TANAPROGET

Details

Stereochemistry	ACHIRAL
Molecular Formula	C16H15N3OS
Molecular Weight	297.375
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CN1C(=CC=C1C2=CC3=C(NC(=S)OC3(C)C)C=C2)C#N

InChI

InChIKey=PYVFWTPEBMRKSR-UHFFFAOYSA-N

InChI=1S/C16H15N3OS/c1-16(2)12-8-10(4-6-13(12)18-15(21)20-16)14-7-5-11(9-17)19(14)3/h4-8H,1-3H3,(H,18,21)

HIDE SMILES / InChI

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/15937332
Curator's Comment: Description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/16418212 | http://adisinsight.springer.com/drugs/800017577 | https://www.ncbi.nlm.nih.gov/pubmed/20355713 | https://www.ncbi.nlm.nih.gov/pubmed/20496889 | https://www.ncbi.nlm.nih.gov/pubmed/21204318

Tanaproget (WAY-166989) is a nonsteroidal progesterone receptor agonist. It has been in Phase-II clinical trials as an oral contraceptive. The compound demonstrated a positive preclinical pharmacological profile in the treatment of endometriosis. The level of progesterone receptors in breast tumours can be used to guide the selection of endocrine therapies for breast cancer patients. Radiolabeled analogues of tanaproget have diagnostic potential as PET imaging agents for breast cancer.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Progesterone receptor 61 Target ID: CHEMBL208 Sources: https://www.ncbi.nlm.nih.gov/pubmed/16078826 \| https://www.ncbi.nlm.nih.gov/pubmed/15937332	Agonist 2678		1.7 nM [IC50]

Conditions

Condition	Modality	Highest Phase	Product
Pregnancy 65 Sources: http://adisinsight.springer.com/drugs/800017577	Preventing	Phase II 1132	Unknown Approved Use Unknown
Endometriosis 32 Sources: https://www.ncbi.nlm.nih.gov/pubmed/16418212	Primary	Preclinical	Unknown Approved Use Unknown
Breast cancer 434 Sources: https://www.ncbi.nlm.nih.gov/pubmed/20355713 https://www.ncbi.nlm.nih.gov/pubmed/20496889 https://www.ncbi.nlm.nih.gov/pubmed/21204318	Diagnostic	Preclinical	Unknown Approved Use Unknown

C_max

Value	Dose	Analyte	Population
0.3 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/17046384	0.1 mg single, oral dose: 0.1 mg route of administration: Oral experiment type: SINGLE co-administered:	TANAPROGET plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: FASTED
12.63 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/17046384	7 mg single, oral dose: 7 mg route of administration: Oral experiment type: SINGLE co-administered:	TANAPROGET plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: HIGH-FAT
10.04 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/17046384	7 mg single, oral dose: 7 mg route of administration: Oral experiment type: SINGLE co-administered:	TANAPROGET plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: FASTED
1.99 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/17046384	1 mg single, oral dose: 1 mg route of administration: Oral experiment type: SINGLE co-administered:	TANAPROGET plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: FASTED
16.21 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/17046384	15 mg single, oral dose: 15 mg route of administration: Oral experiment type: SINGLE co-administered:	TANAPROGET plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: UNKNOWN
0.64 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/17046384	0.3 mg single, oral dose: 0.3 mg route of administration: Oral experiment type: SINGLE co-administered:	TANAPROGET plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: FASTED
3.93 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/17046384	3 mg single, oral dose: 3 mg route of administration: Oral experiment type: SINGLE co-administered:	TANAPROGET plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: FASTED

AUC

Value	Dose	Analyte	Population
1.58 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/17046384	0.1 mg single, oral dose: 0.1 mg route of administration: Oral experiment type: SINGLE co-administered:	TANAPROGET plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: FASTED
112.2 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/17046384	7 mg single, oral dose: 7 mg route of administration: Oral experiment type: SINGLE co-administered:	TANAPROGET plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: HIGH-FAT
134.9 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/17046384	7 mg single, oral dose: 7 mg route of administration: Oral experiment type: SINGLE co-administered:	TANAPROGET plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: FASTED
15.9 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/17046384	1 mg single, oral dose: 1 mg route of administration: Oral experiment type: SINGLE co-administered:	TANAPROGET plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: FASTED
152.9 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/17046384	15 mg single, oral dose: 15 mg route of administration: Oral experiment type: SINGLE co-administered:	TANAPROGET plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: UNKNOWN
3.48 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/17046384	0.3 mg single, oral dose: 0.3 mg route of administration: Oral experiment type: SINGLE co-administered:	TANAPROGET plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: FASTED
45.5 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/17046384	3 mg single, oral dose: 3 mg route of administration: Oral experiment type: SINGLE co-administered:	TANAPROGET plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: FASTED

T_1/2

Value	Dose	Analyte	Population
4.6 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/17046384	0.1 mg single, oral dose: 0.1 mg route of administration: Oral experiment type: SINGLE co-administered:	TANAPROGET plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: FASTED
20.4 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/17046384	7 mg single, oral dose: 7 mg route of administration: Oral experiment type: SINGLE co-administered:	TANAPROGET plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: HIGH-FAT
30.2 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/17046384	7 mg single, oral dose: 7 mg route of administration: Oral experiment type: SINGLE co-administered:	TANAPROGET plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: FASTED
11.7 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/17046384	1 mg single, oral dose: 1 mg route of administration: Oral experiment type: SINGLE co-administered:	TANAPROGET plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: FASTED
16.5 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/17046384	15 mg single, oral dose: 15 mg route of administration: Oral experiment type: SINGLE co-administered:	TANAPROGET plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: UNKNOWN
4.3 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/17046384	0.3 mg single, oral dose: 0.3 mg route of administration: Oral experiment type: SINGLE co-administered:	TANAPROGET plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: FASTED
18 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/17046384	3 mg single, oral dose: 3 mg route of administration: Oral experiment type: SINGLE co-administered:	TANAPROGET plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: FASTED

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inducer 781 substrate 1737

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYPs 22	UGT2B7 389 UGT1A9 380

Drug as perpetrator

Target	Modality	Activity	Metabolite	Clinical evidence
CYP3A4 1925	inducer 1573 Sources: https://pubmed.ncbi.nlm.nih.gov/15937332/	no
CYPs 28	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/15937332/	no

Drug as victim

Target	Modality	Activity
UGT1A9 380	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/16698893/	major
UGT2B7 389	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/16698893/	major
CYP3A4 1737	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/15937332/	no

Sourcing

Vendor/Aggregator	ID	URL
1PlusChem LLC	1P0030QO	https://www.1pchem.com/search?query=1P0030QO
ApexBio Technology	A3857	https://www.apexbt.com/catalogsearch/result/?q=A3857
BLD Pharm	BD630626	http://www.bldpharm.com/search/Search.html?keyword=BD630626
Debye Scientific	DA-38867	https://www.debyesci.com/index.php?id=product&ext[cno]=DA-38867
Lab Network	LN01342651	https://labnetwork.com/frontend-app/p/#!/moleculedetails/LN01342651
MedChem Express	HY-15606	https://www.medchemexpress.com/search.html?q=HY-15606&ft=&fa=&fp=
MolPort	MolPort-006-169-960	https://www.molport.com/shop/molecule-link/MolPort-006-169-960
MuseChem	I003069	https://www.musechem.com/product/I003069.html
eMolecules	50282672	https://orderbb.emolecules.com/search/#?query=50282672
mcule	MCULE-9916037399	https://mcule.com/MCULE-9916037399/

PubMed

Title	Date	PubMed
Synthesis and structure-activity relationship of novel 6-aryl-1,4-dihydrobenzo[d][1,3]oxazine-2-thiones as progesterone receptor modulators leading to the potent and selective nonsteroidal progesterone receptor agonist tanaproget.	2005 Aug 11	16078826
Molecular and pharmacological properties of a potent and selective novel nonsteroidal progesterone receptor agonist tanaproget.	2005 Aug 5	15937332
Gateways to clinical trials.	2005 Sep	16258596
Down-regulation of endometrial matrix metalloproteinase-3 and -7 expression in vitro and therapeutic regression of experimental endometriosis in vivo by a novel nonsteroidal progesterone receptor agonist, tanaproget.	2006 Apr	16418212
NMR characterization of an S-linked glucuronide metabolite of the potent, novel, nonsteroidal progesterone agonist tanaproget.	2006 Aug	16698893
Docking and three-dimensional quantitative structure-activity relationship (3D QSAR) analyses of nonsteroidal progesterone receptor ligands.	2006 Jul 13	16821785
Pharmacokinetics and safety of tanaproget, a nonsteroidal progesterone receptor agonist, in healthy women.	2006 Nov	17046384
Development of a mouse model of mammary gland versus uterus tissue selectivity using estrogen- and progesterone-regulated gene markers.	2006 Sep	16920353
A new generation of progesterone receptor modulators.	2008 Aug	18472121
Design, synthesis, and SAR of new pyrrole-oxindole progesterone receptor modulators leading to 5-(7-fluoro-3,3-dimethyl-2-oxo-2,3-dihydro-1H-indol-5-yl)-1-methyl-1H-pyrrole-2-carbonitrile (WAY-255348).	2008 Mar 27	18318463
Imaging progesterone receptor in breast tumors: synthesis and receptor binding affinity of fluoroalkyl-substituted analogues of tanaproget.	2010 Apr 22	20355713
Development of [F-18]fluorine-substituted Tanaproget as a progesterone receptor imaging agent for positron emission tomography.	2010 Jun 16	20496889

Patents

Sample Use Guides

In Vivo Use Guide

A randomized, double-blind, placebo-controlled, sequential-group study of ascending single doses of tanaproget was conducted in healthy, 25- to 45-year-old women on cycle days 8 to 12. Eight subjects (six active, two placebo) per cohort received a dose of 0.1, 0.3, 1, 3, 7 (+/-high-fat meal) or 15 mg.

Route of Administration: Oral

In Vitro Use Guide

0.1 and 1 nM tanaproget effectively down-regulated matrix metalloproteinase 3 and 7 expression in vitro in endometrial stromal cells

Name

Type

Language

TANAPROGET

Official Name

English

tanaproget [INN]

Common Name

English

5-(4,4-Dimethyl-2-thioxo-1,4-dihydro-2H-3,1-benzoxazin-6-yl)-1-methyl-1H-pyrrole-2-carbonitrile

Systematic Name

English

TANAPROGET [USAN]

Common Name

English

NSP-989

Code

English

Classification Tree Code System Code

NCI_THESAURUS

C776