Norethindrone

Summary

Norethindrone (CHEMBL1162) is an approved small-molecule synthetic oral contraceptive (ATC G03DC02) targeting PGR; indicated across 13 conditions including physiological sexual disorder and endometriosis.

At a glance

• Status: Approved (max clinical phase 4)
• Modality: Small molecule
• ATC class: G03DC02 (+1 more)
• Targets: 1 (PGR)
• Indications: 13 conditions
• Clinical trials: 45
• Chemistry: 298.4 Da · C20H26O2

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL1162
Name	Norethindrone
Type	Small molecule
Max phase	4
FDA approved	yes
PubChem CID	6230
ChEBI	CHEBI:7627
ATC	G03DC02, G03AC01
Molecular formula	C20H26O2
Molecular weight	298.4
InChIKey	VIKNJXKGJWUCNN-XGXHKTLJSA-N

SMILES: C[C@]12CC[C@H]3[C@H]([C@@H]1CC[C@]2(C#C)O)CCC4=CC(=O)CC[C@H]34

IUPAC name: (8R,9S,10R,13S,14S,17R)-17-ethynyl-17-hydroxy-13-methyl-1,2,6,7,8,9,10,11,12,14,15,16-dodecahydrocyclopenta[a]phenanthren-3-one

ChEBI definition: A 17β-hydroxy steroid that is testosterone in which the hydrogen at position 17 is replaced by an ethynyl group and in which the methyl group attached to position 10 is replaced by hydrogen.

Pharmacological roles (ChEBI): synthetic oral contraceptive, progestin.

Also known as: Anovule, Activella, Calluna vulgaris, Calluna vulgaris whole, Camila, Combipatch, Errin, Femhrt, Gestest, Heather, Heather whole, Incassia

Patent coverage: 55,032 distinct patent families (91,150 SureChEMBL compound mentions), from 1 matched compound structure(s). Mentions count patents naming the compound (not distinct inventions), so promiscuous / reference molecules inflate the mention figure — families are the dedup metric.

Targets

Targets

Primary targets (GtoPdb curated mechanism): the Cancer dependency column is the DepMap CRISPR fitness signal (% of screened cell lines dependent on the target).

Gene	Target	Action	pAffinity	Cancer dependency	UniProt
PGR	Progesterone receptor	Agonist	8.66	0.1%	P06401

Broader ChEMBL bioactivity targets: 9 (assay-derived). Sample: Alpha-2A adrenergic receptor, Glucocorticoid receptor, Estrogen receptor, Progesterone receptor, Estrogen receptor, Sodium-dependent serotonin transporter, Androgen receptor, Sex hormone-binding globulin, Bile salt export pump.

Bioactivity

ChEMBL activities: 18 potent at pChembl ≥ 5 of 22 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
PGR	9.4	Kd	0.4	nM	CHEMBL_ACT_686070
P06211	9.2	Kd	0.63	nM	CHEMBL_ACT_963211
PGR	8.73	Ki	1.87	nM	CHEMBL_ACT_700985
PGR	8.66	EC50	2.2	nM	CHEMBL_ACT_700983
PGR	8.49	IC50	3.2	nM	CHEMBL_ACT_667197
PGR	8.33	AC50	4.7	nM	CHEMBL_ACT_25222846
SHBG	7.97	Kd	10.72	nM	CHEMBL_ACT_2155707
P15207	7.82	Ki	15	nM	CHEMBL_ACT_7725109
P15207	7.66	IC50	22	nM	CHEMBL_ACT_7725108
P15207	7.35	AC50	45	nM	CHEMBL_ACT_25187312
NR3C1	7.09	AC50	82	nM	CHEMBL_ACT_25175625
P15207	6.92	IC50	120.2	nM	CHEMBL_ACT_1605631
NR3C1	6.71	Ki	197	nM	CHEMBL_ACT_7722970
ESR1	6.64	Ki	231	nM	CHEMBL_ACT_7722960
NR3C1	6.36	IC50	433	nM	CHEMBL_ACT_7722969
ESR1	6.09	IC50	808	nM	CHEMBL_ACT_7722959
SLC6A4	5.62	Ki	2411	nM	CHEMBL_ACT_7725097
SLC6A4	5.34	IC50	4537	nM	CHEMBL_ACT_7725096

Target pathways

Aggregated over 1 target gene(s): PGR.

Top Reactome pathways

7 total, by targets touching each:

Pathway	Targets	Genes
Nuclear signaling by ERBB4	1	PGR
HSP90 chaperone cycle for steroid hormone receptors (SHR) in the presence of ligand	1	PGR
Nuclear Receptor transcription pathway	1	PGR
SUMOylation of intracellular receptors	1	PGR
Estrogen-dependent gene expression	1	PGR
Developmental Lineage of Mammary Gland Luminal Epithelial Cells	1	PGR
Developmental Lineage of Mammary Gland Alveolar Cells	1	PGR

Dominant GO biological processes

GO term	Targets
ovulation from ovarian follicle	1
glandular epithelial cell maturation	1
regulation of DNA-templated transcription	1
regulation of transcription by RNA polymerase II	1
signal transduction	1
cell-cell signaling	1
positive regulation of gene expression	1
negative regulation of gene expression	1
nuclear receptor-mediated steroid hormone signaling pathway	1
paracrine signaling	1
positive regulation of transcription by RNA polymerase II	1
lung alveolus development	1
regulation of epithelial cell proliferation	1
progesterone receptor signaling pathway	1
maintenance of protein location in nucleus	1

Indications & clinical

Indications

13 indications (0 at ChEMBL trial phase 4). Phase below is the highest clinical-trial phase recorded for this drug against each disease — not the molecule’s overall approval status (that is in the Summary).

Indication	Trial phase	MONDO	EFO
physiological sexual disorder	3	MONDO:0002134	EFO:0004714
endometriosis	3	MONDO:0005133	EFO:0001065
ischemia reperfusion injury	2	MONDO:0005203	EFO:0002687
relapsing-remitting multiple sclerosis	2	MONDO:0005314	EFO:0003929
primary progressive multiple sclerosis	2	MONDO:0000451	EFO:0008520
secondary progressive multiple sclerosis	2	MONDO:0000450	EFO:0008522
neoplasm	1	MONDO:0005070	EFO:0000616
hepatitis C virus infection	1	MONDO:0005231	EFO:0003047

5 further indication records had no mapped disease name (EFO/MeSH-only) or were duplicates, and are omitted.

Clinical trials

Total trials: 45.

Phase distribution

Phase	Trials
PHASE3	14
PHASE1	11
PHASE4	8
PHASE2	6
Not specified	6

Top trials by phase / activity

NCT	Phase	Status	Title
NCT07293728	PHASE4	NOT_YET_RECRUITING	A Randomized Feasibility Trial Comparing Drospirenone and Norethindrone for Postpartum Hypertension Management in Preeclampsia
NCT00732693	PHASE4	COMPLETED	Evaluation of Physiologic and Standard Sex Steroid Replacement Regimens in Women With Premature Ovarian Failure
NCT01391052	PHASE4	UNKNOWN	Pretreatment With Norethindrone Acetate Prior to Levonorgestrel IUS Insertion for Heavy Menstrual Bleeding
NCT02905890	PHASE4	COMPLETED	The Effect of Norethisterone Enanthate on Recurrent Bacterial Vaginosis
NCT03594604	PHASE4	COMPLETED	Norethindrone for the Delay of Menstruation
NCT04047875	PHASE4	COMPLETED	Treatment of Prolonged Uterine Bleeding of Etonogestrel (ENG)-Releasing Implant
NCT04676061	PHASE4	TERMINATED	Effects of a Progestin on Frequent and/or Prolonged Bleeding With Nexplanon™
NCT05294341	PHASE4	COMPLETED	Metabolism of 0.35mg Norethindrone vs 5mg Norethindrone Acetate
NCT05586724	PHASE3	RECRUITING	Micronized Progesterone Versus Norethisterone Acetate in Combination With Estrogen as Menopausal Hormone Therapy
NCT00212277	PHASE3	COMPLETED	Efficacy and Safety,Long-term Study of Low-dose Oral Contraceptive Pill to Treat Dysmenorrhea.
NCT00212342	PHASE3	COMPLETED	Efficacy and Safety Study of Low Dose Oral Contraceptive Pill to Treat Dysmenorrhea
NCT00229996	PHASE3	COMPLETED	Medical Treatment of Endometriosis-Associated Pelvic Pain
NCT00458458	PHASE3	UNKNOWN	Treatment of Endometriosis With Norethindrone Acetate ( NA) VS. Gonadotropin- Releasing Hormone (GnRH) Agonist (Lupron Depot 11.25 mg)
NCT00477633	PHASE3	COMPLETED	Study of Safety and Efficacy of an Oral Contraceptive
NCT00932321	PHASE3	COMPLETED	Study of Safety and Efficacy of an Oral Contraceptive
NCT03049735	PHASE3	COMPLETED	LIBERTY 1: Efficacy & Safety Study of Relugolix in Women With Heavy Menstrual Bleeding Associated With Uterine Fibroids
NCT03103087	PHASE3	COMPLETED	LIBERTY 2: Efficacy & Safety Study of Relugolix in Women With Heavy Menstrual Bleeding Associated With Uterine Fibroids
NCT03106454	PHASE3	COMPLETED	Ovulation Incidence in Oral Contraceptive Users
NCT03204318	PHASE3	COMPLETED	SPIRIT 1: Efficacy and Safety Study of Relugolix in Women With Endometriosis-Associated Pain
NCT03204331	PHASE3	COMPLETED	SPIRIT 2: Efficacy and Safety Study of Relugolix in Women With Endometriosis-Associated Pain
NCT03271489	PHASE3	COMPLETED	Long-Term Safety Study of Elagolix in Combination With Estradiol/Norethindrone Acetate for the Management of Heavy Menstrual Bleeding Associated With Uterine Fibroids in Premenopausal Women
NCT03343067	PHASE3	TERMINATED	A Study to Evaluate Safety and Efficacy of Elagolix in Participants With Endometriosis With Associated Moderate to Severe Pain
NCT00004763	PHASE2	COMPLETED	Phase II Randomized Study of Leuprolide Vs Oral Contraceptive Therapy Vs Leuprolide and Oral Contraceptive Therapy for Ovarian Hyperandrogenism
NCT00474851	PHASE2	COMPLETED	The Effect of Hormonal Add-Back Therapy in Adolescents Treated With a GnRH Agonist for Endometriosis: A Randomized Trial
NCT00919919	PHASE2	UNKNOWN	Efficacy and Tolerability Study of Progesterone Vaginal Tablets (Endometrin®) in Menopausal Women Treated by Estrogen
NCT01441635	PHASE2	COMPLETED	Safety and Efficacy of Elagolix in Pre-Menopausal Women With Heavy Uterine Bleeding and Uterine Fibroids
NCT01466114	PHASE2	UNKNOWN	Estriol Treatment in Multiple Sclerosis (MS): Effect on Cognition
NCT04948489	PHASE2	WITHDRAWN	IUD and Norethindrone Acetate for Treatment of Endometriosis
NCT00821496	PHASE1	COMPLETED	Evaluate the Effect of VI-0521 on the Pharmacokinetics of Oral Contraceptive in Healthy Female Subjects
NCT01040845	PHASE1	COMPLETED	A Pharmacokinetic Study of Colchicine With an Oral Contraceptive
NCT01209143	PHASE1	COMPLETED	A Study of Pharmacokinetic Drug Interaction Study of the Hedgehog Pathway Inhibitor GDC-0449 in Combination With Rosiglitazone or Combined Oral Contraceptive in Patients With Locally Advanced or Metastatic Solid Tumors That Are Refractory to Standard Therapy or for Whom No Standard Therapy Exists
NCT01340625	PHASE1	COMPLETED	Norethindrone/Ethinyl Estradiol 0.4 mg/35 Mcg Chewable Tablets Under Fasting Conditions
NCT01344369	PHASE1	COMPLETED	Norethindrone/Ethinyl Estradiol 0.4 mg/35 Mcg Chewable Tablets Under Non-Fasted Conditions
NCT02652650	PHASE1	COMPLETED	A Study to Investigate the Effect of JNJ-63623872 at Steady-state on the Steady-state Pharmacokinetics of Ethinylestradiol and Norethindrone
NCT02705963	PHASE1	COMPLETED	A Drug-Drug Interaction Study to Assess the Effect of Trametinib on the Pharmacokinetics of an Oral Contraceptive in Female Patients With Solid Tumors
NCT03262727	PHASE1	COMPLETED	The Effect of BMS-986165 Combined With an Oral Contraceptive (Ethinyl Estradiol/Norethindrone) in Healthy Female Patients
NCT03262740	PHASE1	COMPLETED	The Effect of BMS-986195 Combined With an Oral Contraceptive (Ethinyl Estradiol/Norethindrone) in Healthy Female Patients
NCT03353857	PHASE1	COMPLETED	Drug-drug Interaction Between Rifampicin and Progestins/Ethinylestradiol and Midazolam
NCT04709094	PHASE1	COMPLETED	A Drug Interaction Study of Danicopan
NCT00006133	Not specified	COMPLETED	Randomized Study of Oral Contraceptives or Hormone Replacement Therapy in Women With Systemic Lupus Erythematosus

Clinical evidence (CIViC)

No CIViC predictive evidence (expected for non-precision-medicine drugs).

Pharmacology

Pharmacogenomics

No CPIC/DPWG dosing guideline or drug-level clinical/variant annotations in PharmGKB for this molecule.

Related molecules

Related molecules

Molecules sharing ≥1 of this drug’s curated primary targets, merged from two biobtree sources and ranked by shared-target count, then clinical phase: ChEMBL clinical-stage candidates (development phase ≥2) and PubChem drug-class bioactivity (approved / known drugs acting on the target). Deduplicated by drug name; the drug’s own salt forms are excluded. Note: for a drug with few primary targets a shared-target match can reflect off-target / promiscuous binding rather than the same therapeutic mechanism — the phase ordering surfaces bona-fide therapeutics first.

290 molecules share ≥1 primary target. Top 60 by shared-target count:

Molecule	Source	Status	Shared targets
FIDAXOMICIN	ChEMBL + PubChem	Phase 4 (approved)	PGR
FULVESTRANT	ChEMBL + PubChem	Phase 4 (approved)	PGR
GENTIAN VIOLET	ChEMBL + PubChem	Phase 4 (approved)	PGR
ABIRATERONE	ChEMBL	Phase 4 (approved)	PGR
ACETYLCHOLINE	ChEMBL	Phase 4 (approved)	PGR
ADAPALENE	ChEMBL	Phase 4 (approved)	PGR
ALCLOMETASONE DIPROPIONATE	ChEMBL	Phase 4 (approved)	PGR
ALECTINIB	ChEMBL	Phase 4 (approved)	PGR
AMCINONIDE	ChEMBL	Phase 4 (approved)	PGR
APOMORPHINE	ChEMBL	Phase 4 (approved)	PGR
ARFORMOTEROL	ChEMBL	Phase 4 (approved)	PGR
ARIPIPRAZOLE	ChEMBL	Phase 4 (approved)	PGR
AZATHIOPRINE	ChEMBL	Phase 4 (approved)	PGR
BECLOMETHASONE DIPROPIONATE	ChEMBL	Phase 4 (approved)	PGR
BENPERIDOL	ChEMBL	Phase 4 (approved)	PGR
BENZBROMARONE	ChEMBL	Phase 4 (approved)	PGR
BENZIODARONE	ChEMBL	Phase 4 (approved)	PGR
BETAMETHASONE	ChEMBL	Phase 4 (approved)	PGR
BETAMETHASONE DIPROPIONATE	ChEMBL	Phase 4 (approved)	PGR
BETAMETHASONE VALERATE	ChEMBL	Phase 4 (approved)	PGR
BEXAROTENE	ChEMBL	Phase 4 (approved)	PGR
BICALUTAMIDE	ChEMBL	Phase 4 (approved)	PGR
BIFONAZOLE	ChEMBL	Phase 4 (approved)	PGR
BITHIONOL	ChEMBL	Phase 4 (approved)	PGR
BOSUTINIB	ChEMBL	Phase 4 (approved)	PGR
BUDESONIDE	ChEMBL	Phase 4 (approved)	PGR
BUTOCONAZOLE	ChEMBL	Phase 4 (approved)	PGR
CABOZANTINIB	ChEMBL	Phase 4 (approved)	PGR
CALCIPOTRIENE	ChEMBL	Phase 4 (approved)	PGR
CALCITRIOL	ChEMBL	Phase 4 (approved)	PGR
CANDESARTAN CILEXETIL	ChEMBL	Phase 4 (approved)	PGR
CANRENONE	ChEMBL	Phase 4 (approved)	PGR
CARBARIL	ChEMBL	Phase 4 (approved)	PGR
CASPOFUNGIN	ChEMBL	Phase 4 (approved)	PGR
CEFAMANDOLE	ChEMBL	Phase 4 (approved)	PGR
CEFMENOXIME	ChEMBL	Phase 4 (approved)	PGR
CEFTAZIDIME	ChEMBL	Phase 4 (approved)	PGR
CEFTIZOXIME	ChEMBL	Phase 4 (approved)	PGR
CEFTRIAXONE	ChEMBL	Phase 4 (approved)	PGR
CEFUROXIME	ChEMBL	Phase 4 (approved)	PGR
CEPHRADINE	ChEMBL	Phase 4 (approved)	PGR
CHLORHEXIDINE	ChEMBL	Phase 4 (approved)	PGR
CHLORMADINONE	ChEMBL	Phase 4 (approved)	PGR
CHOLECALCIFEROL	ChEMBL	Phase 4 (approved)	PGR
CICLESONIDE	ChEMBL	Phase 4 (approved)	PGR
CLOBETASOL PROPIONATE	ChEMBL	Phase 4 (approved)	PGR
CLOCORTOLONE PIVALATE	ChEMBL	Phase 4 (approved)	PGR
CLOMIPHENE	ChEMBL	Phase 4 (approved)	PGR
CYCLOFENIL	ChEMBL	Phase 4 (approved)	PGR
DANAZOL	ChEMBL	Phase 4 (approved)	PGR
DAUNORUBICIN	ChEMBL	Phase 4 (approved)	PGR
DEFLAZACORT	ChEMBL	Phase 4 (approved)	PGR
DEQUALINIUM	ChEMBL	Phase 4 (approved)	PGR
DESOGESTREL	ChEMBL	Phase 4 (approved)	PGR
DESONIDE	ChEMBL	Phase 4 (approved)	PGR
DESOXIMETASONE	ChEMBL	Phase 4 (approved)	PGR
DESOXYCORTICOSTERONE PIVALATE	ChEMBL	Phase 4 (approved)	PGR
DEXAMETHASONE	ChEMBL	Phase 4 (approved)	PGR
DIETHYLPROPION	ChEMBL	Phase 4 (approved)	PGR
DIETHYLSTILBESTROL	ChEMBL	Phase 4 (approved)	PGR