Pioglitazone Hydrochloride

Combinations of oral blood glucose lowering drugs · Thiazolidinediones · given by oral · on the market since 1999

Leads

21.3M

People

Makers

How abandoned

What it's made of

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

No standard functional groups matched.

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.

Easily

Central nervous system

Crosses the blood–brain barrier.

Intestinal lumen only

Poorly absorbed. Acts locally in the gut with minimal systemic exposure.

Easily

Skin

Crosses the stratum corneum. Viable as a topical.

Partly

Urinary tract

Cleared unchanged in urine. Local concentration exceeds plasma.

What it binds — and whether we can reach it · 1 of 1 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.

PPARG

Nuclear hormo · agonist

6.23

Just reachable

Target	Kind	Action	Affinity (pAct)	Can it be engaged?
PPARG	Nuclear hormo	agonist	6.23	Just reachable

This molecule concentrates in urine. Local concentration therefore exceeds plasma, so targets that look unreachable on a plasma reading may still be engaged. assumed

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

Not yet used for these — 3

PPARG-related familial partial lipodystrophy

Wide open

It acts on a target linked to this disease; untested, and the direction of effect is unverified.

The condition

No description on file.

PPARG · peroxisome proliferator activated receptor gamma

Ligand-activated transcription factor that forms obligate heterodimers with the retinoic acid receptor and acts as a key regulator of biological processes, such as adipocyte differentiation, lipid metabolism, glucose homeostasis and beta-oxidation of fatty acids (PubMed:16150867, PubMed:20829347, PubMed:23525231, PubMed:8702406, PubMed:8706692, PubMed:9065481). Activated by lipid ligands: binds peroxisome proliferators, such as hypolipidemic drugs, and fatty acids, such as prostaglandin J2 metabolites (PubMed:16150

Open Targets scores each kind of evidence from 0.00 to 1.00 for this exact pairing — PPARG and PPARG-related familial partial lipodystrophy. The score reflects how much evidence of that kind exists and how consistent it is. It is not a probability that the drug works. Rows are ordered by how much each kind counts toward the evidence figure used in the ranking, not by its raw score, because the two disagree: literature co-occurrence saturates near 1.00 on almost any well-studied pair, while genetic association rarely exceeds 0.70 even when causal.

Genetic association0.85 / 1.00

Inherited variants in this gene alter disease risk in human populations. The datatype most predictive of later clinical success.55% of evidence score

Animal model0.61 / 1.00

Altering this gene in animals reproduces or relieves the disease phenotype.15% of evidence score

Curated genetic literature0.86 / 1.00

Gene–disease links curated from published genetic studies.5% of evidence score

Literature co-occurrence0.20 / 1.00

Gene and condition appear together in published text. Reflects publication volume, not causal evidence.2% of evidence score

Nobody has tried this

No registered trial of this drug in this condition.

What would kill it. A null trial, or pharmacokinetic data showing the drug does not reach PPARG in the relevant tissue at tolerated doses.

ulcerative colitis

Wide open

It acts on a target linked to this disease; untested, and the direction of effect is unverified.

The condition

An inflammatory bowel disease involving the mucosal surface of the large intestine and rectum. It may present with an acute or slow onset and follows an intermittent or continuous course. Signs and symptoms include abdominal pain, diarrhea, fever, weight loss, and intestinal hemorrhage.

PPARG · peroxisome proliferator activated receptor gamma

Open Targets scores each kind of evidence from 0.00 to 1.00 for this exact pairing — PPARG and ulcerative colitis. The score reflects how much evidence of that kind exists and how consistent it is. It is not a probability that the drug works. Rows are ordered by how much each kind counts toward the evidence figure used in the ranking, not by its raw score, because the two disagree: literature co-occurrence saturates near 1.00 on almost any well-studied pair, while genetic association rarely exceeds 0.70 even when causal.

Literature co-occurrence0.32 / 1.00

Gene and condition appear together in published text. Reflects publication volume, not causal evidence.2% of evidence score

Clinical0.99 / 1.00

Derived from clinical or trial records.not counted

Expression0.15 / 1.00

Transcript levels differ in diseased tissue. Associative only.not counted

Nobody has tried this

No registered trial of this drug in this condition.

What would kill it. A null trial, or pharmacokinetic data showing the drug does not reach PPARG in the relevant tissue at tolerated doses.

morbid obesity

Wide open

It acts on a target linked to this disease; untested, and the direction of effect is unverified.

The condition

An excess of body weight, normally defined as an individual with a body mass index greater than 35 or a body weight greater than one hundred percent of ideal body weight.

PPARG · peroxisome proliferator activated receptor gamma

Open Targets scores each kind of evidence from 0.00 to 1.00 for this exact pairing — PPARG and morbid obesity. The score reflects how much evidence of that kind exists and how consistent it is. It is not a probability that the drug works. Rows are ordered by how much each kind counts toward the evidence figure used in the ranking, not by its raw score, because the two disagree: literature co-occurrence saturates near 1.00 on almost any well-studied pair, while genetic association rarely exceeds 0.70 even when causal.

Genetic association0.70 / 1.00

Inherited variants in this gene alter disease risk in human populations. The datatype most predictive of later clinical success.55% of evidence score

Curated genetic literature0.76 / 1.00

Gene–disease links curated from published genetic studies.5% of evidence score

Literature co-occurrence0.21 / 1.00

Gene and condition appear together in published text. Reflects publication volume, not causal evidence.2% of evidence score

Nobody has tried this

No registered trial of this drug in this condition.

What would kill it. A null trial, or pharmacokinetic data showing the drug does not reach PPARG in the relevant tissue at tolerated doses.

Already used for these — 2

Established practice, listed so the method can be checked against what is already known.

type 2 diabetes mellitus

Already in use

It is already used for this.

The condition

A type of diabetes mellitus that is characterized by insulin resistance or desensitization and increased blood glucose levels. This is a chronic disease that can develop gradually over the life of a patient and can be linked to both environmental factors and heredity.

PPARG · peroxisome proliferator activated receptor gamma

Open Targets scores each kind of evidence from 0.00 to 1.00 for this exact pairing — PPARG and type 2 diabetes mellitus. The score reflects how much evidence of that kind exists and how consistent it is. It is not a probability that the drug works. Rows are ordered by how much each kind counts toward the evidence figure used in the ranking, not by its raw score, because the two disagree: literature co-occurrence saturates near 1.00 on almost any well-studied pair, while genetic association rarely exceeds 0.70 even when causal.

Genetic association0.89 / 1.00

Inherited variants in this gene alter disease risk in human populations. The datatype most predictive of later clinical success.55% of evidence score

Animal model0.59 / 1.00

Altering this gene in animals reproduces or relieves the disease phenotype.15% of evidence score

Curated genetic literature0.92 / 1.00

Gene–disease links curated from published genetic studies.5% of evidence score

Literature co-occurrence0.95 / 1.00

Gene and condition appear together in published text. Reflects publication volume, not causal evidence.2% of evidence score

Clinical1.00 / 1.00

Derived from clinical or trial records.not counted

In routine use

Established practice for this condition, not a new candidate.

NCT02292290 Trial for People With Established Type 2 · Ph 4 · 99 people

+14 more on ClinicalTrials.gov

What would kill it. A null trial, or pharmacokinetic data showing the drug does not reach PPARG in the relevant tissue at tolerated doses.

diabetes mellitus

Already in use

It is already used for this.

The condition

A metabolic disorder characterized by abnormally high blood sugar levels due to diminished production of insulin or insulin resistance/desensitization.

PPARG · peroxisome proliferator activated receptor gamma

Open Targets scores each kind of evidence from 0.00 to 1.00 for this exact pairing — PPARG and diabetes mellitus. The score reflects how much evidence of that kind exists and how consistent it is. It is not a probability that the drug works. Rows are ordered by how much each kind counts toward the evidence figure used in the ranking, not by its raw score, because the two disagree: literature co-occurrence saturates near 1.00 on almost any well-studied pair, while genetic association rarely exceeds 0.70 even when causal.

Genetic association0.80 / 1.00

Inherited variants in this gene alter disease risk in human populations. The datatype most predictive of later clinical success.55% of evidence score

Animal model0.59 / 1.00

Altering this gene in animals reproduces or relieves the disease phenotype.15% of evidence score

Literature co-occurrence0.87 / 1.00

Gene and condition appear together in published text. Reflects publication volume, not causal evidence.2% of evidence score

Clinical0.94 / 1.00

Derived from clinical or trial records.not counted

In routine use

Established practice for this condition, not a new candidate.

NCT02292290 Trial for People With Established Type 2 · Ph 4 · 99 people

+14 more on ClinicalTrials.gov

What would kill it. A null trial, or pharmacokinetic data showing the drug does not reach PPARG in the relevant tissue at tolerated doses.

Why nobody will fund it

11 companies make this across 33 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 is55 / 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

topicalinjectableinhaledmodified-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.

What it would cost to find out

Derived, not quoted. Events needed is 4(z_α+z_β)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

Effect sought (hazard ratio)0.75

Lower = bigger effect = smaller trial

How often the event happens per year8.0%

Follow-up2 yr

Cost per patient$32K

Unsourced placeholder

379

Events needed

Patients

$93M

Trial cost

assumed

$12.43

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.

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.

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

888 grants on NIH RePORTER

5R01AR079445-05(NIAMS · National Institute of Arthritis & Musculoskeletal Diseases)Active

$318K (2026)

Targeting Muscle Fatigability During Cachexia

PI: Pistilli, Emidio Edward · West Virginia University, Morgantown, WV · through 2027-04

View on NIH RePORTER ↗Apply to same mechanism (PA-20-185) ↗

1R01HL180977-01A1(NHLBI · National Heart, Lung & Blood Institute)Active

$747K (2026)

Mechanisms of pain in sickle cell disease

PI: Simone, Donald · University Of Minnesota, Minneapolis, MN · through 2030-04

View on NIH RePORTER ↗Apply to same mechanism (PA-25-301) ↗

5R01DK097554-13(NIDDK · National Institute of Diabetes & Digestive & Kidney Diseases)Active

$685K (2026)

Comparative Effectiveness of Two Initial Combination Therapies in Patients with New Onset Diabetes

PI: Abdul-Ghani, Muhammad · University Of Texas Hlth Science Center, San Antonio, TX · through 2029-02

View on NIH RePORTER ↗Apply to same mechanism (PA-20-183) ↗

See all 888 projects on NIH RePORTER →

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)

Grants.gov (RFA-CA-25-033) ↗Direct listing ↗Who already holds this grant ↗

RFA-FD-25-020Food and Drug Administrationcloses 05/16/2028

Reissue of RFA-FD-23-001- Clinical Studies of Orphan Products Addressing Unmet

Read announcement ↗Grants.gov (RFA-FD-25-020) ↗Direct listing ↗Who already holds this grant ↗

FOR-FD-25-020Food and Drug AdministrationForecast — not open yet

Clinical Studies of Orphan Products Addressing Unmet Needs of Rare Diseases (R

Grants.gov (FOR-FD-25-020) ↗Direct listing ↗Who already holds this grant ↗

FOR-FD-25-001Food and Drug AdministrationForecast — not open yet

Clinical Trials Addressing Unmet Needs of Rare Neurodegenerative Diseases (R01

Grants.gov (FOR-FD-25-001) ↗Direct listing ↗Who already holds this grant ↗

RFA-TR-25-002National Institutes of Healthcloses 07/02/2027

Preclinical Proof of Concept Studies for Rare Diseases (R21 Clinical Trial Not

Read announcement ↗Grants.gov (RFA-TR-25-002) ↗Direct listing ↗Who already holds this grant ↗

PAR-25-374National Institutes of Healthcloses 05/07/2028

Translational Bioinformatics and Experimental Approaches to Advance Drug Repos

Read announcement ↗Grants.gov (PAR-25-374) ↗Direct listing ↗Who already holds this grant ↗

HT942526PRCRPCTADefense Health Agency Contracting Activity -closes 10/05/2026

DoW Peer Reviewed Cancer, Clinical Trial Award

Grants.gov (HT942526PRCRPCTA) ↗Direct listing ↗Who already holds this grant ↗

PAR-26-049National Institutes of HealthForecast — not open yet

Establishing Pediatric CNS Pharmacodynamic Measures as Tools to Enable Psychia

Grants.gov (PAR-26-049) ↗Direct listing ↗Who already holds this grant ↗

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.

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.

Accord Healthcare IncAiping Pharmaceutical IncAnnora Pharma Private Ltd

Manufacturers

companies with their own approval

Approved products

distinct strengths and forms

Routes

oral

1999

Oldest product still sold

approval year of the earliest product still on the market

ALSO SOLD AS

ACTOS

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.

← Back to the full ledger

What it's made of

Where it can get to

What it binds — and whether we can reach it · 1 of 1 reachable

New uses, and who is already trying them

PPARG-related familial partial lipodystrophy

ulcerative colitis

morbid obesity

type 2 diabetes mellitus

diabetes mellitus

Why nobody will fund it

What it would cost to find out

Ask for ideas nobody has listed

Who might pay for the trial

Who manufactures it

Closely related medicines