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. 2009 Jul 15;158(1):104–145. doi: 10.1111/j.1476-5381.2009.00317.x

Table 2.

Affinities of prostanoid receptor antagonists in functional isolated preparations

Antagonist Species Tissue system Agonist pA2 Reference
DP1 receptor
AH-6809 Human Neutrophil/superoxide release BW-245C 6.55 Wheeldon and Vardey (1993)
BW-245C 6.59 Lydford et al. (1996a)
Platelet/aggregation PGD2 6.27a Keery and Lumley (1988)
Cow Embryonic tracheal fibroblast/cAMP PGD2 6.36 Ito et al. (1990)
Rabbit Saphenous vein BW-245C 5.93 Lydford et al. (1996c)
BW-A868C Human Neutrophil/superoxide release BW-245C 9.46 Lydford et al. (1996a)
Platelet/aggregation BW-245C 9.26 Giles et al. (1989)
Pulmonary vein PGD2 7.84 Walch et al. (1999)
Uterus (non-pregnant) BW-245C 8.3 Senior et al. (1992)
Uterus (pregnant) BW-245C 8.6 Senior et al. (1993)
Cow Embryonic tracheal fibroblast/cAMP BW-245C 8.0 Crider et al. (1999)
Dog Nasal vein BW-245C 7.3 Liu et al. (1996a)
Tracheal epithelium/Cl- secretion BW-245C 8.16 Liu et al. (1996b)
Rabbit Jugular vein BW-245C 8.73 Giles et al. (1989)
Saphenous vein BW-245C 8.50 Lydford et al. (1996c)
MK-0524 (Laropiprant) Human rc-DP1/HEK-293E/binding [3H]-PGD2 10.5b Sturino et al. (2007)
Platelet/cAMP PGD2 10.05c Sturino et al. (2007)
ONO-AE3-237 Human rc-DP1/CHO/binding [3H]-PGD2 7.74 Torisu et al. (2004c)
S-5751 Human Platelet/cAMP PGD2 9.02b,c Arimura et al. (2001)
Guinea pig Platelet/cAMP PGD2 7.50b,c Arimura et al. (2001)
ZK-138357 Human Neutrophil/superoxide release BW-245C 7.25 Lydford et al. (1996a)
Rabbit Saphenous vein BW-245C 5.05 Lydford et al. (1996a)
Rat Peritoneal mast cell BW-245C ∼6.0 Chan et al. (2000)
Compound 1 Human Platelet/binding [3H]-PGD2 6.22 Mitsumori et al. (2003a)
Compound 2 Human Platelet/binding [3H]-PGD2 7.62 Mitsumori et al. (2003a)
Compound 3 Human rc-DP1/HEK-293-Gα15/Ca2+ BW-245C [∼7.4] Krauss et al. (2005)
Compound 4 Human rc-DP1/CHO/binding [3H]-PGD2 8.27 Torisu et al. (2004c)
Compound 5 Human rc-DP1/HEK-293/binding [3H]-PGD2 9.0 Beaulieu et al. (2008)
DP2 receptor
BAY-u3405 (Ramatroban) Human rc-DP2/CHO/GTPγS binding PGD2 7.44 Mathiesen et al. (2006)
Eosinophil/shape change PGD2 ∼8.0a Mathiesen et al. (2006)
K-117 Human rc-DP2/HEK-293/binding [3H]-PGD2 8.26 Mimura et al. (2005)
K-604 Human rc-DP2/HEK-293/binding [3H]-PGD2 7.96 Mimura et al. (2005)
TM-30089d (CAY-10471) Human rc-DP2/HEK-293/binding [3H]-PGD2 8.74 Mathiesen et al. (2006)
9.22 Ulven and Kostenis (2005)
Compound 6 Human rc-DP2/pre-B L1.2/Ca2+ PGD2 [6.8] Bauer et al. (2002)
Compound 7 Human rc-DP2/HEK-293/binding [3H]-PGD2 8.64c Birkinshaw et al. (2006)
Compound 8 Human rc-DP2/HEK-293/binding [3H]-PGD2 [9.40]c Bonnert and Rasul (2004)
Compound 9 Human rc-DP2/CHO/binding [3H]-PGD2 7.17 Armer et al. (2005)
Eosinophil/shape change PGD2 7.13c Armer et al. (2005)
Th2-lymphocyte/chemotaxis PGD2 7.17c Armer et al. (2005)
Compound 10 Human rc-DP2/CHO/Ca2+ PGD2 [8.53] Fretz et al. (2005)
Compound 11 Human rc-DP2/HEK-293/binding [3H]-PGD2 [9.0] Bonnert et al. (2005c)
EP1 receptor
AH-6809 Human rc-EP1/HEK-293E/reporter gene Iloprost ∼6.4 Durocher et al. (2000)
Pulmonary vein Sulprostone 5.52 Walch et al. (2001)
Guinea pig Ileum PGE2 6.8 Coleman et al. (1987)
Ileum PGE2 7.39 Eglen and Whiting (1988)
Ileum PGE1 7.42 Eglen and Whiting (1988)
Ileum 16,16-DM PGE2 7.59 Eglen and Whiting (1988)
Trachea 16,16-DM PGE2 7.48 Eglen and Whiting (1988)
Trachea 17-Phenyl PGE2 7.35 Lawrence et al. (1992)
GW-848687 Human rc-EP1/not given/reporter gene PGE2 9.1 Giblin et al. (2007)
MF-266-1 Human rc-EP1/HEK-293/Ca2+ PGE2 7.8 Clark et al. (2008)
ONO-8711 Mouse rc-EP1/CHO/binding [3H]-PGE2 8.77 Watanabe et al. (1999)
Human rc-EP1/CHO/binding [3H]-PGE2 9.22 Watanabe et al. (1999)
ONO-8713 Mouse rc-EP1/not given/binding [3H]-PGE2 9.5 Narumiya and Fitzgerald (2001)
SC-19220 Guinea pig Ileum PGE2 5.5 Sanner (1969)
Ileum PGE2 5.6 Bennett and Posner (1971)
Trachea PGF2α 6.6 Farmer et al. (1974)
SC-51089 Human rc-EP1/HEK-293E/reporter gene Iloprost 6.94 Durocher et al. (2000)
Guinea pig Ileum PGE2 6.5 Hallinan et al. (1993)
Ileum PGE2 6.7 Sametz et al. (2000)
SC-51322 Human rc-EP1/HEK-293E/reporter gene Iloprost 8.80 Durocher et al. (2000)
Guinea pig Ileum PGE2 8.1 Hallinan et al. (1994)
Trachea 17-Phenyl PGE2 8.45 Hung et al. (2006)
Compound 13 Mouse rc-EP1/CHO/Ca2+ PGE2 8.25c Naganawa et al. (2006)
Compound 14 Human rc-EP1/HEK-293E/binding [3H]-PGE2 8.0 Ruel et al. (1999)
Compound 15 Human rc- EP1/CHO/Ca2+ PGE2 8.2 Hall et al. (2007b)
EP2 receptor
AH-6809 Human rc-EP2/COS-7/cAMP PGE2 ∼6.5 Woodward et al. (1995)
Bronchus PGE2 5.78 Norel et al. (1999)
Guinea pig Trachea PGE2 5.7e KJ Ong and RL Jones (unpublished)
EP3 receptor
DG-041 Human rc-EP3/Chem-1/Ca2+ PGE2 8.09c Singh et al. (2009)
L-798106 Guinea pig Aorta 17-Phenyl PGE2f 7.96 Jones et al. (2008)
Trachea Sulprostone 7.82 Clarke et al. (2004)
Vas deferens Sulprostone 7.48 Clarke et al. (2004)
L-826266 Human rc-EP3/HEK-293E/Ca2+ PGE2 7.97 R.L. Jones et al. (2008, submitted)
Erythroleukaemia cell/cAMP Sulprostone 8.35 Clark et al. (2008)
Guinea pig Aorta 17-Phenyl PGE2 7.58 R.L. Jones et al. (2008, submitted)
ONO-AE3-240 Mouse rc-EP3/not given/Ca2+ PGE2 8.8 Amano et al. (2003)
Compound 17 Human Erythroleukaemia cell/cAMP Sulprostone 6.89 Gallant et al. (2002)
Compound 18 Human rc-EP3/HEK-293E/binding [3H]-PGE2 7.7 Juteau et al. (2001)
Compound 19 Human rc-EP3/HEK-293E/cAMP PGE2 8.22 Belley et al. (2005)
EP4 receptor
AH-23848 Sheep Ductus arteriosus PGE2 ∼5.2a Bouayad et al. (2001)
Human Middle cerebral artery PGE2 5.7 Davis et al. (2004)
Pig Saphenous vein PGE2 5.0 Coleman et al. (1994a)
Rabbit Saphenous vein PGE2 4.96 Lydford et al. (1996b)
Mouse rc-EP4/CHO/cAMP PGE2 5.3 Nishigaki et al. (1995)
BGC-20-1531 Human rc-EP4/HEK-293E/cAMP PGE2 7.6 Maubach et al. (2009)
Middle cerebral artery PGE2 7.8 Maubach et al. (2009)
Dog Middle meningeal artery PGE2 7.7 Maubach et al. (2009)
CJ-023423 Human rc-EP4/HEK-293/cAMP PGE2 8.3 Nakao et al. (2007)
Rat rc-EP4/HEK-293/cAMP PGE2 8.2 Nakao et al. (2007)
CJ-042794 Human rc-EP4/HEK-293/cAMP PGE2 8.6 Murase et al. (2008b)
Rat rc-EP4/HEK-293/cAMP PGE2 8.7 Murase et al. (2008a)
GW-627368 Human rc-EP4/HEK-293/cAMP PGE2b 7.9 Wilson et al. (2006)
Pulmonary vein ONO-AE1-329 7.06 Foudi et al. (2008)
Pig Saphenous vein PGE2 9.2 Wilson et al. (2006)
Rabbit Saphenous vein PGE2g ≥8.5 Jones and Chan. (2005)
L-161982 Human rc-EP4/HEK-293/cAMP PGE2 ∼8.5 Machwate et al. (2001)
BEAS-2B cell/CRE reporter ONO-AE1-329 9.14 L.M. Ayer and M.A. Giembycz (unpublished)
Middle cerebral artery PGE2 8.4 Davis et al. (2004)
Rat rc-EP4/HEK-293/binding [3H]-PGE2 7.50 Machwate et al. (2001)
Periosteal cell/cAMP PGE2 7.0c Machwate et al. (2001)
MF-498 Human rc-EP4/HEK-293/cAMP PGE2 8.77c Clark et al. (2008)
ONO-AE2-227 Mouse rc-EP4/CHO/cAMP PGE2 8.0c Mutoh et al. (2002)
ONO-AE3-208 Mouse rc-EP4/not given/binding [3H]-PGE2 8.89 Kabashima et al. (2002)
Compound 20 Human rc-EP4/HEK-293E/cAMP PGE2 8.49c Burch et al. (2008)
FP receptor
AS-604872 Human rc-FP/HEK-293E/PI PGF2α 7.33c Cirillo et al. (2007)
THG-113 Pig Retinal blood vessel PGF2α [6.34]c Peri et al. (2006)
THG-113.31 Pig Retinal blood vessel PGF2α [8.00]c Peri et al. (2006)
THG-113.824 Pig Retinal blood vessel PGF2α [8.96]c Peri et al. (2006)
THG-113.825 Pig Retinal blood vessel PGF2α 7.21c Peri et al. (2006)
Prostamide F receptor
AGN-204396 Cat Iris sphincter Prostamide F2α 5.64 Woodward et al. (2007)
IP receptor
RO-1138452 Human rc-IP/CHO/cAMP Carbacyclin 9.0 Bley et al. (2006)
Pulmonary artery Cicaprost 8.20 Jones et al. (2006)
Guinea pig Aorta Cicaprost 8.39 Jones et al. (2006)
Rabbit Mesenteric artery Cicaprost 8.12 Jones et al. (2006)
RO-3244794 Human rc-IP/CHO/cAMP Carbacyclin 8.5 Bley et al. (2006)
BEAS-2B cell/CRE reporter Taprostene 9.24 L.A. Ayer and M.A. Giembycz (unpublished)
Compound 21 Rat rc-IP/not given/cAMP (Not given) [8.12]h Keitz et al. (2004)
Compound 22 Rat UMR-106 osteosarcoma cell/cAMP Iloprost 6.41 Nakae et al. (2005)
Compound 23 Rat UMR-106 osteosarcoma cell/cAMP Iloprost 6.32 Nakae et al. (2005)
Compound 24 Human Platelet membrane/cAMP Iloprost 7.8c Brescia et al. (2007)
TP receptor
AA-2414 (Seratrodast) Human Bronchus U-46619 7.7 Itoh et al. (1993)
Pig Coronary artery U-44069 9.0 Imura et al. (1990)
Guinea pig Aorta U-46619 8.5 Zhang et al. (1996)
Trachea U-46619 7.69 Ashida et al. (1989)
Rat Aorta U-46619 7.8 Zhang et al. (1996)
AH-23848 Human Bronchus U-46619 8.5 Coleman and Sheldrick (1989)
Bronchus U-46619 6.9 McKenniff et al. (1988)
Hand vein U-46619 8.4 Arner et al. (1991)
Lung parenchyma U-46619 8.7 McKenniff et al. (1988)
Platelet/aggregation U-46619 8.05 Tymkewycz et al. (1991)
Guinea pig Lung parenchyma U-46619 8.7 McKenniff et al. (1988)
Trachea U-46619 8.7 McKenniff et al. (1988)
Trachea U-46619 9.76 Tymkewycz et al. (1991)
Rat Aorta U-46619 8.47 Tymkewycz et al. (1991)
Lung parenchyma U-46619 6.9 Norman et al. (1992)
Platelet/aggregation U-46619 8.19 Tymkewycz et al. (1991)
BAY-u3405 (Ramatroban) Human Bronchus U-46619 8.8 McKenniff et al. (1991)
Pulmonary vein U-46619 8.94 Walch et al. (2001)
Guinea pig Lung parenchyma U-46619 7.7 Norman et al. (1992)
Trachea U-46619 8.7 McKenniff et al. (1991)
Rat Lung parenchyma U-46619 8.6 McKenniff et al. (1991)
BM-13177 (Sulotroban) Human Platelet/aggregation U-46619 6.31 Karasawa et al. (1991a)
Guinea pig Aorta U-46619 5.58 Karasawa et al. (1991b)
Rabbit Jugular vein U-46619 6.01 Giles et al. (1989)
BM-13505 Human Hand vein U-46619 7.9 Arner et al. (1991)
Platelet/aggregation U-46619 7.75 Karasawa et al. (1991a)
Uterus (non-pregnant) U-46619 7.4 Senchyna and Crankshaw (1996)
Guinea pig Aorta U-46619 6.89 Dubéet al. (1992)
Aorta U-46619 7.22 Karasawa et al. (1991b)
Aorta U-46619 7.3 Zhang et al. (1996)
Lung parenchyma U-46619 7.0 Norman et al. (1992)
Trachea U-46619 7.73 Dubéet al. (1992)
Trachea U-46619 7.5 Ogletree and Allen (1992)
Rat Aorta U-46619 8.2 Zhang et al. (1996)
Aorta U-46619 8.6 Ogletree and Allen (1992)
Lung parenchyma U-46619 7.5 Norman et al. (1992)
BMS-180291 (Ifetroban) Human Platelet membrane/binding [3H]-SQ-29548 8.4 Ogletree et al. (1993)
Guinea pig Aorta U-46619 9.8 Zhang et al. (1996)
Rat Aorta U-46619 9.5 Zhang et al. (1996)
CV-4151 Human Platelet/aggregation U-46619 5.2 Watts et al. (1991)
Rabbit Aorta U-44069 5.9 Imura et al. (1988)
EP-092 Human Bronchus U-46619 7.37 Featherstone et al. (1990)
Bronchus U-46619 6.8 McKenniff et al. (1988)
Lung parenchyma U-46619 8.9 McKenniff et al. (1988)
Platelet /aggregation U-46619 7.73 Tymkewycz et al. (1991)
Uterine artery U-46619 8.5 Baxter et al. (1995)
Guinea pig Lung parenchyma U-46619 8.7 McKenniff et al. (1988)
Trachea U-46619 7.29 Featherstone et al. (1990)
Trachea U-46619 8.7 McKenniff et al. (1988)
Trachea U-46619 8.02 Tymkewycz et al. (1991)
Rat Aorta U-46619 8.55 Tymkewycz et al. (1991)
Lung parenchyma U-46619 7.1 Norman et al. (1992)
Platelet aggregation U-46619 7.80 Tymkewycz et al. (1991)
EP-169 Human Platelet/aggregation U-46619 8.30 Tymkewycz et al. (1991)
Pulmonary artery U-46619 ∼8.2 Qian et al. (1994)
Guinea pig Trachea U-46619 8.77 Tymkewycz et al. (1991)
Rat Aorta U-46619 8.73 Tymkewycz et al. (1991)
Platelet/aggregation U-46619 8.48 Tymkewycz et al. (1991)
Glibenclamide Human Internal mammary artery U-46619 6.3i Stanke et al. (1998)
Saphenous vein 6.7i Stanke et al. (1998)
Dog Coronary artery U-46619 6.2 Cocks et al. (1990)
Rabbit Aorta U-46619 6.08a Pfister et al. (2004)
Guinea pig Aorta U-46619 <5.0 Kemp and McPherson (1998)
Rat Aorta U-46619 6.13 Kemp and McPherson (1998)
GR-32191 (Vapiprost) Human Bladder (detrusor) U-46619 8.27 Palea et al. (1998)
Bronchus U-46619 8.77 Featherstone et al. (1990)
Bronchus U-46619 8.40 Armour et al. (1989)
Platelet/binding [3H]-GR-32191 8.66 Armstrong et al. (1993)
Pulmonary artery U-46619 8.18 Lumley et al. (1989)
Saphenous vein U-46619 8.93 Furci et al. (1991)
Umbilical artery U-46619 8.0 Boersma et al. (1999)
Uterine artery U-46619 8.5 Baxter et al. (1995)
Uterus (non-pregnant) U-46619 8.6 Senchyna and Crankshaw (1996)
Uterus (pregnant) U-46619 8.5a Senior et al. (1993)
Guinea pig Aorta U-46619 8.77 Lumley et al. (1989)
Aorta U-46619 9.4 Ogletree and Allen (1992)
Trachea U-46619 8.26 Featherstone et al. (1990)
Trachea U-46619 9.43 Tymkewycz et al. (1991)
Trachea U-46619 10.0 Ogletree and Allen (1992)
Rat Aorta U-46619 7.87 Lumley et al. (1989)
Aorta U-46619 7.49 Furci et al. (1991)
Aorta U-46619 8.41 Tymkewycz et al. (1991)
Aorta U-46619 8.3 Ogletree and Allen (1992)
Trachea U-46619 8.31 Lydford and McKechnie (1994)
GR-83783j Rat Aorta U-46619 7.5 Campbell et al. (1991a)
GR-108774j Rat Aorta U-46619 9.2 Campbell et al. (1991b)
ICI-192605 Human Platelet/aggregation U-46619 8.16 Brewster et al. (1988)
Umbilical artery U-46619 8.1 Boersma et al. (1999)
Umbilical vein U-46619 9.07 Daray et al. (2003)
Uterus (non-pregnant) U-46619 9.2 Senchyna and Crankshaw (1996)
Rat Aorta U-46619 8.4 Brewster et al. (1988)
I-PTA-OH Guinea pig Lung parenchyma U-46619 5.6 Norman et al. (1992)
Rat Lung parenchyma U-46619 5.8 Norman et al. (1992)
I-SAP Human Platelet/aggregation U-46619 8.01k Naka et al. (1992)
KW-3635 Human Platelet/aggregation U-46619 8.88 Karasawa et al. (1991a)
Guinea pig Aorta U-46619 7.74 Karasawa et al. (1991b)
L-655240 Guinea pig Aorta U-44069 8.0 Hall et al. (1987)
Aorta U-44069 8.0 Hall et al. (1987)
ONO-11120 Human Platelet/binding [125I]-PTA-0H 7.71c Narumiya et al. (1986)
Platelet/aggregation U-46619 7.49 Tymkewycz et al. (1991)
Guinea pig Trachea U-46619 8.07 Tymkewycz et al. (1991)
Rat Aorta U-46619 7.14 Tymkewycz et al. (1991)
Platelet/aggregation U-46619 7.38 Tymkewycz et al. (1991)
ONO-NT-126 Human Astrocytoma cell/PI STA2 10.0 Nakahata et al. (1990)
Ridogrelj Human Platelet/aggregation U-46619 5.7 Watts et al. (1991)
Rat Tail artery U-46619 5.5 Janssens et al. (1990)
(±)-S-145 (Domitroban)l Human Astrocytoma cell/PI STA2 8.48 Nakahata et al. (1990)
Platelet membrane/binding [3H]-(+)-S-145 9.35 Kishino et al. (1991)
Rat Aorta smooth muscle cell/binding [3H]-SQ-29548 9.5a Hanasaki et al. (1988)
S-18886 (Terutroban) Rabbit Saphenous vein U-46619 8.9 Cimetière et al. (1998)
SQ-29548 Human Astrocytoma cell/PI STA2 8.08 Nakahata et al. (1990)
Immortalized ciliary epithelial cell/PI U-46619 7.7m Sharif et al. (2002)
Corpus cavernosum U-46619 9.0 Angulo et al. (2002)
Umbilical artery U-46619 7.6 Boersma et al. (1999)
Umbilical vein U-46619 7.96 Daray et al. (2003)
Uterus (non-pregnant) U-46619 8.2 Senchyna and Crankshaw (1996)
Pig Coronary artery U-46619 8.8a Kromer and Tippins (1996)
Rabbit Aorta U-46619 7.95 Yoshida et al. (2007)
Guinea pig Aorta U-46619 7.96 Dubéet al. (1992)
Aorta U-46619 8.9 Ogletree and Allen (1992)
Aorta U-46619 8.5 Zhang et al. (1996)
Lung parenchyma U-46619 7.7 Norman et al. (1992)
Trachea U-46619 8.70 Dubéet al. (1992)
Trachea U-46619 8.9 Ogletree and Allen (1992)
Rat Aorta U-46619 9.2 Zhang et al. (1996)
Lung parenchyma U-46619 7.2 Norman et al. (1992)
SQ-30741 Human Coronary artery U-46619 7.54 Maassen VanDenBrink et al., 1996)
Human Umbilical artery U-46619 7.0 Boersma et al. (1999)
Guinea pig Aorta U-46619 8.1 Ogletree and Allen (1992)
Trachea U-46619 8.6 Ogletree and Allen (1992)
Rat Aorta U-46619 7.9 Ogletree and Allen (1992)
YM-158 Guinea pig Trachea U-46619 8.81n Arakida et al. (1998)
Z-335 Human Platelet membrane/binding [3H]-SQ-29548 7.52 Tanaka et al. (1998)
Platelet/shape changeo U-46619 8.02 Yoshida et al. (2007)
Rabbit Aorta U-46619 8.64 Yoshida et al. (2007)
ZD-1542j Guinea pig Lung parenchyma U-46619 8.5 Brownlie et al. (1993)
Trachea U-46619 8.3 Brownlie et al. (1993)
Rat Aorta U-46619 8.51 Brownlie et al. (1993)

pA2 values relate to functional assays. Recombinant (rc-) systems: prostanoid receptor followed by the carrier cell line and second messenger measurement. Smooth muscle preparations: contraction or relaxation of induced tone. Platelets: all data from plasma-free platelet suspensions. Where pA2 values are not available, pKi/pKD values derived from radioligand binding are given (italics). Affinity values in square brackets derive from the patent literature.

Structures of compounds: 1–5, Figure 1; 6–12, Figure 2; 13–15, Figure 3; 16–19, Figure 4; 20, Figure 5; 21–24, Figure 7.

BEAS, human bronchial epithelium; CHO, Chinese hamster ovary; COS-7, African green monkey kidney; HEK, human embryonic kidney; CRE, cAMP response element; 16,16-DM PGE2, 16,16-dimethyl PGE2; PI, phosphoinositide.

a

Our calculation.

b

Appreciable affinity for corresponding TP receptor.

c

pIC50.

d

Insurmountable antagonism in functional DP2 systems.

e

1 µM SC-51322 present.

f

Replacement for sulprostone, which had slow onset and offset.

g

Possible interference by EP2 system.

h

pKi.

i

pKb for non-competitive antagonism.

j

Combined TP antagonist/TXS inhibitor.

k

Shape change seen.

l

Data for (+)- and (−)-enantiomers in Kishino et al. (1991).

m

Non-competitive antagonism.

n

pA2= 8.87 for LTD4 antagonism.

o

Suppression of maximum aggregation response.