Treprostinil

Summary

Treprostinil (CHEMBL1237119) is an approved small-molecule platelet aggregation inhibitor (ATC B01AC21) targeting PTGDR, PTGER1, and PTGER2; indicated across 18 conditions including pulmonary arterial hypertension and thrombotic disease.

At a glance

• Status: Approved (max clinical phase 4)
• Modality: Small molecule
• ATC class: B01AC21
• Targets: 6 (PTGDR, PTGER1, PTGER2…)
• Indications: 18 conditions
• Clinical trials: 59
• Chemistry: 390.5 Da · C23H34O5

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL1237119
Name	Treprostinil
Type	Small molecule
Max phase	4
FDA approved	yes
PubChem CID	6918140
ChEBI	CHEBI:50861
ATC	B01AC21
Molecular formula	C23H34O5
Molecular weight	390.5
InChIKey	PAJMKGZZBBTTOY-ZFORQUDYSA-N

SMILES: CCCCC[C@@H](CC[C@H]1[C@@H](C[C@H]2[C@@H]1CC3=C(C2)C(=CC=C3)OCC(=O)O)O)O

IUPAC name: 2-[[(1R,2R,3aS,9aS)-2-hydroxy-1-[(3S)-3-hydroxyoctyl]-2,3,3a,4,9,9a-hexahydro-1H-cyclopenta[g]naphthalen-5-yl]oxy]acetic acid

Pharmacological roles (ChEBI): platelet aggregation inhibitor, vasodilator agent, antihypertensive agent, cardiovascular drug, vitamin K antagonist.

Other ChEBI roles (chemical / environmental): human blood serum metabolite.

Also known as: 15AU81, L-606, L606, LRX -15, LRX-15, Remodulin, Rumodolin, Treprostinil, Treprostinilo, Tresprostinil, Tyvaso, Tyvaso dpi

Parent form; salt/anhydrous children: CHEMBL561157, CHEMBL2107815

Patent coverage: 248 distinct patent families (766 SureChEMBL compound mentions), from 2 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
PTGDR	DP1 receptor	Full agonist	8.4	0.4%	Q13258
PTGER1	EP1 receptor	Full agonist	6.7	0.4%	P34995
PTGER2	EP2 receptor	Full agonist	8.4	0.1%	P43116
PTGER3	EP3 receptor	Full agonist	5.6	2.6%	P43115
PTGER4	EP4 receptor	Agonist	6.1	0.5%	P35408
PTGIR	IP receptor	Full agonist	7.49	0.2%	P43119

Broader ChEMBL bioactivity targets: 4 (assay-derived). Sample: Prostaglandin E2 receptor EP1 subtype, Prostaglandin E2 receptor EP2 subtype, Prostacyclin receptor, Prostaglandin D2 receptor.

Bioactivity

ChEMBL activities: 4 potent at pChembl ≥ 5 of 4 total. Top 100 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
PTGDR	9.22	EC50	0.6	nM	CHEMBL_ACT_24775868
PTGIR	8.72	EC50	1.9	nM	CHEMBL_ACT_24775870
PTGER2	8.21	EC50	6.2	nM	CHEMBL_ACT_24775872
PTGER1	6.54	EC50	285	nM	CHEMBL_ACT_24775874

Target pathways

Aggregated over 6 target gene(s): PTGDR, PTGER1, PTGER2, PTGER3, PTGER4, PTGIR.

Top Reactome pathways

5 total, by targets touching each:

Pathway	Targets	Genes
Prostanoid ligand receptors	6	PTGDR, PTGER1, PTGER2, PTGER3, PTGER4, PTGIR
G alpha (s) signalling events	4	PTGDR, PTGER2, PTGER4, PTGIR
Prostacyclin signalling through prostacyclin receptor	1	PTGIR
G alpha (q) signalling events	1	PTGER1
G alpha (i) signalling events	1	PTGER3

Dominant GO biological processes

GO term	Targets
inflammatory response	6
G protein-coupled receptor signaling pathway	6
positive regulation of cytosolic calcium ion concentration	6
signal transduction	6
adenylate cyclase-activating G protein-coupled receptor signaling pathway	5
response to lipopolysaccharide	3
phospholipase C-activating G protein-coupled receptor signaling pathway	2
response to prostaglandin E	2
cellular response to prostaglandin E stimulus	2
male sex determination	1
sleep	1
mast cell degranulation	1
adenosine metabolic process	1
cellular response to prostaglandin D stimulus	1
adenylate cyclase-activating dopamine receptor signaling pathway	1

Indications & clinical

Indications

3 approved indications. FDA phase 4, plus an anticancer drug’s labelled cancer uses (which ChEMBL often logs at phase 3).

Indication	Phase	MONDO	EFO
pulmonary arterial hypertension	4	MONDO:0015924	EFO:0001361
thrombotic disease	4	MONDO:0000831	HP:0004419
pulmonary hypertension	4	MONDO:0005149	MONDO:0005149

12 diseases in clinical trials (phase 1–3, investigational — not approved indications). Highest ChEMBL trial phase per disease; a non-cancer approved use is occasionally logged at phase 3 here.

Disease (in trials)	Phase	MONDO	EFO
idiopathic pulmonary fibrosis	3	MONDO:0800504	EFO:0000768
interstitial lung disease	3	MONDO:0015925	EFO:0004244
pulmonary fibrosis	3	MONDO:0002771	EFO:0009448
chronic obstructive pulmonary disease	2	MONDO:0005002	EFO:0000341
ischemic disease	2	MONDO:0005053	EFO:0000556
congenital heart disease	2	MONDO:0005453	EFO:0005207
peripheral vascular disease	2	MONDO:0005294	EFO:0003875
persistent fetal circulation syndrome	2	MONDO:0022430	EFO:1001103
adult acute respiratory distress syndrome	2	MONDO:0100130	MONDO:0100130
ischemia reperfusion injury	1	MONDO:0005203	EFO:0002687
systemic sclerosis	1	MONDO:0005100	EFO:0000717
type 1 diabetes mellitus	1	MONDO:0005147	MONDO:0005147

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

Clinical trials

Total trials: 59.

Phase distribution

Phase	Trials
PHASE3	17
PHASE2	12
PHASE4	11
Not specified	7
PHASE1	5
PHASE1/PHASE2	3
PHASE2/PHASE3	2
EARLY_PHASE1	2

Top trials by phase / activity

NCT	Phase	Status	Title
NCT05203510	PHASE4	ACTIVE_NOT_RECRUITING	A Study of a Mean Pulmonary Artery Pressure-Targeted Approach With Early and Rapid Treprostinil Therapy to Reverse Right Ventricular Remodeling in Participants With Pulmonary Arterial Hypertension
NCT07112183	PHASE4	RECRUITING	Open Label Treprostinil Raynaud’s Study
NCT00439946	PHASE4	TERMINATED	Safety, Efficacy, and Treatment Satisfaction Switching From Flolan to Remodulin Using the Crono Five Ambulatory Pump in Patients With PAH
NCT00741819	PHASE4	COMPLETED	Safety Evaluation of Inhaled Treprostinil Administration Following Transition From Inhaled Ventavis in Pulmonary Arterial Hypertension (PAH) Subjects
NCT01268553	PHASE4	COMPLETED	Transition From Injectable Prostacyclin Medication to Inhaled Prostacyclin Medication
NCT01305252	PHASE4	COMPLETED	A 48-week Study of the Effect of Dual Therapy (Inhaled Treprostinil and Tadafafil) Versus Monotherapy (Tadalafil).
NCT02847260	PHASE4	COMPLETED	Safety and Tolerability of Rapid Dose Titration of Subcutaneous Remodulin® Therapy in PAH Subjects (RAPID)
NCT02882126	PHASE4	WITHDRAWN	An Open Label Extension Study to Evaluate the Safety of Continued Therapy of Subcutanous Remodulin® in Pulmonary Arterial Hypertension
NCT03055221	PHASE4	COMPLETED	TRUST-2: Safety and Efficacy of Intravenous Remodulin® in Patients in India With Pulmonary Arterial Hypertension (PAH)
NCT03835676	PHASE4	UNKNOWN	Effects of Treprostinil on Right Ventricular Structure and Function in Patients With Pulmonary Arterial Hypertension
NCT06605326	PHASE4	COMPLETED	Subcutaneous Treprostinil as a Bridge to Lung Transplantation in Severe Pulmonary Hypertension: A Single-Arm Retrospective Study
NCT04905693	PHASE3	ENROLLING_BY_INVITATION	Extension Study of Inhaled Treprostinil in Subjects With Fibrotic Lung Disease
NCT05943535	PHASE3	RECRUITING	Study of the Efficacy and Safety of Inhaled Treprostinil in Subjects With Progressive Pulmonary Fibrosis (TETON-PPF)
NCT07285655	PHASE3	RECRUITING	A Phase 3 Study to Evaluate the Safety and Efficacy L606 in Participants With PH-ILD
NCT00004497	PHASE3	COMPLETED	Phase III Randomized Study of UT-15 in Patients With Primary Pulmonary Hypertension
NCT00147199	PHASE3	COMPLETED	Clinical Investigation Into Inhaled Treprostinil Sodium in Patients With Severe Pulmonary Arterial Hypertension (PAH)
NCT00325403	PHASE3	COMPLETED	FREEDOM - M: Oral Treprostinil as Monotherapy for the Treatment of Pulmonary Arterial Hypertension (PAH)
NCT00325442	PHASE3	COMPLETED	FREEDOM-C: Oral Treprostinil in Combination With an Endothelin Receptor Antagonist (ERA) and/or a Phosphodiesterase-5 (PDE-5) Inhibitor for the Treatment of Pulmonary Arterial Hypertension (PAH)
NCT01027949	PHASE3	COMPLETED	An Open-Label Extension Trial of UT-15C Sustained-release (SR) in Subjects With Pulmonary Arterial Hypertension
NCT01557647	PHASE3	WITHDRAWN	Safety and Efficacy of Inhaled Treprostinil in Patients With PAH
NCT01557660	PHASE3	WITHDRAWN	Inhaled Treprostinil for PAH: Open-label Extension
NCT02630316	PHASE2/PHASE3	COMPLETED	Safety and Efficacy of Inhaled Treprostinil in Adult PH With ILD Including CPFE
NCT02633293	PHASE2/PHASE3	TERMINATED	An Open Label Extension Study to Evaluate Inhaled Treprostinil in Adult PH With ILD Including CPFE
NCT02865733	PHASE3	COMPLETED	Study of Remodulin® in Pediatric Pulmonary Hypertension With Single Ventricular Physiology After Fontan Surgery
NCT02999906	PHASE3	WITHDRAWN	Study to Compare Triple Therapy (Oral Treprostinil, Ambrisentan, and Tadalafil) With Dual Therapy (Ambrisentan, Tadalafil, and Placebo) in Subjects With Pulmonary Arterial Hypertension
NCT03037580	PHASE3	TERMINATED	Oral Treprostinil in Subjects With Pulmonary Hypertension Associated With Heart Failure With Preserved Ejection Fraction
NCT03043651	PHASE3	TERMINATED	Open-label Extension of Oral Treprostinil in Subjects With PH Associated With HFpEF
NCT03055234	PHASE3	WITHDRAWN	Study to Evaluate Efficacy and Safety of Oral Treprostinil in Subjects With Pulmonary Hypertension (PH) Associated With Sickle Cell Disease (SCD)
NCT04708782	PHASE3	COMPLETED	Study of Efficacy and Safety of Inhaled Treprostinil in Subjects With Idiopathic Pulmonary Fibrosis
NCT05255991	PHASE3	COMPLETED	Multinational Study of Efficacy and Safety of Inhaled Treprostinil in Subjects With Idiopathic Pulmonary Fibrosis
NCT04005469	PHASE1/PHASE2	RECRUITING	Safety and Efficacy of Treprostinil (Remodulin®) In Reducing Ischemia-Reperfusion Injury During Kidney Transplantation
NCT07177703	PHASE2	NOT_YET_RECRUITING	Efficacy and Safety of Treprostinil in Intermediate-Risk Pulmonary Arterial Hypertension
NCT00703339	PHASE2	TERMINATED	Effects of Inhaled Treprostinil Sodium for the Treatment of Pulmonary Hypertension Associated With Idiopathic Pulmonary Fibrosis
NCT00705133	PHASE2	COMPLETED	Treprostinil Therapy For Patients With Interstitial Lung Disease And Severe Pulmonary Arterial Hypertension
NCT01082484	PHASE1/PHASE2	COMPLETED	Cutaneous Iontophoresis of Iloprost and Treprostinil in Healthy Volunteers
NCT02178566	PHASE2	TERMINATED	Pulmonary Rehab in Chronic Obstructive Pulmonary Disease (COPD): Response to Tyvaso
NCT02276872	PHASE2	COMPLETED	Safety, Tolerability, and Pharmacokinetics of Oral Treprostinil in Pediatric PAH Patients Aged 7 to 17 Years
NCT02603068	PHASE2	WITHDRAWN	Oral Treprostinil in Subjects With Pulmonary Hypertension Associated With Pulmonary Fibrosis
NCT02663895	PHASE2	COMPLETED	Safety and Efficacy of Oral Treprostinil in the Treatment of Calcinosis in Patients With Systemic Sclerosis
NCT02769624	PHASE2	TERMINATED	Acute Effects of Inhaled Treprostinil in Fontan Patients
NCT03012646	PHASE2	WITHDRAWN	Safety and Tolerability of Inhaled Treprostinil in Adult PH Due to COPD
NCT03016468	PHASE2	WITHDRAWN	Safety of Transition From Selexipag to Remodulin® Then Oral Treprostinil in Symptomatic Adult PAH
NCT03654989	PHASE1/PHASE2	TERMINATED	Iontophoresis of Treprostinil to Enhance Wound Healing in Diabetic Foot Skin Ulcers
NCT03814317	PHASE2	COMPLETED	Inhaled Treprostinil in Sarcoidosis Patients With Pulmonary Hypertension
NCT05564637	PHASE2	COMPLETED	A Study of Treprostinil to Treat Interstitial Lung Disease Pulmonary Hypertension
NCT01481974	PHASE1	COMPLETED	Safety and Efficacy of Treprostinil in Ischemia and Reperfusion Injury in Adult Orthotopic Liver Transplantation
NCT02770521	PHASE1	COMPLETED	A Study of Treprostinil and a New Formulation of LY900014 in Healthy Japanese Participants
NCT03803163	PHASE1	TERMINATED	A Safety, Tolerability and Pharmacokinetics Study of TransCon Treprostinil in Healthy Adult Male Volunteers
NCT04675944	PHASE1	COMPLETED	Effect of BIA 5-1058 on the Steady State Pharmacokinetics of Treprostinil
NCT05067270	PHASE1	COMPLETED	A Study of Infusion Site Pain After Infusion of Excipients in Participants With Type 1 Diabetes Mellitus
NCT07116681	EARLY_PHASE1	NOT_YET_RECRUITING	Effects of Inhaled Treprostinil on Exercise Performance in Exercise Induced Pulmonary Hypertension
NCT02583789	EARLY_PHASE1	COMPLETED	Assess Efficacy of of Oral Treprostinil in Patients With Symptomatic Primary or Secondary Raynaud’s Phenomenon
NCT03045029	Not specified	ACTIVE_NOT_RECRUITING	ADAPT - A Patient Registry of the Real-world Use of Orenitram®
NCT05572996	Not specified	AVAILABLE	Inhaled Treprostinil Expanded Access Program in Pulmonary Hypertension Associated With Interstitial Lung Disease
NCT06603285	Not specified	NOT_YET_RECRUITING	A Study to Observe the Safety, Tolerability, and Efficacy of Remodulin
NCT01028651	Not specified	COMPLETED	A Study to Assess the Safety and Efficacy of Treprostinil to Facilitate Liver Transplantation in Patients With Portopulmonary Hypertension
NCT01980979	Not specified	WITHDRAWN	Efficacy of Remodulin in Adults With Congenital Heart Disease (ACHD) and Pulmonary Hypertension
NCT02498444	Not specified	TERMINATED	Perioperative Treprostinil in Pediatric Patients Undergoing the Fontan Operation
NCT03888365	Not specified	COMPLETED	Patient Global Impression Questions for Activity-Induced Symptoms in Participants With PAH

Clinical evidence (CIViC)

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

Pharmacology

Pharmacogenomics

No PharmGKB pharmacogenomic data curated for this drug.

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.

34 molecules share ≥1 primary target. Top 34 by shared-target count:

Molecule	Source	Status	Shared targets
DINOPROST	ChEMBL + PubChem	Phase 4 (approved)	PTGDR, PTGER1, PTGER2, PTGER3, PTGER4, PTGIR
dinoprostone	ChEMBL + PubChem	Phase 4 (approved)	PTGDR, PTGER1, PTGER2, PTGER3, PTGER4, PTGIR
RALINEPAG	ChEMBL	Phase 3	PTGDR, PTGER1, PTGER2, PTGER3, PTGER4, PTGIR
ILOPROST	ChEMBL + PubChem	Phase 4 (approved)	PTGDR, PTGER1, PTGER2, PTGER3, PTGIR
LAROPIPRANT	ChEMBL	Phase 4 (approved)	PTGDR, PTGER1, PTGER2, PTGER3, PTGIR
Grapiprant	ChEMBL + PubChem	Phase 2 (approved)	PTGER1, PTGER2, PTGER3, PTGER4, PTGIR
omidenepag isopropyl	ChEMBL + PubChem	Phase 4 (approved)	PTGER1, PTGER2, PTGER3, PTGER4
Cloprostenol	ChEMBL + PubChem	Phase 2 (approved)	PTGDR, PTGER1, PTGER2, PTGER3
Omidenepag	ChEMBL + PubChem	Phase 2 (approved)	PTGER1, PTGER2, PTGER3, PTGER4
Belzutifan	PubChem	Approved	PTGDR, PTGER2, PTGER3, PTGIR
Alprostadil	ChEMBL + PubChem	Phase 4 (approved)	PTGDR, PTGER2, PTGIR
SELEXIPAG	ChEMBL	Phase 4 (approved)	PTGDR, PTGIR
SETIPIPRANT	ChEMBL	Phase 3	PTGDR, PTGER2
TIMAPIPRANT	ChEMBL	Phase 3	PTGDR, PTGIR
BUTAPROST	ChEMBL	Phase 2	PTGER2, PTGIR
LASELIPAG	ChEMBL	Phase 2	PTGDR, PTGIR
PALUPIPRANT	ChEMBL	Phase 2	PTGER2, PTGER4
RAMATROBAN	ChEMBL	Phase 4 (approved)	PTGDR
ASAPIPRANT	ChEMBL	Phase 3	PTGDR
SEPETAPROST	ChEMBL	Phase 3	PTGER3
BGC-20-1531	ChEMBL	Phase 2	PTGER4
BGC-20-1531 FREE BASE	ChEMBL	Phase 2	PTGER4
BI-671800	ChEMBL	Phase 2	PTGDR
BMS-986310	ChEMBL	Phase 2	PTGER4
EVATANEPAG	ChEMBL	Phase 2	PTGER2
FLUPROSTENOL	ChEMBL	Phase 2	PTGER3
PINADOLINE	ChEMBL	Phase 2	PTGER2
TAPRENEPAG	ChEMBL	Phase 2	PTGER2
TAPRENEPAG ISOPROPYL	ChEMBL	Phase 2	PTGER2
VIDUPIPRANT	ChEMBL	Phase 2	PTGDR
epoprostenol	PubChem	Approved	PTGIR
Indomethacin	PubChem	Approved	PTGIR
Misoprostol	PubChem	Approved	PTGER2
Yohimbine	PubChem	Approved	PTGIR