| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
The compound targets multiple pathways crucial for vascular integrity and angiogenesis. It binds integrins alphavbeta3 and alpha5beta1, inhibiting VEGF receptor signaling. Simultaneously, it acts as an activator (agonist) of the Tie2 receptor, promoting vascular stability and reducing pathological vessel leakiness and inflammation.
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| ln Vitro |
In vitro, Gersizangitide (0-100 microM) enhances the phosphorylation of Tie2 and its downstream effector Akt in microvascular endothelial cells treated with Angiopoietin-2 (Ang2), demonstrating its function as a Tie2 activator. This leads to enhanced endothelial barrier function and reduced vascular permeability in cell-based assays.
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| ln Vivo |
In vivo, intravitreal injection of Gersizangitide (1 microg) in a mouse model of oxygen-induced ischemic retinopathy enhances Tie2 phosphorylation in retinal endothelial cells, reducing neovascularization. In a uveitis mouse model induced by LPS, it inhibits vascular leakage and decreases albumin levels in the vitreous humor.
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| Enzyme Assay |
A direct non-cellular binding assay is performed using Surface Plasmon Resonance (SPR). Biotinylated integrin proteins (alphavbeta3 and alpha5beta1) are immobilized on a sensor chip. Increasing concentrations of Gersizangitide are flowed over the chip, and the binding affinity (Kd) is calculated from the association and dissociation rates. Kd values of 1.29 nM and 2.21 nM for the two integrins have been reported.
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| Cell Assay |
In vitro cellular activity is assessed in human umbilical vein endothelial cells (HUVECs). Cells are serum-starved and then treated with Ang2 to mimic a pathological state, followed by co-incubation with Gersizangitide (0-100 microM). After stimulation, cell lysates are collected and subjected to Western blotting to detect the phosphorylation levels of Tie2 and Akt. The assay quantifies the peptide‘s ability to activate the Tie2 signaling pathway.
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| Animal Protocol |
The in vivo efficacy is evaluated in a mouse model of laser-induced choroidal neovascularization (CNV), which mimics wet age-related macular degeneration (AMD). A single intravitreal injection of Gersizangitide (1 microg) is administered. After 14 days, the area of CNV is measured in flat-mounted RPE-choroid-sclera complexes stained with isolectin B4 to quantify the reduction in pathological blood vessel growth compared to vehicle control.
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| ADME/Pharmacokinetics |
Gersizangitide is a peptide and is intended for local administration to the eye (intravitreal or suprachoroidal injection) to maximize local bioavailability and minimize systemic exposure. Following injection, it is expected to be cleared slowly from the vitreous humor (half-life likely days). It would be metabolized into small peptides and amino acids via proteolytic enzymes.
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| Toxicity/Toxicokinetics |
Toxicity assessment is ongoing in clinical trials. Preliminary Phase 1/2a DISCOVER trial results indicate no significant safety concerns with suprachoroidal administration. As it is injected locally into the eye, adverse events are typically ocular (e.g., transient injection site pain, mild inflammation) and not systemic. It has not shown significant off-target toxicity in preclinical models.
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| References |
[1]. WHO Drug Information, Vol. 35, No. 4, 2021. Geneva: World Health Organization; 2022.
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| Additional Infomation |
Gersizangitide is in Phase 1/2a clinical trials (DISCOVER trial) for the treatment of neovascular age-related macular degeneration (nAMD) and diabetic macular edema (DME). Its unique dual mechanism of blocking VEGF while activating Tie2 distinguishes it from standard anti-VEGF therapies, offering the potential for better vessel stabilization and less frequent dosing. It is not yet approved for clinical use.
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| Molecular Formula |
C111H167N29O28
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|---|---|
| Molecular Weight |
2355.69120526314
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| Exact Mass |
2355.256
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| CAS # |
2417491-82-6
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| PubChem CID |
162625113
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| Appearance |
White to off-white solid powder
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| LogP |
-3.6
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| Hydrogen Bond Donor Count |
32
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| Hydrogen Bond Acceptor Count |
31
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| Rotatable Bond Count |
75
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| Heavy Atom Count |
168
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| Complexity |
5230
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| Defined Atom Stereocenter Count |
24
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| SMILES |
CC[C@H](C)[C@@H](C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC(=O)N)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC(=O)N)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N)NC(=O)[C@H](CC2=CC=CC=C2)NC(=O)[C@H](C)NC(=O)[C@H](CC3=CC=CC=C3)NC(=O)[C@@H]4CCCN4C(=O)[C@H](C)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CO)NC(=O)[C@H](CC5=CC=CC=C5)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CC(C)C)N
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| InChi Key |
YVOJSNXOGANXSQ-BZHNYRKKSA-N
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| InChi Code |
InChI=1S/C111H167N29O28/c1-14-58(8)86(105(164)132-76(52-82(114)144)98(157)129-77(53-83(145)146)100(159)135-85(57(6)7)104(163)138-88(60(10)16-3)107(166)131-75(51-81(113)143)97(156)126-71(90(115)149)47-64-32-21-17-22-33-64)137-101(160)78(54-84(147)148)133-106(165)87(59(9)15-2)136-99(158)74(50-67-38-27-20-28-39-67)127-91(150)61(11)122-95(154)72(48-65-34-23-18-24-35-65)130-103(162)80-42-31-45-140(80)109(168)62(12)123-108(167)89(63(13)142)139-102(161)79(55-141)134-96(155)73(49-66-36-25-19-26-37-66)128-94(153)70(41-30-44-121-111(118)119)125-93(152)69(40-29-43-120-110(116)117)124-92(151)68(112)46-56(4)5/h17-28,32-39,56-63,68-80,85-89,141-142H,14-16,29-31,40-55,112H2,1-13H3,(H2,113,143)(H2,114,144)(H2,115,149)(H,122,154)(H,123,167)(H,124,151)(H,125,152)(H,126,156)(H,127,150)(H,128,153)(H,129,157)(H,130,162)(H,131,166)(H,132,164)(H,133,165)(H,134,155)(H,135,159)(H,136,158)(H,137,160)(H,138,163)(H,139,161)(H,145,146)(H,147,148)(H4,116,117,120)(H4,118,119,121)/t58-,59-,60-,61-,62-,63+,68-,69-,70-,71-,72-,73-,74-,75-,76-,77-,78-,79-,80-,85-,86-,87-,88-,89-/m0/s1
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| Chemical Name |
(3S)-3-[[(2S)-4-amino-2-[[(2S,3S)-2-[[(2S)-2-[[(2S,3S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-1-[(2S)-2-[[(2S,3R)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-amino-4-methylpentanoyl]amino]-5-carbamimidamidopentanoyl]amino]-5-carbamimidamidopentanoyl]amino]-3-phenylpropanoyl]amino]-3-hydroxypropanoyl]amino]-3-hydroxybutanoyl]amino]propanoyl]pyrrolidine-2-carbonyl]amino]-3-phenylpropanoyl]amino]propanoyl]amino]-3-phenylpropanoyl]amino]-3-methylpentanoyl]amino]-3-carboxypropanoyl]amino]-3-methylpentanoyl]amino]-4-oxobutanoyl]amino]-4-[[(2S)-1-[[(2S,3S)-1-[[(2S)-4-amino-1-[[(2S)-1-amino-1-oxo-3-phenylpropan-2-yl]amino]-1,4-dioxobutan-2-yl]amino]-3-methyl-1-oxopentan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-4-oxobutanoic 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 (e.g. under nitrogen), avoid exposure to moisture and light. |
| 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) |
H2O: 33.33 mg/mL (14.15 mM)
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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 | 0.4245 mL | 2.1225 mL | 4.2450 mL | |
| 5 mM | 0.0849 mL | 0.4245 mL | 0.8490 mL | |
| 10 mM | 0.0425 mL | 0.2123 mL | 0.4245 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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