|
The compound was tested for inhibition of dog platelet aggregation induced by ADP
|
Canis lupus familiaris
|
0.0038
ug.mL-1
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Syntheses of new 3-oxa-methano-PGI1 derivatives and their biological properties
Year : 1993
Volume : 3
Issue : 12
First Page : 2821
Last Page : 2826
Authors : Kawakami H, Muraoka M, Sugie A, Ono K, Kojima A
|
The compound was tested for inhibition of guinea pig platelet aggregation induced by ADP
|
Cavia porcellus
|
0.0025
ug.mL-1
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Syntheses of new 3-oxa-methano-PGI1 derivatives and their biological properties
Year : 1993
Volume : 3
Issue : 12
First Page : 2821
Last Page : 2826
Authors : Kawakami H, Muraoka M, Sugie A, Ono K, Kojima A
|
Inhibitory activity against ADP-induced platelet aggregation using human platelet rich plasma at a concentration of 4 uM by functional assay
|
Homo sapiens
|
70.0
nM
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Molecular design of novel PGI2 agonists without PG skeleton. II
Year : 1995
Volume : 5
Issue : 10
First Page : 1071
Last Page : 1076
Authors : Hamanaka N, Takahashi K, Nagao Y, Torisu K, Takada H, Tokumoto H, Kondo K
|
The compound was tested for inhibition of human platelet aggregation induced by ADP
|
Homo sapiens
|
0.0136
ug.mL-1
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Syntheses of new 3-oxa-methano-PGI1 derivatives and their biological properties
Year : 1993
Volume : 3
Issue : 12
First Page : 2821
Last Page : 2826
Authors : Kawakami H, Muraoka M, Sugie A, Ono K, Kojima A
|
Inhibitory concentration required to inhibit ADP-induced platelet aggregation in human platelet rich plasma
|
Homo sapiens
|
0.01
ug.mL-1
|
|
Journal : J. Med. Chem.
Title : Synthesis of acylguanidine analogues: inhibitors of ADP-induced platelet aggregation.
Year : 1989
Volume : 32
Issue : 1
First Page : 228
Last Page : 236
Authors : Thomas EW, Nishizawa EE, Zimmermann DC, Williams DJ.
Abstract : Routine screening of compounds for inhibition of ADP-induced platelet aggregation in vitro revealed that 1,1'-hexamethylenebis[3-cyclohexyl-3-[(cyclohexylimino) (4-morpholinyl) methyl]urea] (1) was active and represented the first example of a bis(acylguanidine) with possible antithrombotic activity. In order to develop a structure-activity relationship for this class of compounds, we synthesized a number of new bis(acylguanidines). These were tested in vitro, and several analogues were also active. Ex vivo testing revealed that compounds 22, 41, 58, and 70-73 were orally active in rats or guinea pigs.
|
Inhibitory activity against ADP-induced platelet aggregation at concentration 10 ng/mL
|
Homo sapiens
|
56.0
%
|
|
Inhibitory activity against ADP-induced platelet aggregation at concentration 10 ng/mL
|
Homo sapiens
|
28.0
%
|
|
Inhibitory activity against ADP-induced platelet aggregation at concentration 10 ng/mL
|
Homo sapiens
|
37.0
%
|
|
Journal : J. Med. Chem.
Title : Synthesis of acylguanidine analogues: inhibitors of ADP-induced platelet aggregation.
Year : 1989
Volume : 32
Issue : 1
First Page : 228
Last Page : 236
Authors : Thomas EW, Nishizawa EE, Zimmermann DC, Williams DJ.
Abstract : Routine screening of compounds for inhibition of ADP-induced platelet aggregation in vitro revealed that 1,1'-hexamethylenebis[3-cyclohexyl-3-[(cyclohexylimino) (4-morpholinyl) methyl]urea] (1) was active and represented the first example of a bis(acylguanidine) with possible antithrombotic activity. In order to develop a structure-activity relationship for this class of compounds, we synthesized a number of new bis(acylguanidines). These were tested in vitro, and several analogues were also active. Ex vivo testing revealed that compounds 22, 41, 58, and 70-73 were orally active in rats or guinea pigs.
|
Inhibitory activity against ADP-induced platelet aggregation at concentration 3.2 ng/mL
|
Homo sapiens
|
26.0
%
|
|
Inhibitory activity against ADP-induced platelet aggregation at concentration 3.2 ng/mL
|
Homo sapiens
|
1.0
%
|
|
Inhibitory activity against ADP-induced platelet aggregation at concentration 3.2 ng/mL
|
Homo sapiens
|
14.0
%
|
|
Journal : J. Med. Chem.
Title : Synthesis of acylguanidine analogues: inhibitors of ADP-induced platelet aggregation.
Year : 1989
Volume : 32
Issue : 1
First Page : 228
Last Page : 236
Authors : Thomas EW, Nishizawa EE, Zimmermann DC, Williams DJ.
Abstract : Routine screening of compounds for inhibition of ADP-induced platelet aggregation in vitro revealed that 1,1'-hexamethylenebis[3-cyclohexyl-3-[(cyclohexylimino) (4-morpholinyl) methyl]urea] (1) was active and represented the first example of a bis(acylguanidine) with possible antithrombotic activity. In order to develop a structure-activity relationship for this class of compounds, we synthesized a number of new bis(acylguanidines). These were tested in vitro, and several analogues were also active. Ex vivo testing revealed that compounds 22, 41, 58, and 70-73 were orally active in rats or guinea pigs.
|
Inhibitory activity against ADP-induced platelet aggregation at concentration 32 ng/mL
|
Homo sapiens
|
94.0
%
|
|
Inhibitory activity against ADP-induced platelet aggregation at concentration 32 ng/mL
|
Homo sapiens
|
90.0
%
|
|
Inhibitory activity against ADP-induced platelet aggregation at concentration 32 ng/mL
|
Homo sapiens
|
72.0
%
|
|
Journal : J. Med. Chem.
Title : Synthesis of acylguanidine analogues: inhibitors of ADP-induced platelet aggregation.
Year : 1989
Volume : 32
Issue : 1
First Page : 228
Last Page : 236
Authors : Thomas EW, Nishizawa EE, Zimmermann DC, Williams DJ.
Abstract : Routine screening of compounds for inhibition of ADP-induced platelet aggregation in vitro revealed that 1,1'-hexamethylenebis[3-cyclohexyl-3-[(cyclohexylimino) (4-morpholinyl) methyl]urea] (1) was active and represented the first example of a bis(acylguanidine) with possible antithrombotic activity. In order to develop a structure-activity relationship for this class of compounds, we synthesized a number of new bis(acylguanidines). These were tested in vitro, and several analogues were also active. Ex vivo testing revealed that compounds 22, 41, 58, and 70-73 were orally active in rats or guinea pigs.
|
Binding affinity towards mouse Prostanoid EP1 receptor in CHO cells.
|
None
|
100.0
nM
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Design and synthesis of a highly selective EP2-receptor agonist.
Year : 2001
Volume : 11
Issue : 15
First Page : 2025
Last Page : 2028
Authors : Tani K, Naganawa A, Ishida A, Egashira H, Sagawa K, Harada H, Ogawa M, Maruyama T, Ohuchida S, Nakai H, Kondo K, Toda M.
Abstract : EP2-receptor selective agonist 3 was identified by the structural hybridization of butaprost 1a and PGE(2) 2a. Based on this information, a chemically more stabilized 4 was discovered as another highly selective EP2-receptor agonist, iv administration of which to anesthetized rats suppressed uterine motility, while PGE(2) 2a stimulated uterine motility.
|
Evaluated for its competitive binding affinity towards mouse Prostanoid EP1 receptor in CHO cells expressing prostanoid receptor
|
None
|
22.0
nM
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Design and synthesis of a highly selective EP4-receptor agonist. Part 1: 3,7-dithiaPG derivatives with high selectivity.
Year : 2001
Volume : 11
Issue : 15
First Page : 2029
Last Page : 2031
Authors : Maruyama T, Asada M, Shiraishi T, Ishida A, Egashira H, Yoshida H, Maruyama T, Ohuchida S, Nakai H, Kondo K, Toda M.
Abstract : A series of 3,7-dithiaPGE(1) analogues 3, 4, 11, 16 and 19 were identified as highly selective EP4-receptor agonists starting from the chemical modification of 7-thiaPGE(1) analogue 1. EP4-receptor selectivity and agonist activity were maximized in 3 and 4.
|
Affinity for mouse Prostanoid EP1 receptor expressed in CHO cells
|
Mus musculus
|
22.0
nM
|
|
Affinity for mouse Prostanoid EP1 receptor expressed in CHO cells
|
Mus musculus
|
6.0
nM
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Design and synthesis of a highly selective EP4-receptor agonist. Part 2: 5-thia and 9beta-haloPG derivatives with improved stability.
Year : 2001
Volume : 11
Issue : 15
First Page : 2033
Last Page : 2035
Authors : Maruyama T, Asada M, Shiraishi T, Sakata K, Seki A, Yoshida H, Shinagawa Y, Maruyama T, Ohuchida S, Nakai H, Kondo K, Toda M.
Abstract : Further chemical modification to identify more chemically stabilized EP4-receptor selective agonists was continued. As a result, a further two EP4-receptor selective agonists 5-thiaPGE(1) 2a, 10 and 9beta-chloroPGF(2) analogue 11 were discovered.
|
Effective concentration which increases intracellular c-AMP production in mouse Prostanoid EP2 receptor
|
None
|
2.6
nM
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Design and synthesis of a highly selective EP2-receptor agonist.
Year : 2001
Volume : 11
Issue : 15
First Page : 2025
Last Page : 2028
Authors : Tani K, Naganawa A, Ishida A, Egashira H, Sagawa K, Harada H, Ogawa M, Maruyama T, Ohuchida S, Nakai H, Kondo K, Toda M.
Abstract : EP2-receptor selective agonist 3 was identified by the structural hybridization of butaprost 1a and PGE(2) 2a. Based on this information, a chemically more stabilized 4 was discovered as another highly selective EP2-receptor agonist, iv administration of which to anesthetized rats suppressed uterine motility, while PGE(2) 2a stimulated uterine motility.
|
Binding affinity towards mouse Prostanoid EP2 receptor expressed in CHO cells.
|
None
|
87.0
nM
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Design and synthesis of a highly selective EP2-receptor agonist.
Year : 2001
Volume : 11
Issue : 15
First Page : 2025
Last Page : 2028
Authors : Tani K, Naganawa A, Ishida A, Egashira H, Sagawa K, Harada H, Ogawa M, Maruyama T, Ohuchida S, Nakai H, Kondo K, Toda M.
Abstract : EP2-receptor selective agonist 3 was identified by the structural hybridization of butaprost 1a and PGE(2) 2a. Based on this information, a chemically more stabilized 4 was discovered as another highly selective EP2-receptor agonist, iv administration of which to anesthetized rats suppressed uterine motility, while PGE(2) 2a stimulated uterine motility.
|
Evaluated for its competitive binding affinity towards mouse Prostanoid EP2 receptor in CHO cells expressing prostanoid receptor
|
None
|
41.0
nM
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Design and synthesis of a highly selective EP4-receptor agonist. Part 1: 3,7-dithiaPG derivatives with high selectivity.
Year : 2001
Volume : 11
Issue : 15
First Page : 2029
Last Page : 2031
Authors : Maruyama T, Asada M, Shiraishi T, Ishida A, Egashira H, Yoshida H, Maruyama T, Ohuchida S, Nakai H, Kondo K, Toda M.
Abstract : A series of 3,7-dithiaPGE(1) analogues 3, 4, 11, 16 and 19 were identified as highly selective EP4-receptor agonists starting from the chemical modification of 7-thiaPGE(1) analogue 1. EP4-receptor selectivity and agonist activity were maximized in 3 and 4.
|
Affinity for mouse Prostanoid EP2 receptor expressed in CHO cells
|
Mus musculus
|
41.0
nM
|
|
Affinity for mouse Prostanoid EP2 receptor expressed in CHO cells
|
Mus musculus
|
22.0
nM
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Design and synthesis of a highly selective EP4-receptor agonist. Part 2: 5-thia and 9beta-haloPG derivatives with improved stability.
Year : 2001
Volume : 11
Issue : 15
First Page : 2033
Last Page : 2035
Authors : Maruyama T, Asada M, Shiraishi T, Sakata K, Seki A, Yoshida H, Shinagawa Y, Maruyama T, Ohuchida S, Nakai H, Kondo K, Toda M.
Abstract : Further chemical modification to identify more chemically stabilized EP4-receptor selective agonists was continued. As a result, a further two EP4-receptor selective agonists 5-thiaPGE(1) 2a, 10 and 9beta-chloroPGF(2) analogue 11 were discovered.
|
Binding affinity towards mouse Prostanoid EP3 receptor in CHO cells.
|
None
|
5.0
nM
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Design and synthesis of a highly selective EP2-receptor agonist.
Year : 2001
Volume : 11
Issue : 15
First Page : 2025
Last Page : 2028
Authors : Tani K, Naganawa A, Ishida A, Egashira H, Sagawa K, Harada H, Ogawa M, Maruyama T, Ohuchida S, Nakai H, Kondo K, Toda M.
Abstract : EP2-receptor selective agonist 3 was identified by the structural hybridization of butaprost 1a and PGE(2) 2a. Based on this information, a chemically more stabilized 4 was discovered as another highly selective EP2-receptor agonist, iv administration of which to anesthetized rats suppressed uterine motility, while PGE(2) 2a stimulated uterine motility.
|
Evaluated for its competitive binding affinity towards mouse Prostanoid EP3 receptor in CHO cells expressing prostanoid receptor
|
None
|
5.0
nM
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Design and synthesis of a highly selective EP4-receptor agonist. Part 1: 3,7-dithiaPG derivatives with high selectivity.
Year : 2001
Volume : 11
Issue : 15
First Page : 2029
Last Page : 2031
Authors : Maruyama T, Asada M, Shiraishi T, Ishida A, Egashira H, Yoshida H, Maruyama T, Ohuchida S, Nakai H, Kondo K, Toda M.
Abstract : A series of 3,7-dithiaPGE(1) analogues 3, 4, 11, 16 and 19 were identified as highly selective EP4-receptor agonists starting from the chemical modification of 7-thiaPGE(1) analogue 1. EP4-receptor selectivity and agonist activity were maximized in 3 and 4.
|
Affinity for mouse Prostanoid EP3 receptor expressed in CHO cells
|
Mus musculus
|
5.0
nM
|
|
Affinity for mouse Prostanoid EP3 receptor expressed in CHO cells
|
Mus musculus
|
5.0
nM
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Design and synthesis of a highly selective EP4-receptor agonist. Part 2: 5-thia and 9beta-haloPG derivatives with improved stability.
Year : 2001
Volume : 11
Issue : 15
First Page : 2033
Last Page : 2035
Authors : Maruyama T, Asada M, Shiraishi T, Sakata K, Seki A, Yoshida H, Shinagawa Y, Maruyama T, Ohuchida S, Nakai H, Kondo K, Toda M.
Abstract : Further chemical modification to identify more chemically stabilized EP4-receptor selective agonists was continued. As a result, a further two EP4-receptor selective agonists 5-thiaPGE(1) 2a, 10 and 9beta-chloroPGF(2) analogue 11 were discovered.
|
Effective concentration which increases intracellular c-AMP production in mouse Prostanoid EP4 receptor
|
None
|
2.5
nM
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Design and synthesis of a highly selective EP4-receptor agonist. Part 1: 3,7-dithiaPG derivatives with high selectivity.
Year : 2001
Volume : 11
Issue : 15
First Page : 2029
Last Page : 2031
Authors : Maruyama T, Asada M, Shiraishi T, Ishida A, Egashira H, Yoshida H, Maruyama T, Ohuchida S, Nakai H, Kondo K, Toda M.
Abstract : A series of 3,7-dithiaPGE(1) analogues 3, 4, 11, 16 and 19 were identified as highly selective EP4-receptor agonists starting from the chemical modification of 7-thiaPGE(1) analogue 1. EP4-receptor selectivity and agonist activity were maximized in 3 and 4.
|
Effective concentration for increased intracellular c-AMP production by mouse Prostanoid EP4 receptor
|
Mus musculus
|
2.5
nM
|
|
Effective concentration for increased intracellular c-AMP production by mouse Prostanoid EP4 receptor
|
Mus musculus
|
3.6
nM
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Design and synthesis of a highly selective EP4-receptor agonist. Part 2: 5-thia and 9beta-haloPG derivatives with improved stability.
Year : 2001
Volume : 11
Issue : 15
First Page : 2033
Last Page : 2035
Authors : Maruyama T, Asada M, Shiraishi T, Sakata K, Seki A, Yoshida H, Shinagawa Y, Maruyama T, Ohuchida S, Nakai H, Kondo K, Toda M.
Abstract : Further chemical modification to identify more chemically stabilized EP4-receptor selective agonists was continued. As a result, a further two EP4-receptor selective agonists 5-thiaPGE(1) 2a, 10 and 9beta-chloroPGF(2) analogue 11 were discovered.
|
Binding affinity towards mouse Prostanoid EP4 receptor in CHO cells.
|
None
|
3.3
nM
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Design and synthesis of a highly selective EP2-receptor agonist.
Year : 2001
Volume : 11
Issue : 15
First Page : 2025
Last Page : 2028
Authors : Tani K, Naganawa A, Ishida A, Egashira H, Sagawa K, Harada H, Ogawa M, Maruyama T, Ohuchida S, Nakai H, Kondo K, Toda M.
Abstract : EP2-receptor selective agonist 3 was identified by the structural hybridization of butaprost 1a and PGE(2) 2a. Based on this information, a chemically more stabilized 4 was discovered as another highly selective EP2-receptor agonist, iv administration of which to anesthetized rats suppressed uterine motility, while PGE(2) 2a stimulated uterine motility.
|
Evaluated for its competitive binding affinity towards mouse Prostanoid EP4 receptor in CHO cells expressing prostanoid receptor
|
None
|
3.3
nM
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Design and synthesis of a highly selective EP4-receptor agonist. Part 1: 3,7-dithiaPG derivatives with high selectivity.
Year : 2001
Volume : 11
Issue : 15
First Page : 2029
Last Page : 2031
Authors : Maruyama T, Asada M, Shiraishi T, Ishida A, Egashira H, Yoshida H, Maruyama T, Ohuchida S, Nakai H, Kondo K, Toda M.
Abstract : A series of 3,7-dithiaPGE(1) analogues 3, 4, 11, 16 and 19 were identified as highly selective EP4-receptor agonists starting from the chemical modification of 7-thiaPGE(1) analogue 1. EP4-receptor selectivity and agonist activity were maximized in 3 and 4.
|
Affinity for mouse Prostanoid EP4 receptor expressed in CHO cells
|
Mus musculus
|
3.3
nM
|
|
Affinity for mouse Prostanoid EP4 receptor expressed in CHO cells
|
Mus musculus
|
3.1
nM
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Design and synthesis of a highly selective EP4-receptor agonist. Part 2: 5-thia and 9beta-haloPG derivatives with improved stability.
Year : 2001
Volume : 11
Issue : 15
First Page : 2033
Last Page : 2035
Authors : Maruyama T, Asada M, Shiraishi T, Sakata K, Seki A, Yoshida H, Shinagawa Y, Maruyama T, Ohuchida S, Nakai H, Kondo K, Toda M.
Abstract : Further chemical modification to identify more chemically stabilized EP4-receptor selective agonists was continued. As a result, a further two EP4-receptor selective agonists 5-thiaPGE(1) 2a, 10 and 9beta-chloroPGF(2) analogue 11 were discovered.
|
Effective concentration which increases intracellular c-AMP production in human Prostanoid IP receptor
|
None
|
1.8
nM
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Design and synthesis of a highly selective EP2-receptor agonist.
Year : 2001
Volume : 11
Issue : 15
First Page : 2025
Last Page : 2028
Authors : Tani K, Naganawa A, Ishida A, Egashira H, Sagawa K, Harada H, Ogawa M, Maruyama T, Ohuchida S, Nakai H, Kondo K, Toda M.
Abstract : EP2-receptor selective agonist 3 was identified by the structural hybridization of butaprost 1a and PGE(2) 2a. Based on this information, a chemically more stabilized 4 was discovered as another highly selective EP2-receptor agonist, iv administration of which to anesthetized rats suppressed uterine motility, while PGE(2) 2a stimulated uterine motility.
|
Binding affinity towards human Prostanoid IP receptor in CHO cells.
|
None
|
150.0
nM
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Design and synthesis of a highly selective EP2-receptor agonist.
Year : 2001
Volume : 11
Issue : 15
First Page : 2025
Last Page : 2028
Authors : Tani K, Naganawa A, Ishida A, Egashira H, Sagawa K, Harada H, Ogawa M, Maruyama T, Ohuchida S, Nakai H, Kondo K, Toda M.
Abstract : EP2-receptor selective agonist 3 was identified by the structural hybridization of butaprost 1a and PGE(2) 2a. Based on this information, a chemically more stabilized 4 was discovered as another highly selective EP2-receptor agonist, iv administration of which to anesthetized rats suppressed uterine motility, while PGE(2) 2a stimulated uterine motility.
|
Evaluated for its competitive binding affinity towards human Prostanoid IP receptor in CHO cells
|
None
|
150.0
nM
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Design and synthesis of a highly selective EP4-receptor agonist. Part 1: 3,7-dithiaPG derivatives with high selectivity.
Year : 2001
Volume : 11
Issue : 15
First Page : 2029
Last Page : 2031
Authors : Maruyama T, Asada M, Shiraishi T, Ishida A, Egashira H, Yoshida H, Maruyama T, Ohuchida S, Nakai H, Kondo K, Toda M.
Abstract : A series of 3,7-dithiaPGE(1) analogues 3, 4, 11, 16 and 19 were identified as highly selective EP4-receptor agonists starting from the chemical modification of 7-thiaPGE(1) analogue 1. EP4-receptor selectivity and agonist activity were maximized in 3 and 4.
|
Affinity for human Prostanoid IP receptor expressed in CHO cells
|
Homo sapiens
|
150.0
nM
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Design and synthesis of a highly selective EP4-receptor agonist. Part 2: 5-thia and 9beta-haloPG derivatives with improved stability.
Year : 2001
Volume : 11
Issue : 15
First Page : 2033
Last Page : 2035
Authors : Maruyama T, Asada M, Shiraishi T, Sakata K, Seki A, Yoshida H, Shinagawa Y, Maruyama T, Ohuchida S, Nakai H, Kondo K, Toda M.
Abstract : Further chemical modification to identify more chemically stabilized EP4-receptor selective agonists was continued. As a result, a further two EP4-receptor selective agonists 5-thiaPGE(1) 2a, 10 and 9beta-chloroPGF(2) analogue 11 were discovered.
|
The compound was tested for inhibition of rabbit platelet aggregation induced by ADP
|
Oryctolagus cuniculus
|
0.0207
ug.mL-1
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Syntheses of new 3-oxa-methano-PGI1 derivatives and their biological properties
Year : 1993
Volume : 3
Issue : 12
First Page : 2821
Last Page : 2826
Authors : Kawakami H, Muraoka M, Sugie A, Ono K, Kojima A
|
The compound was tested for inhibition of rabbit platelet aggregation induced by arachidonic acid
|
Oryctolagus cuniculus
|
0.0359
ug.mL-1
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Syntheses of new 3-oxa-methano-PGI1 derivatives and their biological properties
Year : 1993
Volume : 3
Issue : 12
First Page : 2821
Last Page : 2826
Authors : Kawakami H, Muraoka M, Sugie A, Ono K, Kojima A
|
The compound was tested for inhibition of rabbit platelet aggregation induced by collagen
|
Oryctolagus cuniculus
|
0.0132
ug.mL-1
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Syntheses of new 3-oxa-methano-PGI1 derivatives and their biological properties
Year : 1993
Volume : 3
Issue : 12
First Page : 2821
Last Page : 2826
Authors : Kawakami H, Muraoka M, Sugie A, Ono K, Kojima A
|
The compound was tested for inhibition of rat platelet aggregation induced by ADP
|
Rattus norvegicus
|
0.0344
ug.mL-1
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Syntheses of new 3-oxa-methano-PGI1 derivatives and their biological properties
Year : 1993
Volume : 3
Issue : 12
First Page : 2821
Last Page : 2826
Authors : Kawakami H, Muraoka M, Sugie A, Ono K, Kojima A
|
PUBCHEM_BIOASSAY: Luminescence Cell-Based Dose Confirmation HTS to Identify Inhibitors of Platelet Dense Granule Release. (Class of assay: confirmatory) [Related pubchem assays: 1663 (Primary HTS), 1678 (Summary of Project)]
|
None
|
88.0
nM
|
|
Title : PubChem BioAssay data set
|
TP_TRANSPORTER: inhibition of PGD2 uptake in Xenopus laevis oocytes
|
Xenopus laevis
|
35.8
nM
|
|
Journal : Biochem. Biophys. Res. Commun.
Title : Molecular identification of a rat novel organic anion transporter moat1, which transports prostaglandin D(2), leukotriene C(4), and taurocholate.
Year : 2000
Volume : 275
Issue : 1
First Page : 831
Last Page : 838
Authors : Nishio T, Adachi H, Nakagomi R, Tokui T, Sato E, Tanemoto M, Fujiwara K, Okabe M, Onogawa T, Suzuki T, Nakai D, Shiiba K, Suzuki M, Ohtani H, Kondo Y, Unno M, Ito S, Iinuma K, Nunoki K, Matsuno S, Abe T.
Abstract : We have isolated a rat novel multispecific organic anion transporter, moat1. The isolated clones were originated by alternative splicing of the moat1 mRNA. The nucleotide sequences predict a protein of 682 amino acids with moderate sequence similarity to LST-1, the oatp family, and the prostaglandin transporter. Northern blot analysis of rat moat1 identified a predominant transcript of 4.4 kilonucleotides in all tissues. Northern blot and in situ hybridization analyses of rat brain further indicated that moat1 mRNA is widely distributed in neuronal cells of the central nervous system, especially in the hippocampus and cerebellum. moat1 transports prostaglandin D(2) (K(m); 35.5 nM), leukotriene C(4) (K(m); 3.2 microM) and taurocholate (K(m); 17.6 microM) in a sodium-independent manner. moat1 also transports prostaglandin E(1), E(2), thromboxane B(2), and iloprost but not dehydroepiandrosterone sulfate and digoxin, of which the substrate specificity is similar, but definitively different from those of any other organic anion transporters.
|
Inhibition of electric eel AChE at 2 mg/ml by Ellman's method
|
Electrophorus electricus
|
16.57
%
|
|
Journal : Bioorg. Med. Chem.
Title : Exploration of natural compounds as sources of new bifunctional scaffolds targeting cholinesterases and beta amyloid aggregation: the case of chelerythrine.
Year : 2012
Volume : 20
Issue : 22
First Page : 6669
Last Page : 6679
Authors : Brunhofer G, Fallarero A, Karlsson D, Batista-Gonzalez A, Shinde P, Gopi Mohan C, Vuorela P.
Abstract : The presented project started by screening a library consisting of natural and natural based compounds for their acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activity. Active compounds were chemically clustered into groups and further tested on the human cholinesterases isoforms. The aim of the presented study was to identify compounds that could be used as leads to target two key mechanisms associated with the AD's pathogenesis simultaneously: cholinergic depletion and beta amyloid (Aβ) aggregation. Berberin, palmatine and chelerythrine, chemically clustered in the so-called isoquinoline group, showed promising cholinesterase inhibitory activity and were therefore further investigated. Moreover, the compounds demonstrated moderate to good inhibition of Aβ aggregation as well as the ability to disaggregate already preformed Aβ aggregates in an experimental set-up using HFIP as promotor of Aβ aggregates. Analysis of the kinetic mechanism of the AChE inhibition revealed chelerythrine as a mixed inhibitor. Using molecular docking studies, it was further proven that chelerythrine binds on both the catalytic site and the peripheral anionic site (PAS) of the AChE. In view of this, we went on to investigate its effect on inhibiting Aβ aggregation stimulated by AChE. Chelerythrine showed inhibition of fibril formation in the same range as propidium iodide. This approach enabled for the first time to identify a cholinesterase inhibitor of natural origin-chelerythrine-acting on AChE and BChE with a dual ability to inhibit Aβ aggregation as well as to disaggregate preformed Aβ aggregates. This compound could be an excellent starting point paving the way to develop more successful anti-AD drugs.
|
Inhibition of horse BChE at 2 mg/ml by Ellman's method
|
Equus caballus
|
-1.69
%
|
|
Journal : Bioorg. Med. Chem.
Title : Exploration of natural compounds as sources of new bifunctional scaffolds targeting cholinesterases and beta amyloid aggregation: the case of chelerythrine.
Year : 2012
Volume : 20
Issue : 22
First Page : 6669
Last Page : 6679
Authors : Brunhofer G, Fallarero A, Karlsson D, Batista-Gonzalez A, Shinde P, Gopi Mohan C, Vuorela P.
Abstract : The presented project started by screening a library consisting of natural and natural based compounds for their acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activity. Active compounds were chemically clustered into groups and further tested on the human cholinesterases isoforms. The aim of the presented study was to identify compounds that could be used as leads to target two key mechanisms associated with the AD's pathogenesis simultaneously: cholinergic depletion and beta amyloid (Aβ) aggregation. Berberin, palmatine and chelerythrine, chemically clustered in the so-called isoquinoline group, showed promising cholinesterase inhibitory activity and were therefore further investigated. Moreover, the compounds demonstrated moderate to good inhibition of Aβ aggregation as well as the ability to disaggregate already preformed Aβ aggregates in an experimental set-up using HFIP as promotor of Aβ aggregates. Analysis of the kinetic mechanism of the AChE inhibition revealed chelerythrine as a mixed inhibitor. Using molecular docking studies, it was further proven that chelerythrine binds on both the catalytic site and the peripheral anionic site (PAS) of the AChE. In view of this, we went on to investigate its effect on inhibiting Aβ aggregation stimulated by AChE. Chelerythrine showed inhibition of fibril formation in the same range as propidium iodide. This approach enabled for the first time to identify a cholinesterase inhibitor of natural origin-chelerythrine-acting on AChE and BChE with a dual ability to inhibit Aβ aggregation as well as to disaggregate preformed Aβ aggregates. This compound could be an excellent starting point paving the way to develop more successful anti-AD drugs.
|
Inhibition of antigen-induced lymphocyte (unknown origin) transformation at 10 ug/mL relative to control
|
Not specified
|
82.0
%
|
|
Journal : J. Med. Chem.
Title : 11,12-Secoprostaglandins. 3. 8-Alkylthio(sulfinyl and sulfonyl)-12-hydroxyalkanoic acids and related compounds.
Year : 1977
Volume : 20
Issue : 4
First Page : 540
Last Page : 547
Authors : Smith RL, Bicking JB, Gould NP, Lee T, Robb CM, Kuehl FA, Mandel LR, Cragoe EJ.
Abstract : A series of 8-alkylthio(sulfinyl and sulfonyl)-12-hydroxyalkanoic acids which embody structural features of 11,12-secoprostaglandins was synthesized and evaluated for their ability to mimic the E series prostaglandins in stimulating cAMP formation in the mouse ovary and in binding to the rat lipocyte prostaglandin receptor. A key member of the series, 8-methylsulfonyl-12-hydroxyheptadecanoic acid, markedly stimulated cAMP formation at reasonable pharmacological concentrations, shows significant affinity for a prostaglandin receptor, and effectively inhibits antigen-induced lymphocyte transformation. In contrast, this compound is not a substrate for 15-hydroxyprostaglandin dehydrogenase, the major prostaglandin-metabolizing enzyme.
|
Antibacterial activity against Staphylococcus aureus MRSA ATCC 43300 (CO-ADD:GP_020); MIC in CAMBH media, using NBS plates, by OD(600)
|
Staphylococcus aureus subsp. aureus
|
3.1
%
|
|
|
Antibacterial activity against Escherichia coli ATCC 25922 (CO-ADD:GN_001); MIC in CAMBH media using NBS plates, by OD(600)
|
Escherichia coli
|
6.55
%
|
|
|
Antibacterial activity against Klebsiella pneumoniae MDR ATCC 70063 (CO-ADD:GN_003); MIC in CAMBH media using NBS plates, by OD(600)
|
Klebsiella pneumoniae
|
7.2
%
|
|
|
Antibacterial activity against Pseudomonas aeruginosa ATCC 27853 (CO-ADD:GN_042); MIC in CAMBH media using NBS plates, by OD(600)
|
Pseudomonas aeruginosa
|
6.38
%
|
|
|
Antibacterial activity against Acinetobacter baumannii ATCC 19606 (CO-ADD:GN_034); MIC in CAMBH media using NBS plates, by OD600
|
Acinetobacter baumannii
|
14.8
%
|
|
|
Antifungal activity against Candida albicans ATCC 90028 (CO-ADD:FG_001); MIC in YNB media using NBS plates, by OD630
|
Candida albicans
|
3.09
%
|
|
|
Antifungal activity against Cryptococcus neoformans H99 ATCC 208821 (CO-ADD:FG_002); MIC in YNB media using NBS plates, by Resazurin OD(600-570)
|
Cryptococcus neoformans
|
2.52
%
|
|
|
Antiviral activity determined as inhibition of SARS-CoV-2 induced cytotoxicity of Caco-2 cells at 10 uM after 48 hours by high content imaging
|
Homo sapiens
|
28.19
%
|
|
Title : Identification of inhibitors of SARS-CoV-2 in-vitro cellular toxicity in human (Caco-2) cells using a large scale drug repurposing collection
Year : 2020
Authors : Bernhard Ellinger, Denisa Bojkova, Andrea Zaliani, Jindrich Cinatl, Carsten Claussen, Sandra Westhaus, Jeanette Reinshagen, Maria Kuzikov, Markus Wolf, Gerd Geisslinger, Philip Gribbon, Sandra Ciesek
Abstract : To identify possible candidates for progression towards clinical studies against SARS-CoV-2, we screened a well-defined collection of 5632 compounds including 3488 compounds which have undergone clinical investigations (marketed drugs, phases 1 -3, and withdrawn) across 600 indications. Compounds were screened for their inhibition of viral induced cytotoxicity using the human epithelial colorectal adenocarcinoma cell line Caco-2 and a SARS-CoV-2 isolate. The primary screen of 5632 compounds gave 271 hits. A total of 64 compounds with IC50 <20 µM were identified, including 19 compounds with IC50 < 1 µM. Of this confirmed hit population, 90% have not yet been previously reported as active against SARS-CoV-2 in-vitro cell assays. Some 37 of the actives are launched drugs, 19 are in phases 1-3 and 10 pre-clinical. Several inhibitors were associated with modulation of host pathways including kinase signaling P53 activation, ubiquitin pathways and PDE activity modulation, with long chain acyl transferases were effective viral inhibitors.
|
SARS-CoV-2 3CL-Pro protease inhibition percentage at 20µM by FRET kind of response from peptide substrate
|
Severe acute respiratory syndrome coronavirus 2
|
14.92
%
|
|
SARS-CoV-2 3CL-Pro protease inhibition percentage at 20µM by FRET kind of response from peptide substrate
|
Severe acute respiratory syndrome coronavirus 2
|
8.93
%
|
|
SARS-CoV-2 3CL-Pro protease inhibition percentage at 20µM by FRET kind of response from peptide substrate
|
Severe acute respiratory syndrome coronavirus 2
|
0.4467
%
|
|
Title : Identification of inhibitors of SARS-Cov2 M-Pro enzymatic activity using a small molecule repurposing screen
Year : 2020
Authors : Maria Kuzikov, Elisa Costanzi, Jeanette Reinshagen, Francesca Esposito, Laura Vangeel, Markus Wolf, Bernhard Ellinger, Carsten Claussen, Gerd Geisslinger, Angela Corona, Daniela Iaconis, Carmine Talarico, Candida Manelfi, Rolando Cannalire, Giulia Rossetti, Jonas Gossen, Simone Albani, Francesco Musiani, Katja Herzog, Yang Ye, Barbara Giabbai, Nicola Demitri, Dirk Jochmans, Steven De Jonghe, Jasper Rymenants, Vincenzo Summa, Enzo Tramontano, Andrea R. Beccari, Pieter Leyssen, Paola Storici, Johan Neyts, Philip Gribbon, and Andrea Zaliani
Abstract : Compound repurposing is an important strategy being pursued in the identification of effective treatment against the SARS-CoV-2 infection and COVID-19 disease. In this regard, SARS-CoV-2 main protease (M-Pro), also termed 3CL-Pro, is an attractive drug target as it plays a central role in viral replication by processing the viral polyprotein into 11 non-structural proteins. We report the results of a screening campaign involving ca 8.7 K compounds containing marketed drugs, clinical and preclinical candidates, and chemicals regarded as safe in humans. We confirmed previously reported inhibitors of 3CL-Pro, but we have also identified 68 compounds with IC50 lower than 1 uM and 127 compounds with IC50 lower than 5 uM. Profiling showed 67% of confirmed hits were selective (> 5 fold) against other Cys- and Ser- proteases (Chymotrypsin and Cathepsin-L) and MERS 3CL-Pro. Selected compounds were also analysed in their binding characteristics.
|
Antiviral activity determined as inhibition of SARS-CoV-2 induced cytotoxicity of VERO-6 cells at 10 uM after 48 hours exposure to 0.01 MOI SARS CoV-2 virus by high content imaging
|
Chlorocebus sabaeus
|
0.15
%
|
|
Antiviral activity determined as inhibition of SARS-CoV-2 induced cytotoxicity of VERO-6 cells at 10 uM after 48 hours exposure to 0.01 MOI SARS CoV-2 virus by high content imaging
|
Chlorocebus sabaeus
|
0.15
%
|
|
Antiviral activity determined as inhibition of SARS-CoV-2 induced cytotoxicity of VERO-6 cells at 10 uM after 48 hours exposure to 0.01 MOI SARS CoV-2 virus by high content imaging
|
Chlorocebus sabaeus
|
0.22
%
|
|
Antiviral activity determined as inhibition of SARS-CoV-2 induced cytotoxicity of VERO-6 cells at 10 uM after 48 hours exposure to 0.01 MOI SARS CoV-2 virus by high content imaging
|
Chlorocebus sabaeus
|
0.22
%
|
|
Antiviral activity determined as inhibition of SARS-CoV-2 induced cytotoxicity of VERO-6 cells at 10 uM after 48 hours exposure to 0.01 MOI SARS CoV-2 virus by high content imaging
|
Chlorocebus sabaeus
|
0.15
%
|
|
Antiviral activity determined as inhibition of SARS-CoV-2 induced cytotoxicity of VERO-6 cells at 10 uM after 48 hours exposure to 0.01 MOI SARS CoV-2 virus by high content imaging
|
Chlorocebus sabaeus
|
0.15
%
|
|
Title : Cytopathic SARS-Cov2 screening on VERO-E6 cells in a large repurposing effort
Year : 2020
Authors : Andrea Zaliani, Laura Vangeel, Jeanette Reinshagen, Daniela Iaconis, Maria Kuzikov, Oliver Keminer, Markus Wolf, Bernhard Ellinger, Francesca Esposito, Angela Corona, Enzo Tramontano, Candida Manelfi, Katja Herzog, Dirk Jochmans, Steven De Jonghe, Winston Chiu, Thibault Francken, Joost Schepers, Caroline Collard, Kayvan Abbasi, Carsten Claussen , Vincenzo Summa, Andrea R. Beccari, Johan Neyts, Philip Gribbon and Pieter Leyssen
Abstract : Worldwide, there are intensive efforts to identify repurposed drugs as potential therapies against SARS-CoV-2 infection and the associated COVID-19 disease. To date, the anti-inflammatory drug dexamethasone and (to a lesser extent) the RNA-polymerase inhibitor remdesivir have been shown to be effective in reducing mortality and patient time to recovery, respectively, in patients. Here, we report the results of a phenotypic screening campaign within an EU-funded project (H2020-EXSCALATE4COV) aimed at extending the repertoire of anti-COVID therapeutics through repurposing of available compounds and highlighting compounds with new mechanisms of action against viral infection. We screened 8702 molecules from different repurposing libraries, to reveal 110 compounds with an anti-cytopathic IC50 < 20 µM. From this group, 18 with a safety index greater than 2 are also marketed drugs, making them suitable for further study as potential therapies against COVID-19. Our result supports the idea that a systematic approach to repurposing is a valid strategy to accelerate the necessary drug discovery process.
