| Size | Price | Stock | Qty |
|---|---|---|---|
| 10mg |
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| 50mg |
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| 100mg |
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| Other Sizes |
| Targets |
Complement component C5a receptor (C5aR/CD88)
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|---|---|
| ln Vitro |
Through activation of G-protein-coupled cell surface C5aR, the complement activation product C5a is known to attract and activate microglia and astrocytes in vitro. The MTT technique 24-hour plate revealed substantial differences between each group and the negative control group. Values were reported for the EP54 group between 0.02724 and 0.1748, the PMX 205 (PMX205) group between 0.09893 and 0.2465, and the tamoxifen group between 0.09880 and 0.2464. Only two groups—PMX 205 and Tamoxifen—showed significant outcomes for the 48-hour incubation time plates. The values that were recorded varied from 0.5777 to 0.8551 and 0.04987 to 0.3273, respectively. Only one group—the antagonist group, PMX 205—showed significant results on the 72-hour plates; its values ranged from 0.02136 to 0.5322 [1].
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| ln Vivo |
PMX 205, sometimes known as PMX205, is a selective and active oral C5aR antagonist. When compared to rats given with a vehicle, animals treated with PMX 205 (1 mg/kg/day, p.o.) exhibited significantly longer survival times and lower terminal motor scores. In the lumbar spinal cord, mice treated with PMX 205 also displayed decreased levels of astrocyte growth. Oral administration of PMX 205 (1 mg/kg/day) was administered to SOD1G93A rats twice, on day 28 and day 70, prior to the development of significant clinical signs. There was no discernible difference in the survival times between the two treatment regimens [2], with both treatment groups showing considerably longer survival times than untreated rats (p=0.022, day 28; p=0.015, day 70). Between the ages of 12 and 15 months (n = 17), Tg2576 mice were given a 20 μg/mL dose of PMX 205 (PMX205) in their drinking water, at which time their amyloid deposits were rapidly accumulating. inside the range. Eleven untreated Tg2576 animals served as the controls. Compared to untreated animals, PMX 205-treated animals had a notably lower fibrous plaque burden (thioflavin response) after three months. In 3×Tg mice, PMX 205 likewise markedly decreased hyperphosphorylated tau (69%) [3].
PMX205 treatment (1 mg/kg/day, oral) in SOD1G93A transgenic rats significantly extended survival time (p=0.022 for day 28 start; p=0.015 for day 70 start) and reduced end-stage motor deficit scores (p=0.002 for day 28; p=0.011 for day 70) compared with untreated rats. PMX205 also significantly delayed disease onset (defined by initial body weight loss: p=0.035 for day 28; p=0.011 for day 70) and motor symptom onset (p=0.019 for day 28; p=0.008 for day 70). The time from disease onset to motor symptom onset was extended by 4-7 days. At end-stage, PMX205-treated rats showed a 47% reduction in astrocyte immunolabeling (GFAP) in the lumbar spinal cord compared with untreated SOD1G93A rats (p=0.044, n=5), but no reduction in microglial proliferation (Iba1, p=0.68). Motor scores at euthanasia were reduced by up to 40% in treated rats. [2] |
| Enzyme Assay |
PMX205 treatment from day 28 or day 70 (1 mg/kg/day) in SOD1G93A rats resulted in significant extension of survival (Kaplan-Meier, log rank test). Terminal motor scores (combined hind limb deficits, gait, and righting reflex) were significantly lower in treated groups compared to untreated. Disease onset (age at peak body weight) and motor-deficit onset (motor score ≥2) were delayed. Disease duration and motor-deficit duration were prolonged in treated groups. No significant differences were observed between the two treatment initiation time points. [2]
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| ADME/Pharmacokinetics |
PMX205 was administered orally via drinking water at a dose of 1 mg/kg/day, starting from either day 28 or day 70 of age, continuing until the ethical endpoint (euthanasia). Control animals received water only. End-stage was defined as when rats reached a maximal righting reflex score (score = 12) or lost >20% of their peak body weight. Disease onset was determined by initial loss of body weight (age of peak body weight), and motor onset was defined as a motor score of 2 or above. Motor function was assessed using a modified motor scale scoring hind limb movement deficits (0-3 per limb), gait abnormalities (0-2), and righting reflex (0-4), with a maximal total score of 12. Rats displaying forelimb paralysis phenotype (~25% of animals) were excluded from the study to avoid confounding variables. [2]
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| References |
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| Additional Infomation |
PMX-205 is a homocyclic peptide formed by the condensation of the carboxyl group of N(2)-(3-phenylpropionyl)-L-ornithine-L-proline-3-cyclohexyl-D-alanyl-L-tryptophanyl-L-arginine with the 5-amino group of the N(2)-acylornithine residue. It exhibits antagonistic, anti-inflammatory, and C5a receptor antagonistic activity. It is a nitrogen-containing macrocyclic compound and a homocyclic peptide.
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| Molecular Formula |
C45H62N10O6
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|---|---|
| Molecular Weight |
839.055
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| Exact Mass |
838.485
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| CAS # |
514814-49-4
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| Related CAS # |
PMX 205 Trifluoroacetate
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| PubChem CID |
6918845
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| Appearance |
Typically exists as solid at room temperature
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| LogP |
5.252
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| Hydrogen Bond Donor Count |
8
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
12
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| Heavy Atom Count |
61
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| Complexity |
1530
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| Defined Atom Stereocenter Count |
5
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| SMILES |
O=C1[C@@H]2CCCN2C([C@H](CCCNC([C@H](CCC/N=C(\N)/N)NC([C@H](CC2=CNC3C=CC=CC2=3)NC([C@@H](CC2CCCCC2)N1)=O)=O)=O)NC(CCC1C=CC=CC=1)=O)=O
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| InChi Key |
VATFHFJULBPYLM-ILOBPARPSA-N
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| InChi Code |
InChI=1S/C45H62N10O6/c46-45(47)49-24-9-18-34-40(57)48-23-10-19-35(51-39(56)22-21-29-12-3-1-4-13-29)44(61)55-25-11-20-38(55)43(60)54-36(26-30-14-5-2-6-15-30)41(58)53-37(42(59)52-34)27-31-28-50-33-17-8-7-16-32(31)33/h1,3-4,7-8,12-13,16-17,28,30,34-38,50H,2,5-6,9-11,14-15,18-27H2,(H,48,57)(H,51,56)(H,52,59)(H,53,58)(H,54,60)(H4,46,47,49)/t34-,35-,36+,37-,38-/m0/s1
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| Chemical Name |
N-((3R,6S,9S,15S,20aS)-6-((1H-indol-3-yl)methyl)-3-(cyclohexylmethyl)-9-(3-guanidinopropyl)-1,4,7,10,16-pentaoxoicosahydropyrrolo[1,2-a][1,4,7,10,13]pentaazacyclooctadecin-15-yl)-3-phenylpropanamide
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| Synonyms |
PMX-205 PMX 205PMX205
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.1918 mL | 5.9590 mL | 11.9181 mL | |
| 5 mM | 0.2384 mL | 1.1918 mL | 2.3836 mL | |
| 10 mM | 0.1192 mL | 0.5959 mL | 1.1918 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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