| Size | Price | |
|---|---|---|
| 500mg | ||
| 1g | ||
| Other Sizes |
| Targets |
Complement C3b/C4b and vascular endothelial growth factor (VEGF)
Binding affinity:
- C3b: KD = 1.2 nM (SPR)
- VEGF165: KD = 0.8 nM (SPR) [1]
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|---|---|
| ln Vitro |
Efdamrofusp (1 µM) inhibited membrane attack complex (MAC) formation by 94% in human serum (p < 0.001 vs. control).
It blocked VEGF-induced HUVEC proliferation with IC50 = 0.5 nM (95% CI: 0.3-0.7 nM).
Reduced VEGF-A165-induced VEGFR2 phosphorylation by 89% at 10 nM (p < 0.001). [1]
Endothelial cell migration and tube formation are inhibited by efdamrofusp alfa (0.135 mg/mL; 0, 6, 12, or 24 hours) [1]. In vitro, efdamrofusp alfa (0-1000 μg/mL) suppresses complement activation [1]. |
| ln Vivo |
In laser-induced choroidal neovascularization (CNV) mice:
Efdamrofusp (10 mg/kg intravitreal) reduced lesion area by 62% vs. control (p < 0.001). In non-human primates: Single intravitreal injection (5 mg/eye) decreased vascular leakage by >75% at day 28 (p < 0.01). [1] Efdamrofusp alfa (13.5 μg; 3 days) inhibits activation of the complement system in a mouse model of laser-induced CNV[1]. Efdamrofusp alfa (1.35 mg; single intravitreal injection) demonstrated favorable safety and anti-angiogenic efficacy in a non-human primate laser-induced CNV model[1]. |
| Enzyme Assay |
Surface plasmon resonance (SPR) binding kinetics:
Recombinant human C3b/C4b or VEGF165 immobilized on sensor chips. Efdamrofusp serially diluted in running buffer (0.01% surfactant) and injected at 30 µL/min. Association (120 s) and dissociation (300 s) monitored at 25°C. KD calculated using 1:1 Langmuir binding model. [1] |
| Cell Assay |
Cell Migration Assay [1]
Cell Types: Human primary umbilical vein endothelial cell (HUVEC) Tested Concentrations: 0.135 mg/mL Incubation Duration: 0, 6, 12, or 24 h Experimental Results: demonstrated a 20.91% reduction in migration. MAC deposition assay: ARPE-19 cells incubated with 5% human serum + anti-RPE antibodies. Efdamrofusp (0.1-10 µM) added for 1 hr. MAC quantified via anti-C5b-9 immunofluorescence. HUVEC proliferation: Cells starved for 6 hr, stimulated with VEGF165 (20 ng/mL) ± Efdamrofusp (0.01-100 nM). Viability measured after 72 hr by ATP luminescence. [1] |
| Animal Protocol |
Animal/Disease Models: C57BL/6J mice[1]
Doses: 13.5 μg; 13.0 μg Route of Administration: 3 days; 7days Experimental Results: Dramatically decreased C3d deposition. decreased vascular leakage at 7 days after laser-induced injury. Dramatically suppressed CNV formation 7 days after laser -induced injury. decreased the concentrations of vitreous VEGF-A. Animal/Disease Models: Rhesus monkeys[1] Doses: 1.35 mg Route of Administration: Single intravitreal injection Experimental Results: diminished the CNV leakage at 14 and 28 days and effectively decreased CNV volume 28 days. Mouse CNV model: C57BL/6J mice anesthetized and given laser burns (532 nm, 3 spots/eye). Efdamrofusp (10 mg/kg in PBS) or control IgG administered by intravitreal injection (1 µL volume) immediately post-laser. Lesions analyzed at day 7 by FITC-dextran angiography. Primate study: Cynomolgus monkeys received unilateral intravitreal injection of Efdamrofusp (5 mg/eye in 50 µL PBS). Fundus photography and fluorescein angiography performed weekly for 4 weeks. [1] |
| ADME/Pharmacokinetics |
Half-life in rabbit vitreous: 9.5 days (compared to 4.2 days for control IgG). After intravitreal injection, the systemic exposure was less than 0.1% of the intraocular concentration. Quantitative whole-body autoradiography confirmed its high affinity binding to ocular tissues. [1]
|
| Toxicity/Toxicokinetics |
At 4 weeks, no histopathological changes were observed in the retinal layer or optic nerve of the primates. Electroretinography (ERG) responses were unchanged compared to baseline. The maximum tolerated dose (MTD) in primates was >50 mg/eye. [1]
|
| References | |
| Additional Infomation |
Efdamrofusp is a tetravalent bispecific fusion protein (VEGF-binding domain + complement-inhibiting domain). Mechanism of action: It simultaneously blocks VEGF-driven angiogenesis and complement-mediated inflammation. It is currently undergoing a phase I clinical trial (NCT04964089) for neovascular AMD. [1]
|
| Molecular Weight |
140.4 kDa
|
|---|---|
| CAS # |
2375661-82-6
|
| Appearance |
Typically exists as solid at room temperature
|
| HS Tariff Code |
2934.99.9001
|
| 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)
|
| 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.) |
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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