pig-1

Etomoxir是一种不可逆的肉毒碱棕榈酰转移酶1a (CPT-1a) 抑制剂 (IC50=5-20 nM) 。Etomoxir通过抑制 CPT-1a 来抑制脂肪酸氧化，抑制棕榈酸酯的氧化，对腺嘌呤核苷酸转位酶有抑制作用，可通过破坏CoA稳态来抑制巨噬细胞极化。

Litoxetine HCl 是一种选择性5-羟色胺（5-HT）再摄取抑制剂（SSRI）和混合5-羟色胺拮抗剂，可用于治疗尿失禁。Litoxetine HCl 在没有抗毒蕈碱特性的浓度下（10 nM-1 microM）引起大鼠离体食道肌肉粘膜的浓度依赖性松弛，使卡巴胆碱张力降低达37%,更高浓度的Litoxetine HCl（3微摩-300微摩）与明显的松弛有关，直至取消卡巴胆碱张力。以前在离体豚鼠肠道中证明的利托西汀的抗心律失常活性，在浓度大于1 microM 时在大鼠离体食道肌肉粘膜中发挥了作用。 Litoxetine HCl 的5-HT 释放作用可以解释利托西汀对未处理的大鼠组织中的5-HT 诱导的松弛的效力，这种效力被pCPA 处理所逆转。

Saterinone 是一种强效且具有选择性的磷酸二酯酶III 抑制剂，是血管α - 1-肾上腺素受体的有效拮抗剂。Saterinone 具有血管舒张作用，可用于慢性心力衰竭的急性治疗。Saterinone 对豚鼠右心室匀浆中粗cAMP 磷酸二酯酶(PDE)活性具有抑制作用，ic50值为2.3 × 10(-5) mol/l。

Methyl eugenol (4-allylveratrole) 是一种苯丙类化合物，存在于植物叶子、果实、根茎中，当植物相应的部位因食草动物进食而受损时，就会释放。它可用于消灭雄性东方果蝇。

P2X3 antagonist 34 是一种对P2X3同型三聚体受体具有高效性、选择性和口服活性的拮抗剂，其IC50值针对人类P2X3、大鼠P2X3及豚鼠P2X3分别为25 nM、92 nM和126 nM。相比之下，该化合物对人类、大鼠和豚鼠的P2X2/3异三聚体受体展现低活性。P2X3 antagonist 34 显著具有抗咳功效，同时不会影响味觉。

Glycolic acid oxidase inhibitor 1（compound 2 in table 1）是一种乙醇酸氧化酶 (glycolate oxidase) 抑制剂,从而减少肾结石的形成风险。还能够抑制由过敏反应引起的慢反应物质（SRS-A）引起的豚鼠回肠收缩，对过敏性疾病，如哮喘，具有治疗潜力。

MF63 is a selective mPGES-1 inhibitor (IC50: 0.9 nM and 1.3 nM for pig mPGES-1 and human mPGES-1 enzyme, respectively).

AGU654 (Compound 44) 是一种效力强的mPGES-1选择性抑制剂，对mPGES-1的IC50值为2.9 nM。通过抑制mPGES-1，AGU654 阻断COX-1/2将花生四烯酸转化为前列腺素E2 (PGE2) 的通路，从而有效缓解炎症、疼痛及发热。在活化的人单核细胞衍生巨噬细胞和人全血模型中，AGU654 能选择性抑制细菌外毒素诱导的PGE2生成，同时不影响其他前列腺素的产生。在豚鼠模型中，它显著减轻了发热、炎症和炎症性疼痛，展现出显著的抗炎、镇痛和退热功效。AGU654 有潜力成为研究炎症性疾病和疼痛的新方法。

BKCa activator-1 (Compound 51b) 是一种口服生物有效的 BKCa 激活剂，EC50 值为 2.82 μM。它通过增加 K+ 外流引起细胞膜超极化，抑制平滑肌收缩。在自发性高血压大鼠 (SHR) 模型中，该化合物可缓解尿失禁，并在豚鼠咳嗽模型中显示出镇咳效果。

TFC-007 是一种具有选择性和高效性的造血前列腺素 D 合成酶 (H-PGDS) 抑制剂，抑制炎症因子，可用于合成 H-PGDS 降解诱导剂 PROTAC (H-PGDS) -1 和研究雪松花粉诱导的豚鼠过敏性鼻炎。

ZD 7155 hydrochloride is a potent and selective competitive antagonist for the angiotensin II type 1 (AT1) receptor. It displaces [125I]-angiotensin II binding in guinea pig adrenal gland membranes with an IC50 value of 3.8 nM.

14S(15R)-EET is an oxylipin and a cytochrome P450 metabolite of arachidonic acid .114S(15R)-EET binds to isolated guinea pig monocytes with a Kivalue of 612.5 nM in a competitive binding assay using [3H]14(15)-EET.2It induces dilation of precontracted isolated canine epicardial arterioles (EC50= 4 pM) and denuded porcine subepicardial arterioles (EC50= 3 pM).3Unlike 14R(15S)-EET, 14S(15R)-EET does not inhibit COX in enzyme assays or isolated platelets.4 1.Daikh, B.E., Lasker, J.M., Raucy, J.L., et al.Regio- and stereoselective epoxidation of arachidonic acid by human cytochromes P450 2C8 and 2C91J. Pharmacol. Exp. Ther.271(3)1427-1433(1994) 2.Wong, P.Y.-K., Lai, P.-S., and Falck, J.R.Mechanism and signal transduction of 14 (R), 15 (S)-epoxyeicosatrienoic acid (14,15-EET) binding in guinea pig monocytesProstaglandins Other Lipid Mediat.62(4)321-333(2000) 3.Zhang, Y., Oltman, C.L., Lu, T., et al.EET homologs potently dilate coronary microvessels and activate BKCa channelsAm. J. Physiol. Heart Circ. Physiol.280(6)H2430-H2440(2001) 4.Fitzpatrick, F.A., Ennis, M.D., Baze, M.E., et al.Inhibition of cyclooxygenase activity and platelet aggregation by epoxyeicosatrienoic acidsJ. Biol. Chem.261(2)15334-15338(1986)

Arecaidine propargyl ester is an agonist of M2muscarinic acetylcholine receptors (mAChRs).1It selectively binds to M2over M1, M3, M4, and M5mAChRs in CHO cells expressing the human receptors (Kis = 0.0871, 1.23, 0.851, 0.977, and 0.933 μM, respectively). Arecaidine propargyl ester induces contractions in isolated guinea pig atrium (pD2= 8.67). It induces apoptosis and the production of reactive oxygen species (ROS) in U87 and U251 glioblastoma cells when used at a concentration of 100 μM.2Arecaidine propargyl ester decreases mean arterial blood pressure in normotensive cats (ED25= 1.9 nmol/kg).3It is toxic to house flies (Musca) when administered at a dose of 75 μg/fly.4 1.Scapecchi, S., Matucci, R., Bellucci, C., et al.Highly chiral muscarinic ligands: the discovery of (2S,2’R,3’S,5’R)-1-methyl-2-(2-methyl-1,3-oxathiolan-5-yl)pyrrolidine 3-sulfoxide methyl iodide, a potent, functionally selective, M2 partial agonistJ. Med. Chem.49(6)1925-1931(2006) 2.Di Bari, M., Tombolillo, B., Conte, C., et al.Cytotoxic and genotoxic effects mediated by M2 muscarinic receptor activation in human glioblastoma cellsNeurochem. Int.90261-270(2015) 3.Porsius, A.J., and Van Zwieten, P.A.Central action of some cholinergic drugs (arecaidine esters) and nicotine on blood pressure and heart rate of catsProg. Brain Res.47131-135(1977) 4.Honda, H., Tomizawa, M., and Casida, J.E.Insect muscarinic acetylcholine receptor: Pharmacological and toxicological profiles of antagonists and agonistsJ. Agric. Food Chem.55(6)2276-2281(2007)

Rupatadine(UR-12592,卢帕他定)是一种有效和可口服的PAF和组胺H1受体的双重拮抗剂，Ki 值分别为 0.55 μM 和 0.1 μM，能够缓解过敏症状并抗炎，可用于过敏性鼻炎和慢性荨麻疹。

Thrombin receptor agonist peptide (TRAP-14) is a 14-amino acid peptide agonist of the α-thrombin receptor. It induces aggregation of washed platelets as well as platelets in citrated and hirudin plasma. TRAP-14 (100 μM) increases the cytosolic calcium concentration in isolated guinea pig pulmonary smooth muscle cells 5-fold over baseline. It increases pulmonary arterial pressure in isolated guinea pig lung when used at a concentration of 1 μM, which is comparable to the effect induced by 10 nM α-thrombin. TRAP-14 also induces contraction of isolated rat aortic rings and increases endothelin-1 (ET-1) levels in a dose-dependent manner, an effect that is reversed by the ETA antagonist BQ-123 and the nitric oxide synthase (NOS) inhibitor L-NNA .

CCK (27-33) is a C-terminal fragment of CCK , a peptide hormone found in the intestine and brain that stimulates digestion, mediates satiety, and is involved in anxiety. Non-sulfated CCK (27-33) inhibits binding of [3H]naloxone in rat cerebellum membranes (IC50 = 4 uM) and inhibits electrically-stimulated contraction of isolated guinea pig ileum (IC50 = 17 uM), an effect that can be reversed by naloxone. Unlike sulfated CCK (27-33), the non-sulfated form does not reduce exploratory behavior in mice when administered at doses up to 1 uMol/kg.

15(S)-HEPE is a monohydroxy fatty acid synthesized from EPA by the action of 15-LO. The biosynthesis of 15-HEPE from EPA in guinea pig epidermal enzyme preparations has been documented. 15(S)-HEPE generated by soybean lipoxygenation of EPA inhibits RBL-1 cell 5-LO with an IC50 value of 28 μM.

Pyrindolol is a bacterial metabolite that has been found inS. alboverticillatus.1It inhibits neutral β-galactosidase by 50% under acidic, but not neutral, conditions when used at a concentration of 2 μg/ml. It is selective for β-galactosidase isolated from bovine liver over β-galactosidases isolated from human, bovine, pig, and rat tissues and sialidases isolated fromC. perfringens,Streptomyces, and the H3N2 strain of influenza virus (IC50s = >250 μg/ml for all).1,2 1.Aoyagi, T., Kumagai, M., Hazato, T., et al.Pyridindolol, a new β-galactosidase inhibitor produced by actinomycetesJ. Antibiot. (Tokyo)28(7)555-557(1975) 2.Kumagai, M., Aoyagi, T., and Umezawa, H.Inhibitory activity of pyridindolol on β-galactosidaseJ. Antibiot. (Tokyo)29(7)696-703(1976)

11-trans Leukotriene C4 (11-trans LTC4) is a C-11 double bond isomer of LTC4. LTC4 undergoes slow temperature-dependent isomerization to 11-trans LTC4 during storage. 11-trans LTC4 is produced in smaller amounts relative to LTC4 in ionophore-stimulated HMC-1 cells (a human mast cell line) and equine eosinophils, but not in human neutrophils or RBL-1 cells. It is nearly equipotent with LTC4 for contraction of guinea pig parenchymal and ileum. In a radioligand binding assay using guinea pig ileum as a cysteinyl leukotriene receptor preparation, the pKis for LTC4 and 11-trans LTC4 were determined to be 6.42 and 6.58, respectively.

14-Anhydrodigitoxigenin is a cardenolide and a derivative of digitoxin.1 It reduces the activity of guinea pig heart Na+/K+-ATPase by 15% when used at a concentration of 10 μM.2

Galanin is a neuropeptide with diverse biological activities. [1][2][3][4][5] It binds to rat galanin (GAL) receptor subtypes GAL1-3 (IC50s = 0.339, 1.35, and 3.31 nM, respectively) and human GAL1-3 (IC50s = 0.288, 1.62, and 12.3 nM, respectively). [1] Galanin binds to and inhibits contraction of guinea pig gastric smooth muscle cells induced by carbachol . [2] In vivo, Galanin (6 nmol, i.c.v.) increases feeding behavior in rats and increases latency to hindpaw withdrawal in response to heat and mechanical stimulation in a rat model of carrageenin-induced inflammation when administered at a dose of 2 nmol injected into the nucleus accumbens.[3][4] Galanin (5 μg, i.c.v.) also inhibits acetylcholine release induced by scopolamine in the ventral hippocampus of freely moving rats. [5]

Methoctramine is a selective antagonist of M2 muscarinic acetylcholine receptors (IC50 = 6.1 nM in CHO-K1 cell membranes).[1] It is selective for M2 over M1, M3, M4, and M5 receptors (IC50s = 92, 770, 260, and 217 nM, respectively). In vitro, methoctramine inhibits acetylcholine-induced reductions in isolated guinea pig tracheal tube contractions when used at a concentration of 1 μM.[2] In vivo, methoctramine inhibits bradycardia and bronchoconstriction induced by acetylcholinein guinea pigs with ED50 values of 38 and 81 nmol/kg, respectively. In a rat model of spinal cord injury, methoctramine suppresses bladder overactivity induced by the non-selective muscarinic acetylcholine receptor agonist oxotremorine M.[3]

17-phenyl trinor PGE2 ethyl amide is derived from 17-phenyl trinor PGE2, a synthetic analog of PGE2 that acts as an agonist of EP1 and EP3 receptors in mice (Ki = 14 and 3.7 nM, respectively) and EP1, EP3, and EP4 in rats (Ki = 25, 4.3, and 54 nM, respectively). 17-phenyl trinor PGE2 causes contraction of guinea pig ileum at a concentration of 11 μM and is 4.4 times more potent than PGE2 as an antifertility agent in hamsters. Modification of the C-1 carboxyl group to an ethyl amide serves to increase lipid solubility, thereby improving uptake into tissues and further lowering the effective concentration. Ethyl amide groups are then removed by amidases, regenerating the active free acid.

Betamethasone 21-phosphate is a synthetic glucocorticoid.1It prevents increases in macrophage and eosinophil numbers in bronchoalveolar lavage fluid (BALF) and decreases in blood leukocyte numbers in a guinea pig model of parainfluenza-3 viral infection when administered at a dose of 8 mg/kg but does not prevent airway hyperresponsiveness after infection.2Betamethasone 21-phosphate inhibits cell infiltration into the aqueous humor in a rat model of endotoxin-induced uveitis when administered topically or subcutaneously at doses of 0.01-1% or 1 mg/kg, respectively.3It increases maximal lung pressure volume curves in fetal sheep when administered to pregnant ewes at 0.75 gestation at doses of 80 and 170 μg/kg.1Betamethasone 21-phosphate increases body weight, impairs learning and memory, increases anxiolytic behavior, and reduces hippocampal neurogenesis in CD-1 mice but reduces body weight and increases neurogenesis with no effect on anxiety in high-anxiety DBA/2 mice when administered at a dose of approximately 25 mg/kg per day in the drinking water for seven weeks.4Formulations containing betamethasone 12-phosphate and betamethasone acetate have been used in the treatment of severe allergic conditions and a variety of immune-related conditions. 1.Loehle, M., Schwab, M., Kadner, S., et al.Dose-response effects of betamethasone on maturation of the fetal sheep lungAm. J. Obstet. Gynecol.202(2)186.e181-186.e187(2010) 2.Leusink-Muis, A., Ten Broeke, R., Folkerts, G., et al.Betamethasone prevents virus-induced airway inflammation but not airway hyperresponsiveness in guinea pigsClin. Exp. Allergy29(Suppl. 2)82-85(1999) 3.Tsuji, F., Sawa, K., Kato, M., et al.The effects of betamethasone derivatives on endotoxin-induced uveitis in ratExp. Eye Res.64(1)31-36(1997) 4.Aiello, R., Crupi, R., Leo, A., et al.Long-term betamethasone 21-phosphate disodium treatment has distinct effects in CD1 and DBA/2 mice on animal behavior accompanied by opposite effects on neurogenesisBehav. Brain Res.278155-166(2015)