| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
Complement factor C3 (and its activated form C3b). POT-4 binds to C3 and C3b, preventing the cleavage of C3 by C3 convertases. By blocking this central amplification step, POT-4 inhibits activation of all three complement pathways (classical, lectin, and alternative), thereby reducing the production of downstream effectors such as C5a and the membrane attack complex (MAC).
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| ln Vitro |
POT-4 is a cyclic peptide that demonstrates binding ability to C3, blocking cleavage to its active parts, C3a and C3b. It is a derivative of compstatin, a powerful C3 inhibitor[2].
In vitro, POT-4 binds to human complement factor C3 with high affinity, inhibiting the formation of C3 convertases and blocking the activation of the complement cascade at the central C3 activation step. It prevents the cleavage of C3 into C3a and C3b, thereby effectively inhibiting complement activation in a dose-dependent manner with an IC50 in the low nanomolar range. |
| ln Vivo |
No detailed in vivo studies are reported for POT-4 alone; however, its parent compound Compstatin has demonstrated efficacy in animal models of complement-mediated diseases. POT-4 was developed for intravitreal administration in age-related macular degeneration, where it is expected to reduce local complement activation and inflammation in the retina.
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| Enzyme Assay |
A direct binding ELISA or surface plasmon resonance (SPR) is used to assess C3 binding. Recombinant human C3 is immobilized on a microplate or sensor chip, and serially diluted POT-4 (0.1-1000 nM) is added. For SPR, the Kd is calculated from association/dissociation rates. For functional inhibition, a complement hemolysis assay is performed: sensitized sheep erythrocytes are incubated with human complement serum in the presence of POT-4. Inhibition of hemolysis is measured at 415 nm.
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| Cell Assay |
For in vitro cellular assays, human whole blood or serum is used to assess complement activation. Blood is treated with POT-4 (0.01-100 uM) and then stimulated with complement activators (e.g., zymosan, LPS, or immune complexes). Complement activation products, such as C3a, C5a, C5b-9 (MAC), and factor Bb, are measured in plasma by ELISA or multiplex assay. Inhibition of C3b deposition on surfaces is assessed by ELISA.
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| Animal Protocol |
No published in vivo studies are available for POT-4. For research use, a mouse model of choroidal neovascularization (CNV) or laser-induced CNV can be used to model AMD. POT-4 is administered by intravitreal injection at doses of 10-100 ug per eye. Fundus photography and fluorescein angiography are performed to assess neovascularization. Retinal tissues are harvested for histopathological analysis and for measurement of complement activation markers (C3, MAC) by immunofluorescence.
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| ADME/Pharmacokinetics |
POT-4 has a molecular weight of 1627.85 g/mol and a formula of C72H102N22O18S2. It is a cyclic peptide soluble in DMSO (90 mg/mL) and water (30 mg/mL). As a peptide, it has poor oral bioavailability and is administered intravitreally or intravenously for research. The plasma half-life is short (minutes to hours) due to rapid clearance and proteolytic degradation.
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| Toxicity/Toxicokinetics |
Detailed toxicological data for POT-4 are not publicly available. In preclinical studies, Compstatin derivatives have been generally well-tolerated with no significant systemic toxicity reported. Intravitreal administration may cause mild, transient ocular inflammation. There is a theoretical risk of increased susceptibility to infections due to complement inhibition.
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| References | |
| Additional Infomation |
POT-4 (AL-78898A) has been investigated in clinical trials for the treatment of age-related macular degeneration (AMD). It has not received regulatory approval for any indication. This research-grade cyclic peptide is available for laboratory studies to investigate the role of complement factor C3 in complement-mediated diseases, including AMD, paroxysmal nocturnal hemoglobinuria (PNH), and other inflammatory conditions.
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| Molecular Formula |
C72H102N22O18S2
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|---|---|
| Molecular Weight |
1627.84689188004
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| Exact Mass |
1626.718
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| CAS # |
934461-40-2
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| Related CAS # |
POT-4 TFA
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| PubChem CID |
16158103
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| Appearance |
White to off-white solid powder
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| LogP |
-2.9
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| Hydrogen Bond Donor Count |
22
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| Hydrogen Bond Acceptor Count |
22
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| Rotatable Bond Count |
26
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| Heavy Atom Count |
114
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| Complexity |
3420
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| Defined Atom Stereocenter Count |
14
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| SMILES |
S1C[C@@H](C(N[C@H](C(N[C@H](C(N[C@H](C(N[C@@H](CC(=O)O)C(N[C@H](C(NCC(N[C@@H](C)C(N[C@@H](CC2=CNC=N2)C(N[C@H](C(N[C@H](C(N[C@H](C(N)=O)[C@@H](C)O)=O)CS1)=O)CCCNC(=N)N)=O)=O)=O)=O)CC1=CNC2C=CC=CC1=2)=O)=O)CCC(N)=O)=O)CC1=CN(C)C2C=CC=CC1=2)=O)C(C)C)=O)NC([C@H]([C@@H](C)CC)NC(C)=O)=O
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| InChi Key |
WMEMLXDTLKSUOD-OGCOPIPOSA-N
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| InChi Code |
InChI=1S/C72H102N22O18S2/c1-9-35(4)58(83-38(7)96)71(112)91-52-32-114-113-31-51(69(110)93-59(37(6)95)60(74)101)90-63(104)45(18-14-22-78-72(75)76)84-66(107)49(25-41-28-77-33-81-41)86-61(102)36(5)82-55(98)29-80-62(103)47(23-39-27-79-44-17-12-10-15-42(39)44)87-67(108)50(26-56(99)100)88-64(105)46(20-21-54(73)97)85-65(106)48(89-70(111)57(34(2)3)92-68(52)109)24-40-30-94(8)53-19-13-11-16-43(40)53/h10-13,15-17,19,27-28,30,33-37,45-52,57-59,79,95H,9,14,18,20-26,29,31-32H2,1-8H3,(H2,73,97)(H2,74,101)(H,77,81)(H,80,103)(H,82,98)(H,83,96)(H,84,107)(H,85,106)(H,86,102)(H,87,108)(H,88,105)(H,89,111)(H,90,104)(H,91,112)(H,92,109)(H,93,110)(H,99,100)(H4,75,76,78)/t35-,36-,37+,45-,46-,47-,48-,49-,50-,51-,52-,57-,58-,59-/m0/s1
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| Chemical Name |
2-[(4R,7S,10S,13S,19S,22S,25S,28S,31S,34R)-34-[[(2S,3S)-2-acetamido-3-methylpentanoyl]amino]-4-[[(2S,3R)-1-amino-3-hydroxy-1-oxobutan-2-yl]carbamoyl]-25-(3-amino-3-oxopropyl)-7-(3-carbamimidamidopropyl)-10-(1H-imidazol-4-ylmethyl)-19-(1H-indol-3-ylmethyl)-13-methyl-28-[(1-methylindol-3-yl)methyl]-6,9,12,15,18,21,24,27,30,33-decaoxo-31-propan-2-yl-1,2-dithia-5,8,11,14,17,20,23,26,29,32-decazacyclopentatriacont-22-yl]acetic acid
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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 Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
| 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) |
DMSO: 100 mg/mL (61.43 mM)
H2O: 50 mg/mL (30.72 mM) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (1.54 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: 2.5 mg/mL (1.54 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (1.54 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 0.6143 mL | 3.0715 mL | 6.1431 mL | |
| 5 mM | 0.1229 mL | 0.6143 mL | 1.2286 mL | |
| 10 mM | 0.0614 mL | 0.3072 mL | 0.6143 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.
Link: https://clinicaltrials.gov/ct2/show/NCT01603043
Conditions:Geographic AtrophyLink: https://clinicaltrials.gov/ct2/show/NCT01157065
Conditions:Exudative Age-Related Macular DegenerationProducts are for research use only; We do not sell to patients
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