| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
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| Other Sizes |
| Targets |
Complement factor D (FD; CFD). Vemircopan is a selective, orally active inhibitor of factor D, a serine protease that cleaves complement factor B into Ba and Bb, an essential step in the alternative pathway (AP) activation. By inhibiting FD, it blocks the formation of the alternative pathway C3 convertase (C3bBb), thereby preventing downstream complement activation and MAC formation.
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| ln Vitro |
In vitro, vemircopan binds to complement factor D (FD) with high affinity and potently inhibits FD enzymatic activity. At low nanomolar concentrations, it effectively blocks alternative pathway-mediated hemolysis and complement component C3 deposition on target cells. It also inhibits AP-induced formation of the membrane attack complex (MAC) in human whole blood assays.
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| ln Vivo |
In vivo, vemircopan has demonstrated efficacy in preclinical models of complement-mediated diseases. In animal models, oral administration of vemircopan reduces complement activity, decreases hemolysis, and prevents tissue damage. In Phase 2 clinical studies, vemircopan significantly reduced proteinuria in patients with IgA nephropathy and showed complement inhibition in PNH and MG patients.
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| Enzyme Assay |
A biochemical factor D enzyme activity assay is used to assess inhibition: purified human complement factor D (FD) is incubated with a fluorogenic peptide substrate (e.g., Z-Lys-SBzl) and complement factor B in the presence of serially diluted vemircopan (0.1-1000 nM). The generation of cleavage products is monitored by fluorescence spectrophotometry, and the IC50 is calculated. A Kd value is determined by SPR.
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| Cell Assay |
For in vitro hemolysis assays, human red blood cells (RBCs) from PNH patients or normal human RBCs treated with antibody to activate the alternative pathway are incubated with human complement serum in the presence of serially diluted vemircopan (0.1-1000 nM). Hemoglobin release is measured spectrophotometrically at 415 nm, and the IC50 for inhibition of hemolysis is calculated. Complement C3 deposition on RBCs is assessed by flow cytometry.
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| Animal Protocol |
The in vivo efficacy is evaluated in a mouse model of alternative pathway-mediated hemolysis (e.g., the PNH xenograft model using human RBCs in NSG mice). Vemircopan is administered orally at doses of 1-30 mg/kg. Blood samples are collected at multiple time points to measure hemolysis, RBC counts, and complement activity (e.g., by CH50 or AP50 assays). In a rat model of IgA nephropathy (IgAN), vemircopan is administered orally for 4-8 weeks, and proteinuria, hematuria, and glomerular pathology are assessed.
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| ADME/Pharmacokinetics |
Vemircopan has a molecular weight of 602.5 g/mol and a formula of C29H28BrN7O3. It is orally bioavailable with moderate half-life (in humans, approximately 6-10 hours, supporting twice-daily dosing). In animal models, Cmax is dose-proportional, and clearance is moderate. The compound is highly protein-bound (LogP 4.1) with a tPSA of 123, indicating good permeability. It is soluble in DMSO.
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| Toxicity/Toxicokinetics |
In clinical studies, vemircopan has been generally well-tolerated. The most common adverse events reported were mild-to-moderate headaches, nasopharyngitis, diarrhea, and nausea. No dose-limiting toxicities or significant safety signals have been observed at therapeutic doses. As a complement inhibitor, there is a potential increased risk of encapsulated bacterial infections, though no such cases have been reported in early trials.
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| References | |
| Additional Infomation |
Vermicolpan is an orally bioavailable inhibitor of complement factor D (FD; CFD). Complement factor D is a serine protease that cleaves complement factor B and possesses potential complement system inhibitory activity. Upon administration, Vermicolpan targets and blocks the activity of FD, thereby inhibiting the cleavage of complement factor B into complement factor Bα and complement factor β in the alternative complement cascade pathway. This inhibits FD-mediated signaling and activation of the alternative complement pathway (ACP), blocking complement-mediated hemolysis in paroxysmal nocturnal hemoglobinuria (PNH) and preventing ACP-induced tissue damage. FD plays a crucial role in ACP activation.
Vemircopan (ALXN2050) is a second-generation, oral complement factor D inhibitor that has been investigated in Phase 2 clinical trials for IgA nephropathy (IgAN), paroxysmal nocturnal hemoglobinuria (PNH), myasthenia gravis (MG), and lupus nephritis. It is not yet approved for therapeutic use and is available for research purposes to study the alternative complement pathway and evaluate factor D inhibition as a therapeutic strategy in complement-mediated diseases. |
| Molecular Formula |
C29H28BRN7O3
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|---|---|
| Molecular Weight |
602.4817
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| Exact Mass |
601.143
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| CAS # |
2086178-00-7
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| PubChem CID |
126642840
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| Appearance |
White to off-white solid powder
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| LogP |
4.1
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
40
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| Complexity |
1010
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| Defined Atom Stereocenter Count |
3
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| SMILES |
BrC1C([H])=C([H])C(C([H])([H])[H])=C(N=1)N([H])C([C@]1([H])C([H])([H])[C@@]2(C([H])([H])[H])C([H])([H])[C@@]2([H])N1C(C([H])([H])N1C2C([H])=C([H])C(C3=C([H])N=C(C([H])([H])[H])N=C3[H])=C([H])C=2C(C(C([H])([H])[H])=O)=N1)=O)=O
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| InChi Key |
OCXAGXCMZACNEC-CTWZREHQSA-N
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| InChi Code |
InChI=1S/C29H28BrN7O3/c1-15-5-8-24(30)33-27(15)34-28(40)22-10-29(4)11-23(29)37(22)25(39)14-36-21-7-6-18(19-12-31-17(3)32-13-19)9-20(21)26(35-36)16(2)38/h5-9,12-13,22-23H,10-11,14H2,1-4H3,(H,33,34,40)/t22-,23+,29-/m0/s1
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| Chemical Name |
(1R,3S,5R)-2-[2-[3-acetyl-5-(2-methylpyrimidin-5-yl)indazol-1-yl]acetyl]-N-(6-bromo-3-methylpyridin-2-yl)-5-methyl-2-azabicyclo[3.1.0]hexane-3-carboxamide
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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: 50 mg/mL (82.99 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 1 mg/mL (1.66 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 10.0 mg/mL clear DMSO stock solution to 400 μL of PEG300 and mix evenly; then add 50 μL of Tween-80 to the above solution and mix evenly; then add 450 μL of 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: ≥ 1 mg/mL (1.66 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in 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 10.0 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: ≥ 1 mg/mL (1.66 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 | 1.6598 mL | 8.2990 mL | 16.5981 mL | |
| 5 mM | 0.3320 mL | 1.6598 mL | 3.3196 mL | |
| 10 mM | 0.1660 mL | 0.8299 mL | 1.6598 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/NCT05097989
Conditions:Lupus Nephritis|Immunoglobulin A Nephropathy|IgAN|LNLink: https://clinicaltrials.gov/ct2/show/NCT06071442
Conditions:Healthy ParticipantsLink: https://clinicaltrials.gov/ct2/show/NCT05259085
Conditions:Impaired Hepatic Function|Healthy
Title:Study of ALXN2050 in Adult Participants With Generalized Myasthenia Gravis
Status:Terminated
updateDate:2025-01-09
Ctid:NCT05218096
Link: https://clinicaltrials.gov/ct2/show/NCT05218096
Conditions:Generalized Myasthenia Gravis|Myasthenia GravisLink: https://clinicaltrials.gov/ct2/show/NCT04170023
Conditions:Paroxysmal Nocturnal Hemoglobinuria (PNH)Link: https://clinicaltrials.gov/ct2/show/NCT04623710
Conditions:Renal Impairment|HealthyLink: https://clinicaltrials.gov/ct2/show/NCT05202145
Conditions:HealthyLink: https://clinicaltrials.gov/ct2/show/NCT04952545
Conditions:HealthyLink: https://clinicaltrials.gov/ct2/show/NCT04933682
Conditions:HealthyLink: https://clinicaltrials.gov/ct2/show/NCT04660890
Conditions:HealthyLink: https://clinicaltrials.gov/ct2/show/NCT05047458
Conditions:HealthyLink: https://clinicaltrials.gov/ct2/show/NCT05047484
Conditions:HealthyLink: https://clinicaltrials.gov/ct2/show/NCT04709081
Conditions:HealthyProducts are for research use only; We do not sell to patients
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