PD123319 (Synonyms: (S)-(+)-PD 123319) |
| رقم الكتالوجGC16394 |
PD123319 (ditrifluoroacetate) هو مضاد لمستقبلات AT2 أنجيوتنسين II فعال وانتقائي مع IC50 من 34 نانومتر.
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 130663-39-7
Sample solution is provided at 25 µL, 10mM.
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PD123319 is a non-peptide inhibitor of angiotensin II receptor with IC50 value of 34nM [1].
PD123319 is an antagonist of angiotensin II receptor, unlike previous drugs act as inhibitors of the formation of Ang II. PD123319 shows inhibition potency in both rat adrenal and brain binding assay with IC50 values of 34nM and 210nM, respectively. It is found to prevent Ang II from binding the bovine zona glomerulosa microsomal preparation with IC50 value of 6.9nM in the binding assay using microsome. [2,3]. PD123319 inhibited AT2 amplification product from rat pheochromocytoma cells (PC12w) binding to 0.5 nM 125I-[Sar1, Ile8]-Ang II with IC50 values of 1.7±0.2 nM [4] .In addition, it is reported that administration of PD123319 can suppress the generation of cyclic guanosine monophosphate and increase the production of prostaglandin E2[2,3].
PD123319 was transfused intra-brachial arterial in healthy young volunteers to investigated forearm vascular responses and systemic blood pressure responses. There are significant increases in mean arterial pressure were observed during intra-brachial arterial infusions of PD123319 (p = 0.003) during both placebo (80±9 to 92±17 mmHg) and telmisartan (80±11 to 90±14 mmHg) therapy, possibly in locations other than the forearm resistance vessels. Intra-brachial arterial infusion of PD123319 (10 μg/min) has significant systemic effects on rising mean arterial pressure [5].
References:
[1] Blankley C J, Hodges J C, Klutchko S R, et al. Synthesis and structure-activity relationships of a novel series of non-peptide angiotensin II receptor binding inhibitors specific for the AT2 subtype. Journal of medicinal chemistry, 1991, 34(11): 3248-3260.
[2] Boulay G, Servant G, Luong T T, et al. Modulation of angiotensin II binding affinity by allosteric interaction of polyvinyl sulfate with an intracellular domain of the DuP-753-sensitive angiotensin II receptor of bovine adrenal glomerulosa. Molecular pharmacology, 1992, 41(4): 809-815.
[3] Siragy H. Angiotensin II receptor blockers: review of the binding characteristics. The American journal of cardiology, 1999, 84(10): 3-8.
[4] Kambayashi, Y., Takahashi, K., Bardhan, S. et al. Molecular structure and function of angiotensin type2 receptor, Kidney Inr, 1994, 46, 1502- 1504.
[5] Daugherty A, Rateri DL, Howatt DA, Charnigo R, Cassis LA. PD123319 augments angiotensin II-induced abdominal aortic aneurysms through an AT2 receptor-independent mechanism. PLoS One. 2013; 8:e61849. doi: 10.1371/journal.pone.0061849.
| Cell experiment [1]: | |
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Cell lines |
Neuro-2aneuroblastoma cells |
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Preparation Method |
Neuro-2a cells were incubated for 24-h in a 37 °C incubator, and then treated for another 24-h with designed concentrations of PD123319. Optical density (OD) was measured at 570 nm. |
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Reaction Conditions |
100μM PD123319 for 24 hours |
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Applications |
Significant reduction in cell viability was observed when Neuro-2a cells were treated with the concentration of PD123319 (100 μM). |
| Animal experiment [2]: | |
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Animal models |
LDL receptor -/- mice that were either wild type or deficient for AT2 receptors |
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Preparation Method |
Osmotic minipumps were implanted subcutaneously to deliver saline, AngII (500 ng/kg/min), or PD123319 (3 mg/kg/d ) |
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Dosage form |
Osmotic minipump, 3 mg/kg/d |
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Applications |
PD123319 acts through an angiotensin type 2(AT2) receptor-independent mechanism in angiotensin II -induced vasoconstriction in mice. PD123319 significantly increased Ang II-induced suprarenal aortic (AAAs) independent of AT2 receptors. |
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References: [1]. Y.J. Chen, Z.M. Qian, Y. Sheng, J. Zheng, Y. Liu. Angiotensin II down-regulates transferrin receptor 1 and ferroportin 1 expression in neuro-2a cells via activation of type-1 receptor. Neurosci. Lett., 716 (2020), p. 134684, 10.1016/j.neulet.2019.134684 [2]. Daugherty A, Rateri DL, Howatt DA, Charnigo R, Cassis LA. PD123319 augments angiotensin II-induced abdominal aortic aneurysms through an AT2 receptor-independent mechanism. PLoS One. 2013; 8:e61849. doi: 10.1371/journal.pone.0061849. |
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| Cas No. | 130663-39-7 | SDF | |
| المرادفات | (S)-(+)-PD 123319 | ||
| Chemical Name | (6S)-1-[[4-(dimethylamino)-3-methylphenyl]methyl]-5-(2,2-diphenylacetyl)-6,7-dihydro-4H-imidazo[4,5-c]pyridine-6-carboxylic acid | ||
| Canonical SMILES | CC1=C(C=CC(=C1)CN2C=NC3=C2CC(N(C3)C(=O)C(C4=CC=CC=C4)C5=CC=CC=C5)C(=O)O)N(C)C | ||
| Formula | C31H32N4O3 | M.Wt | 508.61 |
| الذوبان | ≥ 22.4mg/mL in DMSO, ≥ 140 mg/mL in EtOH, ≥ 104.2 mg/mL in Water | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 1.9661 mL | 9.8307 mL | 19.6614 mL |
| 5 mM | 0.3932 mL | 1.9661 mL | 3.9323 mL |
| 10 mM | 0.1966 mL | 0.9831 mL | 1.9661 mL |
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Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
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Quality Control & SDS
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- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 16 reference(s) in Google Scholar.)
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