov/27105861/	yes [IC50 1.31 uM]	yes (co-administration study) Comment: Increased rosubastatin Cmax and AUCinf by 29% and 18%. Sources: https://pubmed.ncbi.nlm.nih.gov/27105861/
CYP2C9 1803	inhibitor 3240 Sources: https://pubmed.ncbi.nlm.nih.gov/27105861/	yes [IC50 1.6 uM]	yes (co-administration study) Comment: Decreased celecoxib Cmax and AUCinf by 13% and 10%. Sources: https://pubmed.ncbi.nlm.nih.gov/27105861/
CYP2C19 1537	inhibitor 3240 Sources: https://pubmed.ncbi.nlm.nih.gov/27105861/	yess [IC50 0.7 uM]

Drug as victim

Target	Modality	Activity	Clinical evidence
CYP3A4 1709	substrate 3326 Sources: https://pubmed.ncbi.nlm.nih.gov/27105861/	major	yes (co-administration study) Comment: Rifampicin decreased Cmax and AUCinf by 23% and 43%. Sources: https://pubmed.ncbi.nlm.nih.gov/27105861/
UGT1A1 418	substrate 3326 Sources: https://pubmed.ncbi.nlm.nih.gov/27105861/	major	yes (co-administration study) Comment: Probenecid increased AUCinf by 50% and decreased Cmax by 6.7%. Sources: https://pubmed.ncbi.nlm.nih.gov/27105861/
UGT2B7 389	substrate 3326 Sources: https://pubmed.ncbi.nlm.nih.gov/27105861/	major	yes (co-administration study) Comment: Probenecid increased AUCinf by 50% and decreased Cmax by 6.7%. Sources: https://pubmed.ncbi.nlm.nih.gov/27105861/
CYP2C19 985	substrate 3326 Sources: https://pubmed.ncbi.nlm.nih.gov/27105861/	minor
CYP2D6 1193	substrate 3326 Sources: https://pubmed.ncbi.nlm.nih.gov/27105861/	minor
UGT1A10 290	substrate 3326 Sources: https://pubmed.ncbi.nlm.nih.gov/27105861/	minor
UGT1A4 347	substrate 3326 Sources: https://pubmed.ncbi.nlm.nih.gov/27105861/	minor
UGT1A6 307	substrate 3326 Sources: https://pubmed.ncbi.nlm.nih.gov/27105861/	minor
UGT1A8 283	substrate 3326 Sources: https://pubmed.ncbi.nlm.nih.gov/27105861/	minor
UGT2B15 203	substrate 3326 Sources: https://pubmed.ncbi.nlm.nih.gov/27105861/	minor
CYP1A2 1032	substrate 3326 Sources: https://pubmed.ncbi.nlm.nih.gov/27105861/	no
CYP2C9 1010	substrate 3326 Sources: https://pubmed.ncbi.nlm.nih.gov/27105861/	no
P-gp 1527	substrate 3326 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1346987#sid=174007253	no

PubMed

Title	Date	PubMed
Nonsteroidal selective androgen receptor modulator Ostarine in cancer cachexia.	2009 Oct	19852734
Effects of enobosarm on muscle wasting and physical function in patients with cancer: a double-blind, randomised controlled phase 2 trial.	2013 Apr	23499390
Absorption, distribution, metabolism and excretion of the novel SARM GTx-024 [(S)-N-(4-cyano-3-(trifluoromethyl)phenyl)-3-(4-cyanophenoxy)-2-hydroxy-2-methylpropanamide] in rats.	2013 Nov	24074268
Enobosarm (GTx-024) Modulates Adult Skeletal Muscle Mass Independently of the Androgen Receptor in the Satellite Cell Lineage.	2015 Dec	26393303

Patents

Sample Use Guides

In Vivo Use Guide

1 or 3 mg Gtx-024 once daily for 16 weeks in patients with cancer induced muscle loss, (cancer cachexia)

Route of Administration: Oral

In Vitro Use Guide

Enobosarm at the concentration of 10 nM modulates the transcriptional activity of AR in CV-1 cells cotransfected with a human AR expression vector, a luciferase reporter vector, and a control β-galactosidase vector, with 94%-100% relative activity of the transcriptional activation observed for 1 nM DHT.

Substance Class	Chemical Created by `admin` on `Thu Jul 06 22:22:28 UTC 2023` Edited by `admin` on `Thu Jul 06 22:22:28 UTC 2023`
Record UNII	O3571H3R8N
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

ENOBOSARM

Official Name

English

PROPANAMIDE, 3-(4-CYANOPHENOXY)-N-(4-CYANO-3-(TRIFLUOROMETHYL)PHENYL)-2-HYDROXY-2-METHYL-, (2S)-

Systematic Name

English

ENOBOSARM [USAN]

Common Name

English

GTX-024

Code

English

enobosarm [INN]

Common Name

English

Enobosarm [WHO-DD]

Common Name

English

OSTARINE

Brand Name

English

MK-2866

Code

English

Classification Tree Code System Code

DSLD

3985 (Number of products:13)