PMX-53

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.

Product information

CAS Number: 219639-75-5

Molecular Weight: 896.09

Formula: C47H65N11O7

Chemical Name: (2S)-N-[(3R,6S,9S,15S,20aS)-3-(cyclohexylmethyl)-9-{3-[(diaminomethylidene)amino]propyl}-6-[(1H-indol-3-yl)methyl]-1,4,7,10,16-pentaoxo-icosahydropyrrolo[1,2-a]1,4,7,10,13-pentaazacyclooctadecan-15-yl]-2-acetamido-3-phenylpropanamide

Smiles: CC(=O)N[C@@H](CC1C=CC=CC=1)C(=O)N[C@H]1CCCNC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC2=CNC3=CC=CC=C23)NC(=O)[C@@H](CC2CCCCC2)NC(=O)[C@@H]2CCCN2C1=O

InChiKey: YOKBGCTZYPOSQM-HPSWDUTRSA-N

InChi: InChI=1S/C47H65N11O7/c1-29(59)53-37(25-30-13-4-2-5-14-30)42(61)55-36-20-11-22-50-41(60)35(19-10-23-51-47(48)49)54-44(63)39(27-32-28-52-34-18-9-8-17-33(32)34)56-43(62)38(26-31-15-6-3-7-16-31)57-45(64)40-21-12-24-58(40)46(36)65/h2,4-5,8-9,13-14,17-18,28,31,35-40,52H,3,6-7,10-12,15-16,19-27H2,1H3,(H,50,60)(H,53,59)(H,54,63)(H,55,61)(H,56,62)(H,57,64)(H4,48,49,51)/t35-,36-,37-,38+,39-,40-/m0/s1

Technical Data

Appearance: Solid Power

Purity: ≥98% (or refer to the Certificate of Analysis)

Solubility: DMSO : 125 mg/mL (139.49 mM; Need ultrasonic).

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥12 months if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined

HS Tariff Code: 382200

How to use

In Vitro:

PMX-53 is a potent CD88 antagonist and inhibits C5a-induced neutrophil myeloperoxidase release and chemotaxis with IC50 values of 22 nM and 75 nM, respectively. PMX-53 (10 nM) inhibits C5a-induced Ca2+ mobilization in HMC-1 cells, but at higher concentrations( ≥30 nM) it causes degranulation in LAD2 mast cells, CD34+ cell-derived mast cells, and RBL-2H3 cells stably expressing MrgX2. Replacement of Trp with Ala and Arg with dArg abolishes the ability of PMX-53 to inhibit C5a-induced Ca2+ mobilization in HMC-1 cells and to cause degranulation in RBL-2H3 cells expressing MrgX2.

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. Local pretreatment of rats with PMX-53 (60-180 μg per paw) inhibits zymosan-, carrageenan-, lipopolysaccharide (LPS)- and antigen-induced hypernociception. 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 beingreached within 20 min The plasma elimination half-life wasapproximately 70 min in this case. 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.

Products are for research use only. Not for human use.