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Mifepristone

Progesterone receptor modulators · given by oral · on the market since 2000

5
Leads
30.7M
People
3
Makers
0
How abandoned
01

What it's made of

Each functional group on the molecule does a specific, predictable job.

STICKS PERMANENTLY

Michael acceptor

What it does. Reacts with the sulfur groups on proteins, forming a permanent bond. The cell reads this as a chemical stress signal and switches on its whole antioxidant defence programme.

What it opens up. Any disease driven by oxidative stress or chronic inflammation, because the drug does not treat the disease so much as turn on the body's own repair response.

CARRIES THE MAIN JOB

Steroid backbone

What it does. Recognised by the receptors that sit directly on DNA and switch genes on and off. Small changes to the decoration around this frame swing the molecule between completely different hormone systems.

What it opens up. Cross-hormone repurposing: a diuretic that also blocks a hormone receptor becomes an acne drug, a hair-loss drug, and a heart-failure drug.

02

Where it can get to

Predicted from molecular weight, lipophilicity, polar surface area and hydrogen-bond donor count. A drug can only act where it distributes, so this constrains which conditions are addressable before any biology is considered. derived

Easily
Systemic circulation
Absorbed from the gut and distributed in plasma.
Partly
Central nervous system
Crosses the blood–brain barrier.
No
Intestinal lumen only
Poorly absorbed. Acts locally in the gut with minimal systemic exposure.
Partly
Skin
Crosses the stratum corneum. Viable as a topical.
No
Urinary tract
Cleared unchanged in urine. Local concentration exceeds plasma.
03

What it binds — and whether we can reach it · 2 of 2 reachable

Binding affinity is only meaningful against the plasma concentration reached at the approved dose. A target requiring higher concentrations cannot be engaged in a patient, whatever the in vitro potency. Most repurposing hypotheses fail at this step, and it is rarely checked before a trial is proposed. measured

Values are pAct — the negative logarithm of the molar concentration at which the drug half-occupies the target. Each whole step is a tenfold difference in potency: 9.0 = 1 nanomolar, 6.0 = 1 micromolar, 5.0 = 10 micromolar. Oral drugs typically reach 0.1–10 micromolar in plasma, so roughly 6.0 is the threshold below which a target cannot be reached at a tolerated dose. Figures come from DrugCentral’s curated binding data.
NR3C1
Nuclear hormo · antagonist
9
Engaged easily
PGR
Nuclear hormo · antagonist
8.74
Engaged easily
04

New uses, and who is already trying them

One card per candidate indication: the reasoning link by link, the evidence tier that governs how strongly it can be stated, and any registered trials.

5 of the 88 conditions linked to this drug’s targets have been checked against trial records so far. The rest are not ruled out — they are unchecked.

3 possible uses were rejected for pushing the wrong way. The target is linked to the condition, but the drug modulates it in the wrong direction.

Not yet used for these — 5

glucocorticoid resistance

Tried in people

It showed an effect in a human trial that was not followed up.

The condition
No description on file.
NR3C1 · nuclear receptor subfamily 3 group C member 1
Receptor for glucocorticoids (GC) (PubMed:27120390, PubMed:37478846). Has a dual mode of action: as a transcription factor that binds to glucocorticoid response elements (GRE), both for nuclear and mitochondrial DNA, and as a modulator of other transcription factors (PubMed:28139699). Affects inflammatory responses, cellular proliferation and differentiation in target tissues. Involved in chromatin remodeling (PubMed:9590696). Plays a role in rapid mRNA degradation by binding to the 5' UTR of target mRNAs and inter
Phase 2 done, then stopped
A Phase 2 trial finished and was not followed by Phase 3. Dosing and safety in this population are already established.
NCT01294319 Evaluation of Cortisol Resistance in You · Ph 2 · 51 people
+3 more on ClinicalTrials.gov
What would kill it. Direction conflict, unless the variant has been assigned the wrong functional class — a known failure mode of consequence-based annotation.

chronic obstructive pulmonary disease

Rejected — wrong way

It would be expected to worsen this condition. The genetic evidence indicates this condition requires the opposite modulation of the target. Shown rather than filtered so the direction check can be audited.

The condition
A chronic and progressive lung disorder characterized by the loss of elasticity of the bronchial tree and the air sacs, destruction of the air sacs wall, thickening of the bronchial wall, and mucous accumulation in the bronchial tree. The pathologic changes result in the disruption of the air flow in the bronchial airways. Signs and symptoms include shortness of breath, wheezing, productive cough, and chest tightness. The two main types of chronic obstructive pulmonary disease are chronic obstructive bronchitis and
NR3C1 · nuclear receptor subfamily 3 group C member 1
Receptor for glucocorticoids (GC) (PubMed:27120390, PubMed:37478846). Has a dual mode of action: as a transcription factor that binds to glucocorticoid response elements (GRE), both for nuclear and mitochondrial DNA, and as a modulator of other transcription factors (PubMed:28139699). Affects inflammatory responses, cellular proliferation and differentiation in target tissues. Involved in chromatin remodeling (PubMed:9590696). Plays a role in rapid mRNA degradation by binding to the 5' UTR of target mRNAs and inter
Nobody has tried this
No registered trial of this drug in this condition.
What would kill it. Direction conflict, unless the variant has been assigned the wrong functional class — a known failure mode of consequence-based annotation.

multiple sclerosis

Rejected — wrong way

It would be expected to worsen this condition. The genetic evidence indicates this condition requires the opposite modulation of the target. Shown rather than filtered so the direction check can be audited.

The condition
A progressive autoimmune disorder affecting the central nervous system resulting in demyelination. Patients develop physical and cognitive impairments that correspond with the affected nerve fibers.
NR3C1 · nuclear receptor subfamily 3 group C member 1
Receptor for glucocorticoids (GC) (PubMed:27120390, PubMed:37478846). Has a dual mode of action: as a transcription factor that binds to glucocorticoid response elements (GRE), both for nuclear and mitochondrial DNA, and as a modulator of other transcription factors (PubMed:28139699). Affects inflammatory responses, cellular proliferation and differentiation in target tissues. Involved in chromatin remodeling (PubMed:9590696). Plays a role in rapid mRNA degradation by binding to the 5' UTR of target mRNAs and inter
Nobody has tried this
No registered trial of this drug in this condition.
What would kill it. Direction conflict, unless the variant has been assigned the wrong functional class — a known failure mode of consequence-based annotation.

endometriosis

Tried in people

It showed an effect in a human trial that was not followed up.

The condition
The growth of functional endometrial tissue in anatomic sites outside the uterine body. It most often occurs in the pelvic organs.
PGR · progesterone receptor
The steroid hormones and their receptors are involved in the regulation of eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues. Depending on the isoform, progesterone receptor functions as a transcriptional activator or repressor. {ECO:0000269|PubMed:10757795, ECO:0000269|PubMed:1587864, ECO:0000269|PubMed:37478846, ECO:0000269|PubMed:9407067, ECO:0000305}.
Phase 2 done, then stopped
A Phase 2 trial finished and was not followed by Phase 3. Dosing and safety in this population are already established.
NCT02271958 Mifepristone 2.5, 5, 10 mg Versus Placeb · Ph 2 · 360 people
What would kill it. Direction conflict, unless the variant has been assigned the wrong functional class — a known failure mode of consequence-based annotation.

rheumatoid arthritis

Rejected — wrong way

It would be expected to worsen this condition. The genetic evidence indicates this condition requires the opposite modulation of the target. Shown rather than filtered so the direction check can be audited.

The condition
A chronic, systemic autoimmune disorder characterized by inflammation in the synovial membranes and articular surfaces. It manifests primarily as a symmetric, erosive polyarthritis that spares the axial skeleton and is typically associated with the presence in the serum of rheumatoid factor.
NR3C1 · nuclear receptor subfamily 3 group C member 1
Receptor for glucocorticoids (GC) (PubMed:27120390, PubMed:37478846). Has a dual mode of action: as a transcription factor that binds to glucocorticoid response elements (GRE), both for nuclear and mitochondrial DNA, and as a modulator of other transcription factors (PubMed:28139699). Affects inflammatory responses, cellular proliferation and differentiation in target tissues. Involved in chromatin remodeling (PubMed:9590696). Plays a role in rapid mRNA degradation by binding to the 5' UTR of target mRNAs and inter
Nobody has tried this
No registered trial of this drug in this condition.
What would kill it. Direction conflict, unless the variant has been assigned the wrong functional class — a known failure mode of consequence-based annotation.
05

Why nobody will fund it

3 companies make this across 3 approved products. With that many manufacturers the price has fallen to production cost. A company funding a trial could not recover it — competitors could market the same molecule for the new indication immediately, without contributing.

How abandoned it is0 / 100
0 to 100, calculated from manufacturer count, remaining patent or exclusivity, and whether any reformulation route to exclusivity is still open. 100 means no route to commercial return exists. The weights behind it are unsourced.
THE ONE WAY A COMPANY COULD STILL OWN IT
injectableinhaledmodified-release

A new route or dosage form qualifies for a 505(b)(2) application, which carries three years of exclusivity for that formulation. It is the only remaining route to exclusivity on a generic molecule.

06

What it would cost to find out

Derived, not quoted. Events needed is 4(zα+zβ)²/ln(HR)²; enrolment is that divided by the event rate and follow-up. The 1/ln(HR)² term dominates: halving the detectable effect size roughly quadruples enrolment. derived

0.75
Lower = bigger effect = smaller trial
8.0%
2 yr
$32K
Unsourced placeholder
379
Events needed
3K
Patients
$93M
Trial cost
assumed
$8.62
Per person reached
assumed

Cost per person reached is the relevant metric for a non-commercial funder, since there is no revenue to set against the outlay.

07

Ask for ideas nobody has listed

Reasons from the functional groups and distribution above, excluding conditions already listed. Output is hypotheses for falsification, not findings. Not medical advice.

08

Who might pay for the trial

Trials of off-patent drugs are rarely funded by venture capital or pharma. They are paid for by government grants and disease foundations. Here is who has funded work on this molecule before, what federal mechanisms are open now, and which foundations fund trials in the disease areas it touches. measured

Federal grants that name this medicine
241 grants on NIH RePORTER
5I01CX001917-05(VA · Veterans Health Administration)Active
Phase IIa Trial of a Selective Glucocorticoid Receptor Antagonist in the Treatment ofVeterans with Posttraumatic Stress Disorder (PTSD)
PI: Neylan, Thomas C · Veterans Affairs Med Ctr San Francisco, San Francisco, CA · through 2026-12
1R01EB039067-01(NIBIB · National Institute of Biomedical Imaging)Active
$328K (2026)
Development of a Label-Free Optical Probe for In Situ Quantification of Cervical Remodeling in Pregnancy
PI: Ramella Roman, Jessica C · Florida International University, Miami, FL · through 2030-03
7R01HL178848-02(NHLBI · National Heart, Lung & Blood Institute)Active
$697K (2026)
Dysregulation of sphingolipid metabolism and signaling in LAM
PI: Yu, Jane · University Of Florida, Gainesville, FL · through 2029-05
Open federal programmes that would fund this work

Open notices with an explicit mandate to fund work on approved or off-patent molecules.

RFA-CA-25-033National Institutes of HealthForecast — not open yet
Glioblastoma Therapeutics Network (GTN; U19 Clinical Trial Required)
RFA-FD-25-020Food and Drug Administrationcloses 05/16/2028
Reissue of RFA-FD-23-001- Clinical Studies of Orphan Products Addressing Unmet
FOR-FD-25-020Food and Drug AdministrationForecast — not open yet
Clinical Studies of Orphan Products Addressing Unmet Needs of Rare Diseases (R
FOR-FD-25-001Food and Drug AdministrationForecast — not open yet
Clinical Trials Addressing Unmet Needs of Rare Neurodegenerative Diseases (R01
RFA-TR-25-002National Institutes of Healthcloses 07/02/2027
Preclinical Proof of Concept Studies for Rare Diseases (R21 Clinical Trial Not
PAR-25-374National Institutes of Healthcloses 05/07/2028
Translational Bioinformatics and Experimental Approaches to Advance Drug Repos
HT942526PRCRPCTADefense Health Agency Contracting Activity -closes 10/05/2026
DoW Peer Reviewed Cancer, Clinical Trial Award
PAR-26-049National Institutes of HealthForecast — not open yet
Establishing Pediatric CNS Pharmacodynamic Measures as Tools to Enable Psychia
Showing 8 of 990 currently open under this category on Grants.gov, matched to the disease areas this drug touches. derived Browse all 990 on Grants.gov ↗
Funders beyond the federal system

Grants.gov lists US federal money. Many off-patent drug trials are supported by disease foundations and nonprofits. These are matched to the body systems this drug touches. assumed

Matched by disease area, not by molecule — a foundation appearing here funds work in a field this drug touches.
09

Who manufactures it

Companies holding an approved abbreviated application for this molecule in the United States, from the FDA Orange Book. Supply already exists at scale, so a trial would not need a manufacturing programme — but any of these could also be a partner, or an objector.

Evita Solutions LlcGenbiopro IncTeva Pharmaceuticals Usa Inc
3
Manufacturers
companies with their own approval
3
Approved products
distinct strengths and forms
1
Routes
oral
2000
Oldest product still sold
approval year of the earliest product still on the market
ALSO SOLD AS
KORLYMMIFEPREX

Nothing on this page is medical advice. Candidate uses are unproven hypotheses derived from public data; established uses are listed for verification only. Figures carry their provenance inline — anything marked assumed or derived is not a measurement.

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