| Identification | Back Directory | [Name]
PMX 53 | [CAS]
219639-75-5 | [Synonyms]
Ac-Phe-cyclo(Orn-Pro-D-Cha-Trp-Arg)
L-Arginine, N-acetyl-L-phenylalanyl-L-ornithyl-L-prolyl-3-cyclohexyl-D-alanyl-L-tryptophyl-, (6→2)-lactam | [Molecular Formula]
C47H65N11O7 | [MDL Number]
MFCD07363866 | [MOL File]
219639-75-5.mol | [Molecular Weight]
896.11 |
| Chemical Properties | Back Directory | [density ]
1.40±0.1 g/cm3(Predicted) | [storage temp. ]
Store at -20°C, protect from light, stored under nitrogen | [solubility ]
Soluble in DMSO | [form ]
Solid | [pka]
13.23±0.70(Predicted) | [color ]
White to off-white | [Water Solubility ]
Soluble to 2 mg/ml in water | [Sequence]
Ac-Phe-{Orn}-Pro-{dCha}-Trp-Arg (Lactam bridge: Orn2-Arg6) |
| Hazard Information | Back Directory | [Uses]
PMX-53 (3D53) is a synthetic peptidic and a potent and orally active complement C5a receptor (CD88) antagonist with an IC50 of 20 nM. PMX-53 is also a low-affinity MrgX2 agonist that stimulates MrgX2-mediated mast cell degranulation. PMX-53 specifically binds to C5aR1 and does not bind to the second C5aR (C5L2) and C3aR. PMX-53 has anti-inflammatory, anticancer and antiatherosclerotic effects[1][2][3][4][5][6]. | [Biological Activity]
Cell permeable: yes''Primary Target
C5aR''Reversible: yes | [in vivo]
PMX-53 (0.3-3 mg/kg; subcutaneous injection; once; male Wistar rats) treatment inhibits the hypernociception induced by zymosan-activated serum and C5a but not by the direct-acting hypernociceptive mediators, prostaglandin E2 and dopamine[2].
Local pretreatment of rats with PMX-53 (60-180 μg per paw) inhibits zymosan-, carrageenan-, lipopolysaccharide (LPS)- and antigen-induced hypernociception[2].
Pharmacokinetic analyses have shown that PMX-53 (3D53) appears in the plasma within 5 min of oral administration (3 mg/kg) to rats, with peak blood levels of approximately 0.3 μM being reached within 20 min The plasma elimination half-life was approximately 70 min in this case[3].
The non-acetylated version of PMX-53 (3D53) binds to isolated mouse neutrophils with a Kd value of 30 nM (mouse C5a binds with a Kd value of 0.3 nM) and inhibits mouse C5a-induced chemotaxis with an IC50 value of 0.5 nM[3]. | Animal Model: | Adult male Wistar rats (weighing 180-200?g) injected with zymosan[2] | | Dosage: | 0.3 mg/kg, 1 mg/kg or 3?mg/kg | | Administration: | Subcutaneous injection; once | | Result: | Inhibited the hypernociception induced by zymosan-activated serum and C5a.
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| [storage]
Store at -20°C | [References]
[1] Subramanian H, et al. PMX-53 as a dual CD88 antagonist and an agonist for Mas-related gene 2 (MrgX2) in human mast cells. Mol Pharmacol. 2011 Jun;79(6):1005-13. DOI:10.1124/mol.111.071472
[2] Ting E, et al. Role of complement C5a in mechanical inflammatory hypernociception: potential use of C5a receptor antagonists to control inflammatory pain. Br J Pharmacol. 2008 Mar;153(5):1043-53. DOI:10.1038/sj.bjp.0707640
[3] Holland MC, et al. Synthetic small-molecule complement inhibitors. Curr Opin Investig Drugs. 2004 Nov;5(11):1164-73. PMID:15573867
[4] Finch AM, et al. Low-molecular-weight peptidic and cyclic antagonists of the receptor for the complement factor C5a. J Med Chem. 1999 Jun 3;42(11):1965-74. DOI:10.1021/jm9806594
[5] Manthey HD, et al. Complement C5a inhibition reduces atherosclerosis in ApoE-/- mice. FASEB J. 2011 Jul;25(7):2447-55. DOI:10.1096/fj.10-174284
[6] Vadrevu SK, et al. Complement c5a receptor facilitates cancer metastasis by altering T-cell responses in the metastatic niche. Cancer Res. 2014 Jul 1;74(13):3454-65. DOI:10.1158/0008-5472.CAN-14-0157 |
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BOC Sciences
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https://www.bocsci.com |
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