Table 1

Summary of all functional and affinity data, normalized relative to PGE₂ as described under Materials and Methods

Compound	Compound	Trivial Name	Log₁₀ relative aequorin ± SD (n = 3)	EC₅₀ cmpd/EC₅₀ PGE₂	Log₁₀ relative binding (n = 2)		K_i (cmpd)/ K_i(PGE₂)
(5Z,11α,13E,15S) -11,15-Dihydroxy-9-methylene-prosta-5,13-dien-1-oic acid	1	9-Deoxy-9-methylene-prostaglandin E₂	−0.53 ± 0.11	0.30	−0.23	−0.03	0.75
[3a,S-[2E,3α,4α(1E,3R^*) ,5β,6α]]-5-[Hexahydro-5-hydroxy-4-(3-hydroxy-1-octenyl)-2(1H)-pentalenylidene]-pentanoic acid	2	Carbacyclin (carbaprostacyclin)	−0.20 ± 0.09	0.63	0.23	0.26	1.8
5-[Hexahydro-5-hydroxy-4-(3-hydroxy-4-methyl-1-octen-6-ynyl)-2(1H)-pentalenylidene]pentanoic acid	3	Iloprost	−0.18 ± 0.05	0.66	−0.05	0.03	0.98
(5Z,11α,13E,15R) -11,15-Dihydroxy-16,16-dimethyl-9-oxoprosta-5,13-dien-1-oic acid	4	16,16-Dimethyl-prostaglandin E₂	−0.16 ± 0.02	0.69	−0.82	−0.85	0.15
[1R-[1α(Z),2β(1E,3S^*) ,3α]]-7-[3-Hydroxy-2-(3-hydroxy-5-phenyl-1-pentenyl)-5-oxocyclopentyl]-5-heptenoic acid	5	17-Phenyl-ω-trinor-prostaglandin E₂	−0.15 ± 0.02	0.71	0.04	−0.77	0.43
[1α(Z),2β(1E,3R^*),3α,5α] (±)-7-[3,5-Dihydroxy-2-(3-hydroxy-4-phenoxy-1-butenyl)cyclopentyl]-5-heptenoic acid	6	16-Phenoxy-ω-tetranor-prostaglandin F_2α	−0.05 ± 0.08	0.88	0.04	0.43	1.7
[1R-[1α(Z),2β(1E,3S^*) ,3α,5α]]-7-[3,5-Dihydroxy-2-(3-hydroxy-5-phenyl-1-pentenyl)cyclopentyl]-5-heptenoic acid	7	17-Phenyl-ω-trinor-prostaglandin F_2α	−0.04 ± 0.14	0.92	0.61	0.85	5.4
(5Z,11α,13E,15S) -11,15-Dihydroxy-9-oxoprosta-5,13-dien-1-oic acid	8	Prostaglandin E₂		1			1
(5Z,11α,13E,15S,17Z) -11,15-Dihydroxy-9-oxoprosta-5,13,17-trien-1-oic acid	9	Prostaglandin E₃	0.11 ± 0.10	1.3	0.86	0.95	8.0
(5Z,13E,15R) -15-Hydroxy-16,16-dimethyl-9-oxoprosta-5,13-dien-1-oic acid	10	11-Deoxy-16,16-dimethyl-prostaglandin E₂	0.26 ± 0.05	1.8	0.60	0.57	3.8
(11α,15S) -11,15-Dihydroxy-9-oxoprost-1-oic acid	11	13,14-Dihydro-prostaglandin E₁(PGE₀)	0.36 ± 0.16	2.3	1.07	1.51	20
(5Z,11α,13E,15S) -11,15-Dihydroxy-15-methyl-9-oxoprosta-5,13-dien-1-oic acid	12	15(S) -15-Methyl-prostaglandin E₂	0.38 ± 0.15	2.4	0.77	0.85	6.5
[1R-[1α(Z),2β(1E,3R^*) ,3α]]-7-[3-Hydroxy-2-(3-hydroxy-4-phenoxy-1-butenyl)-5-oxocyclopentyl]- N -(methylsulfonyl)-5-heptenamide	13	Sulprostone	0.48 ± 0.13	3.0	1.16	1.24	16
(11α,13E,15S) -11,15-Dihydroxy-9-oxoprost-13-en-1-oic acid	14	Prostaglandin E₁	0.50 ± 0.14	3.2	1.12	0.97	11
(5Z,9α,11α,13E,15S) -9,11,15-Trihydroxyprosta-5,13-dien-1-oic acid	15	Prostaglandin F_2α	1.00 ± 0.04	10	1.39	1.77	38
(5Z,9β,11α,13E,15S) -9,11,15-Trihydroxyprosta-5,13-dien-1-oic acid	16	9β-11α-Prostaglandin F₂	1.01 ± 0.11	10	2.00	1.64	66
(5Z,9β,11α,13E,15S) -11,15-Dihydroxy-9-chloro-15-cyclohexyl-ω-pentanor-prosta-5,13-dien-1-oic acid	17	ZK110841	1.10 ± 0.06	13	−0.45	−0.59	0.30
[1α,2β (1E,3R^*), 3α]-7-[3-Hydroxy-2-(3-hydroxy-4-phenoxy-1-butenyl)-5-oxocyclopentyl]-4,5-heptadienoic acid methyl ester	18	Enprostil	1.10 ± 0.03	13	0.57	0.71	4.4
[1R-[1α(Z),2β(1E,3S^*), 3α,5α]]-7-[2-(3-Cyclohexyl-3-hydroxy-1-propenyl)-3,5-dihydroxycyclopentyl]-5-heptenoic acid	19	15-Cyclohexyl-pentanor-prostaglandin F_2α	1.19 ± 0.20	15	1.87	2.01	87
(13E,15S) -15-Hydroxy-9-oxo-16-phenoxy-ω-tetranorprost-13-en-1-oic acid	20	M&B 28767	1.21 ± 0.01	16	1.63	1.72	48
(5Z,9α,11α,13E,15S) -9,11,15-Trihydroxy-15-methyl-prosta-5,13-dien-1-oic acid	21	15(S) -15-Methyl-prostaglandin F_2α(Carboprost)	1.43 ± 0.07	27	2.15	2.25	160
[1R-[1α(Z),2β(1E,3R^*),3α,5α]] -7-[2-[4-(3-Chlorophenoxy)-3-hydroxy-1-butenyl]-3,5-dihydroxycyclopentyl]-5-heptenoic acid	22	Cloprostenol	1.51 ± 0.04	32	1.79	1.84	65
[1R-[1α(Z),2β(R^*), 3α,5α]]-7-[3,5-Dihydroxy-2-(3-hydroxy-5-phenylpentyl)cyclopentyl]-5-heptenoic acid	23	Latanoprost free acid	1.61 ± 0.09	41	1.90	2.23	120
(5Z,13E,15S) -15-Hydroxy-9-oxoprosta-5,13-dien-1-oic acid	24	11-Deoxy-prostaglandin E₂	1.64 ± 0.04	43	2.00	2.15	120
(5Z,8β,11α,13E,15S) -11,15-Dihydroxy-9-oxoprosta-5,13-dien-1-oic acid	25	8-iso-Prostaglandin E₂	1.73 ± 0.05	53	2.14	1.99	120
(5Z,11β,13E,15S) -11,15-Dihydroxy-9-oxoprosta-5,13-dien-1-oic acid	26	11β-Prostaglandin E₂	1.78 ± 0.07	61	2.28	2.29	190
(5Z,9α,11α,13E,15S) -9,11,15-Trihydroxy-6-oxo-prosta-5,13-dien-1-oic acid	27	6-keto-Prostaglandin F_1α	1.97 ± 0.07	92	3.32	3.06	1500
(5Z,11α,13E) -11-Hydroxy-9,15-dioxoprosta-5,13-dien-1-oic acid	28	15-keto-Prostaglandin E₂	1.97 ± 0.12	93	2.60	2.15	240
(5Z,9α,11α,13E,15S) -6,9-Epoxy-11,15-dihydroxyprosta-5,13-dien-1-oic acid	29	Prostaglandin I₂	2.03 ± 0.12	110	N.D.	N.D.	N.D.
(9α,11α,13E,15S) -9,11,15-Trihydroxyprost-13-en-1-oic acid	30	Prostaglandin F_1α	2.09 ± 0.08	120	2.89	2.55	530
(11β,13E,15S) -11,15-Dihydroxy-9-oxoprost-13-en-1-oic acid	31	11β-Prostaglandin E₁	2.15 ± 0.04	140	2.70	2.50	400
(5Z,11α,13E,15S,19R) -11,15,19-Trihydroxy-9-oxoprosta-5,13-dien-1-oic acid	32 ^1-a	19(R) -Hydroxy prostaglandin E₂	2.19 ± 0.33	150	2.77	2.74	570
(5Z,11α) -11-Hydroxy-9,15-dioxo-prost-5-en-1-oic acid	33	13,14-Dihydro-15-keto-prostaglandin E₂	2.39 ± 0.05	250	2.98	2.67	670
(5Z,11α,13E,15S) -11,15-Dihydroxy-9-oxoprosta-5,13-dien-1-oic acid methyl ester	34	Prostaglandin E₂ methyl ester	2.40 ± 0.14	250	2.21	2.23	170
(13E,15S) -15-Hydroxy-9-oxoprost-13-en-1-oic acid	35	11-Deoxy-prostaglandin E₁	2.43 ± 0.05	270	2.85	2.33	390
(11α,13E) -11,16-Dihydroxy-16-methyl-9-oxoprost-13-en-1-oic acid	36	Misoprostol free acid	2.52 ± 0.08	330	3.42	2.92	1500
(5Z,9α,11α,15S) -9,11,15-Trihydroxyprost-5-en-1-oic acid	37	13,14-Dihydro-prostaglandin F_2α	2.53 ± 0.10	340	3.22	2.79	1000
(11α,13E,15R) -11,15-Dihydroxy-9-oxoprost-13-en-1-oic acid	38	15(R) -Prostaglandin E₁	2.66 ± 0.06	460	3.32	3.15	1700
(5Z,8β,9α,11α,13E,15S) -9,11,15-Trihydroxyprosta-5,13-dien-1-oic acid	39	8-iso-Prostaglandin F_2α	2.70 ± 0.04	510	2.94	2.97	900
(5Z,11α,13E,15R) -11,15-Dihydroxy-15-methyl-9-oxoprosta-5,13-dien-1-oic acid	40	15(R) -15-Methyl-prostaglandin E₂	2.73 ± 0.11	540	3.04	2.75	790
(5Z,13E,15S) -15-Hydroxy-9-oxoprosta-5,10,13-trien-1-oic acid	41	Prostaglandin A₂	2.87 ± 0.19	750	2.99	2.93	920
(5Z,11α,13E,15R) -11,15-Dihydroxy-9-oxoprosta-5,13-dien-1-oic acid	42	15(R) -Prostaglandin E₂	2.94 ± 0.10	870	3.50	3.29	2500
[1R-[1α,4α,5β(Z),6α(1E,3S^*)]] -7-[6-(3-Hydroxy-1-octenyl)-2-oxabicyclo[2.2.1]hept-5-yl]-5-heptenoic acid	43	U46619	3.00 ± 0.06	990	3.25	3.27	1800
(5Z,11α,13E,15S) -11,15-Dihydroxy- N -(2-hydroxyethyl)-9-oxoprosta-5,13-dien-1-amide	44	Prostaglandin E₂ ethanolamide	3.00 ± 0.05	1000	3.06	2.92	970
(5Z,9α,13E,15S) -9,15-dihydroxy-11-oxoprosta-5,13-dien-1-oic acid	45	Prostaglandin D₂	3.04 ± 0.05	1100	2.82	2.75	610
(13E,15S) -15-Hydroxy-9,11-dioxoprost-13-en-1-oic acid	46	Prostaglandin K₁	3.09 ± 0.11	1200	>3.50	3.40	2800
(11α,13E,15S) -11,15-Dihydroxy-9-oxoprost-13-en-1-oic acid methyl ester	47	Prostaglandin E₁ methyl ester	3.13 ± 0.20	1300	3.11	3.04	1200
(5Z,9α,11β,13E,15S) -9,11,15-Trihydroxyprosta-5,13-dien-1-oic acid	48	9α-11β-Prostaglandin F₂	3.16 ± 0.13	1500	3.36	3.27	2100
[1α(Z),2β(1E,3R^*), 3α,5α]-(±)-7-[3,5-Dihydroxy-2-[3-hydroxy-4-[3-(trifluoromethyl)phenoxy]-1-butenyl]cyclopentyl]-5-heptenoic acid	49	Fluprostenol	3.30 ± 0.02	2000	3.79	3.74	5800
(5Z,9α,11α,13E,15S) -9,11,15-Trihydroxyprosta-5,13-dien-1-oic acid methyl ester	50	Prostaglandin F_2α methyl ester	>3.4^±N.A.	>2400	3.57	3.18	2400
[1R-[1α(Z),2β(R^*), 3α,5α]]-7-[3,5-Dihydroxy-2-(3-hydroxy-5-phenylpentyl)cyclopentyl]-5-heptenoic acid 1-methylethylester	51	Latanoprost isopropyl ester	>3.4 ± N.A.	>2600	2.52	2.83	470
(5Z,9α,11α,13E,15R) -9,11,15-Trihydroxyprosta-5,13-dien-1-oic acid	52	15(R) -Prostaglandin F_2α	>3.6 ± N.A.	>4000	>3.6	>3.8	>5000
(5Z,13E,15S) -15-Hydroxy-9,11-dioxoprosta-5,13-dien-1-oic acid	53	Prostaglandin K₂	>3.9 ± N.A.	>8000	>3.6	>3.8	>5000
(5Z,9α,13E,15S) -9,11,15-Trihydroxythromboxa-5,13-dien-1-oic acid	54	Thromboxane B₂	>4.0 ± N.A.	>10000	>3.6	>3.8	>5000
(11α,13E) -11,16-Dihydroxy-16-methyl-9-oxoprost-13-en-1-oic acid methyl ester	55	Misoprostol methyl ester	≫4.0 ± N.A.	≫10000	3.64	3.70	4700

The relative aequorin response data (Log₁₀ relative aequorin) is presented as the average of triplicate experiments, ± 1 S.D., whereas for Log₁₀ relative binding data (Log₁₀ relative binding), both data points from duplicate experiments are presented. For ease of interpretation, the relative aequorin response is also presented as a simple nonlogarithmic ratio. Overall, in the activity assay, the EC₅₀ value for PGE₂ = 2.90 nM (n = 69), and in the binding assay, the K_i value for PGE₂ = 9.9 nM (n = 18). Compound numbers are assigned based on rank order of potency in the aequorin assay. In the aequorin assay, all differences in activity of ≥0.5 log units (≥ 3-fold difference in EC₅₀) are statistically significant (2-tailed t test, α = 0.05 for each individual comparison) with the exception of those involving 19(R) -hydroxy PGE₂ (32). Statistical analysis was not possible for compounds 50 to 55because the concentration-response curves did not reach a plateau at the maximum concentrations tested.

N.D., not determined; N.A., not applicable.
↵1-a Interexperimental variation was comparatively greater for this compound, the activity of which is significantly lower than that of M&B 28767 (20) and all more active compounds (1–19), and significantly higher than PGA₂(41) and all less active compounds (42–49).