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Details

Stereochemistry ABSOLUTE
Molecular Formula C23H34O5
Molecular Weight 390.5131
Optical Activity UNSPECIFIED
Defined Stereocenters 5 / 5
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of TREPROSTINIL

SMILES

[H][C@]12C[C@@H](O)[C@H](CC[C@@H](O)CCCCC)[C@@]1([H])CC3=C(C2)C(OCC(O)=O)=CC=C3

InChI

InChIKey=PAJMKGZZBBTTOY-ZFORQUDYSA-N
InChI=1S/C23H34O5/c1-2-3-4-7-17(24)9-10-18-19-11-15-6-5-8-22(28-14-23(26)27)20(15)12-16(19)13-21(18)25/h5-6,8,16-19,21,24-25H,2-4,7,9-14H2,1H3,(H,26,27)/t16-,17-,18+,19-,21+/m0/s1

HIDE SMILES / InChI

Description

Treprostinil (marketed under the trade names Remodulin for infusion) is a vasodilator that is used for the treatment of pulmonary arterial hypertension. Pulmonary arterial hypertension (PAH) is a disease in which blood pressure is abnormally high in the arteries between the heart and lungs. PAH is characterized by symptoms of shortness of breath during physical exertion. The condition can ultimately lead to heart failure. Treprostinil is a potent oral antiplatelet agent. The major pharmacologic actions of treprostinil are direct vasodilation of pulmonary and systemic arterial vascular beds and inhibition of platelet aggregation. In animals, the vasodilatory effects reduce right and left ventricular afterload and increase cardiac output and stroke volume. Other studies have shown that treprostinil causes a dose-related negative inotropic and lusitropic effect. No major effects on cardiac conduction have been observed. Treprostinil had high affinity for the Prostaglandin D2 receptor (DP1), Prostaglandin E2 receptor EP2 subtype (EP2) and Prostaglandin D2 receptor (IP) receptors (Ki 4.4, 3.6 and 32 nM, respectively), low affinity for EP1 and EP4 receptors and even lower affinity for EP3, Prostaglandin F (FP) and thromboxane (TP) receptors. Treprostinil has demonstrated a unique effect on PPAR gamma, a transcription factor important in vascular pathogenesis as a mediator of proliferation, inflammation and apoptosis. Through a complementary, yet cyclic AMP-independent pathway, treprostinil activates PPARs, another mechanism that contributes to the anti-growth benefits of the prostacyclin class.

Originator

Approval Year

Targets

Primary TargetPharmacologyConditionPotency
32.0 nM [Ki]
4.4 nM [Ki]
3.6 nM [Ki]

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
REMODULIN

Cmax

ValueDoseCo-administeredAnalytePopulation
0.71 ng/mL
0.5 mg 3 times / day multiple, oral
TREPROSTINIL plasma
Homo sapiens
0.54 ng/mL
0.5 mg single, oral
TREPROSTINIL plasma
Homo sapiens

AUC

ValueDoseCo-administeredAnalytePopulation
6.53 ng × h/mL
0.5 mg 3 times / day multiple, oral
TREPROSTINIL plasma
Homo sapiens
2.46 ng × h/mL
0.5 mg single, oral
TREPROSTINIL plasma
Homo sapiens

T1/2

ValueDoseCo-administeredAnalytePopulation
1.34 h
0.5 mg 3 times / day multiple, oral
TREPROSTINIL plasma
Homo sapiens
1.06 h
0.5 mg single, oral
TREPROSTINIL plasma
Homo sapiens

Funbound

ValueDoseCo-administeredAnalytePopulation
9%
TREPROSTINIL plasma
Homo sapiens

Doses

AEs

Drug as perpetrator​

Drug as victim

Tox targets

PubMed

Sample Use Guides

In Vivo Use Guide
1.25 ng/kg/min (initial dose for continuous infusion, dosage should be chronically adjusted depending on clinical response)
Route of Administration: Other
In Vitro Use Guide
Treprostinil (0.15 - 15 ng/ml) rat cardiomyocytes