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Compound Detail

CHEMBL3301604

RALINEPAG
🧪 Phase III
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🧪 Phase III
O=C(O)COC[C@H]1CC[C@H](COC(=O)N(c2ccccc2)c2ccc(Cl)cc2)CC1

Basic Information

ChEMBL ID CHEMBL3301604
Name RALINEPAG
Phase Phase III
Structure Type MOL
InChI Key NPDKXVKJRHPDQT-IYARVYRRSA-N

Known Names

APD-811 APD811 Ralinepag
9
Targets
15
Activities
3
Assay Types
30
PK Parameters
20
Publications
3
Known Names
1
Indications
1
Mechanisms

Molecular Properties

431.9
MW (Da)
5.52
ALogP
4
HBA
1
HBD
76.1
PSA (Ų)
0.59
QED
1
Ro5 Violations
8
Rot. Bonds

Drug Information

Molecule Type Small molecule
Chirality Single Enantiomer

Flags

Natural Product
USAN Stem -nepag
USAN Year 2014

Extended Properties

Molecular Formula C23H26ClNO5
MW 431.92
Aromatic Rings 2
Heavy Atoms 30
NP-Likeness -0.83

Mechanism of Action

Mechanism Action Type Target Direct Efficacy
Prostanoid IP receptor agonist AGONIST Prostacyclin receptor

Indications

Hypertension, Pulmonary

Activity Summary

Ki 9 meas. best 8.92
EC50 4 meas. best 8.57
IC50 2 meas. best 7.98

Target Activity Profile

Target Type Best pChEMBL Mean pChEMBL Best (nM) # Data
Unchecked
CHEMBL612545
Ki 8.92 7.755 1.2 2
Prostacyclin receptor
CHEMBL1995
EC50 8.57 8.32 2.7 2
Prostacyclin receptor
CHEMBL1995
Ki 8.52 8.52 3.0 1
Platelet
CHEMBL4296519
IC50 7.98 7.98 10.5 1
Prostacyclin receptor
CHEMBL1995
IC50 7.42 7.42 38.0 1
Prostacyclin receptor
CHEMBL3322
Ki 7.12 7.12 76.0 1
Prostaglandin E2 receptor EP3 subtype
CHEMBL3710
Ki 6.84 6.84 143.0 1
Prostacyclin receptor
CHEMBL3322
EC50 6.28 6.28 530.0 1
Prostaglandin E2 receptor EP2 subtype
CHEMBL1881
Ki 6.21 6.21 610.0 1
Prostaglandin E2 receptor EP4 subtype
CHEMBL1836
Ki 6.17 6.17 678.0 1
Prostaglandin D2 receptor
CHEMBL4427
EC50 6.07 6.07 850.0 1
Prostaglandin D2 receptor
CHEMBL4427
Ki 5.58 5.58 2600.0 1
Prostaglandin E2 receptor EP1 subtype
CHEMBL1811
Ki 5.02 5.02 9600.0 1

Pharmacokinetic Data

Parameter Value Units Species
AUC 14.6 ug.hr/kg Rattus norvegicus
AUC 2760.0 ng.hr.mL-1 Mus musculus
AUC 1050.0 ng.hr.mL-1 Canis lupus familiaris
AUC 145.0 ng.hr.mL-1 Macaca fascicularis
AUC 11500.0 ng.hr.mL-1 Mus musculus
AUC 719.0 ng.hr.mL-1 Canis lupus familiaris
AUC 9750.0 ng.hr.mL-1 Canis lupus familiaris
AUC 161.0 ng.hr.mL-1 Macaca fascicularis
AUC 2900.0 ng.hr.mL-1 Macaca fascicularis
AUC 5090.0 ng.hr.mL-1 Rattus norvegicus
CL 7.117 mL.min-1.kg-1 Rattus norvegicus
CL 11.48 mL.min-1.kg-1 Mus musculus
CL 3.367 mL.min-1.kg-1 Canis lupus familiaris
CL 14.68 mL.min-1.kg-1 Macaca fascicularis
Cmax 8566.4 nM Rattus norvegicus
Cmax 11437.3 nM Mus musculus
Cmax 757.08 nM Canis lupus familiaris
Cmax 7964.44 nM Canis lupus familiaris
Cmax 28.01 nM Macaca fascicularis
Cmax 214.85 nM Macaca fascicularis
F 57.0 % Rattus norvegicus
F 83.4 % Mus musculus
F 68.4 % Canis lupus familiaris
F 92.9 % Canis lupus familiaris
F 98.7 % Macaca fascicularis
F 100.0 % Macaca fascicularis
T1/2 1.0 hr Homo sapiens
T1/2 1.0 hr Rattus norvegicus
T1/2 6.7 hr Rattus norvegicus
T1/2 5.59 hr Mus musculus

Activity Data Samples

Top measurements by pChEMBL value

Target Type Rel. Value Units pChEMBL Assay PubMed
Unchecked Ki = 1.2 nM 8.92 Displacement of [3H]-iloprost from recombinant monkey IP receptor expressed in C... 28072531
Prostacyclin receptor EC50 = 2.7 nM 8.57 Agonist activity at human recombinant prostacyclin receptor expressed in CHO-K1 ... -
Prostacyclin receptor Ki = 3.0 nM 8.52 Displacement of [3H]-iloprost from recombinant human IP receptor expressed in CH... 28072531
Prostacyclin receptor EC50 = 8.5 nM 8.07 Agonist activity at recombinant human IP receptor expressed in CHO-K1 cells asse... 28072531
Platelet IC50 = 10.5 nM 7.98 Inhibition of ADP-induced platelet aggregation in human platelet rich plasma pre... -
Prostacyclin receptor IC50 = 38.0 nM 7.42 Agonist activity at IP receptor in human primary platelets assessed as inhibitio... 28072531
Prostacyclin receptor Ki = 76.0 nM 7.12 Displacement of [3H]-iloprost from recombinant rat IP receptor expressed in CHO-... 28072531
Prostaglandin E2 receptor EP3 subtype Ki = 143.0 nM 6.84 Displacement of [3H]-PGE2 from recombinant human EP3v6 receptor expressed in HEK... 28072531
Unchecked Ki = 256.0 nM 6.59 Displacement of [3H]-iloprost from recombinant dog IP receptor expressed in CHO-... 28072531
Prostacyclin receptor EC50 = 530.0 nM 6.28 Agonist activity at recombinant rat IP receptor expressed in CHO-K1 cells assess... 28072531
Prostaglandin E2 receptor EP2 subtype Ki = 610.0 nM 6.21 Displacement of [3H]-PGE2 from recombinant human EP2 receptor expressed in HEK29... 28072531
Prostaglandin E2 receptor EP4 subtype Ki = 678.0 nM 6.17 Displacement of [3H]-PGE2 from recombinant human EP4 receptor expressed in rat c... 28072531
Prostaglandin D2 receptor EC50 = 850.0 nM 6.07 Agonist activity at recombinant human DP1 receptor expressed in CHO-K1 cells ass... 28072531
Prostaglandin D2 receptor Ki = 2600.0 nM 5.58 Displacement of [3H]-PGD2 from recombinant human DP1 receptor 28072531
Prostaglandin E2 receptor EP1 subtype Ki = 9600.0 nM 5.02 Displacement of [3H]-PGE2 from recombinant human EP1 receptor expressed in HEK29... 28072531

Literature References

PubMed DOI Target Context # Activities
28072531 10.1021/acs.jmedchem.6b00871 Rattus norvegicus 14
28072531 10.1021/acs.jmedchem.6b00871 Cynomolgus monkey 14
28072531 10.1021/acs.jmedchem.6b00871 Canis familiaris 14
28072531 10.1021/acs.jmedchem.6b00871 Prostacyclin receptor 9
28072531 10.1021/acs.jmedchem.6b00871 Mus musculus 9
28072531 10.1021/acs.jmedchem.6b00871 ADMET 5
28072531 10.1021/acs.jmedchem.6b00871 Unchecked 5
28072531 10.1021/acs.jmedchem.6b00871 Plasma 4
28072531 10.1021/acs.jmedchem.6b00871 Prostaglandin D2 receptor 3
- 10.6019/CHEMBL4651402 SARS-CoV-2 2
28072531 10.1021/acs.jmedchem.6b00871 Prostaglandin E2 receptor EP4 subtype 2
28072531 10.1021/acs.jmedchem.6b00871 Prostaglandin E2 receptor EP3 subtype 2
28072531 10.1021/acs.jmedchem.6b00871 Prostaglandin E2 receptor EP2 subtype 2
28072531 10.1021/acs.jmedchem.6b00871 Cytochrome P450 2D6 1
28072531 10.1021/acs.jmedchem.6b00871 Cytochrome P450 3A4 1
28072531 10.1021/acs.jmedchem.6b00871 Cytochrome P450 2C8 1
28072531 10.1021/acs.jmedchem.6b00871 Cytochrome P450 2C9 1
28072531 10.1021/acs.jmedchem.6b00871 Cytochrome P450 2C19 1
33314936 10.1021/acs.jmedchem.0c01093 ADMET 1
28072531 10.1021/acs.jmedchem.6b00871 Cytochrome P450 1A2 1

Data from ChEMBL 36 via Core Engine