| 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 |
IC50: 30 nM (Factor D)[1] Kd: 6 nM (Factor D)[1]
Complement factor D (FD; CFD). Factor D inhibitor 6 is a highly selective, orally active small-molecule antagonist of FD with an IC50 of 30 nM and a Kd of 6 nM. It binds to FD, blocking its enzymatic activity in cleaving complement factor B into Ba and Bb, thereby inhibiting the formation of the alternative pathway C3 convertase (C3bBb). It is inactive against factor B, classical/lectin pathway activation, and a broad panel of off-target receptors, ion channels, kinases, and proteases. |
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| ln Vitro |
Compound 6, also known as factor D inhibitor 6, efficiently inhibits the formation of membrane-attack complex (MAC) in lepirudin-anticoagulated 50% human whole blood (IC50 = 0.14 μM) and alternative pathway (AP)-mediated hemolysis in 10% human serum (IC50 = 6 nM)[1]. Compound 6, or factor D inhibitor 6, exhibits moderate inhibition of murine FD (IC50 = 0.86 μM)[1]. With an IC50 value of 70 nM, factor D inhibitor 6 (compound 6) inhibits the AP amplification loop by inhibiting hemolysis and component 3 (C3) deposition on the surface of red blood cells (RBCs)[1].
In vitro, factor D inhibitor 6 potently inhibits alternative pathway (AP)-mediated hemolysis in 10% human serum with an IC50 of 6 nM and inhibits AP-induced membrane attack complex (MAC) formation in lepirudin-anticoagulated 50% human whole blood with an IC50 of 0.14 uM. It also inhibits hemolysis and C3 deposition on red blood cells with an IC50 of 70 nM, consistent with AP amplification loop blockade. It shows modest mouse FD inhibition (IC50 = 0.86 uM). |
| ln Vivo |
Complement activation is dose-dependently inhibited by factor D inhibitor 6 (Compound 6; 1–10 mg/kg; Oral gavage; once; C57Bl/6 mice), reaching maximal inhibition at 10 mg/kg. With an EC50 of 0.034 μM, factor D inhibitor 6 exhibits continuous suppression of LPS-induced AP activation for at least 8 hours after dosage[1].
In vivo, factor D inhibitor 6 (compound 6; 1-10 mg/kg; oral gavage; once; C57Bl/6 mice) dose-dependently inhibits complement activation with full inhibition observed at 10 mg/kg. It shows sustained inhibition of LPS-induced alternative pathway activation for at least 8 hours post-dose with an EC50 of 0.034 uM. This demonstrates its potential for oral administration in complement-mediated disease models. |
| Enzyme Assay |
A biochemical factor D enzyme activity assay is used to assess inhibition: purified human factor D is incubated with a fluorogenic substrate (e.g., Z-Lys-SBzl) and complement factor B in the presence of serially diluted factor D inhibitor 6 (0.1-1000 nM). The generation of cleavage products is monitored by fluorescence, and the IC50 is calculated. Binding affinity (Kd = 6 nM) is determined by surface plasmon resonance (SPR).
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| Cell Assay |
For in vitro hemolysis assays, human red blood cells (RBCs) from healthy donors are treated with an antibody to activate the alternative pathway or rabbit erythrocytes are used. RBCs are incubated with human complement serum in the presence of serially diluted factor D inhibitor 6 (0.1-1000 nM) for 30-60 min at 37degC. Hemoglobin release in the supernatant is measured spectrophotometrically at 415 nm, and the IC50 for AP-mediated hemolysis is calculated. C3 deposition on RBCs is measured by flow cytometry.
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| Animal Protocol |
Animal/Disease Models: C57Bl/6 mice induced by lipopolysaccharide (LPS)[1]
Doses: 1 mg/kg, 3 mg/kg , 10 mg/kg Route of Administration: Oral gavage; once Experimental Results: Dosed-ependently inhibited complement activation, with full inhibition at 10 mg/kg. The in vivo efficacy is evaluated in a mouse model of LPS-induced alternative pathway activation. C57Bl/6 mice are injected intraperitoneally with LPS (e.g., 5 mg/kg) to induce systemic inflammation. Factor D inhibitor 6 is administered orally at doses of 1, 3, and 10 mg/kg, 1 hour before LPS challenge. Blood is collected at 0.5, 1, 2, 4, 6, 8, 12, and 24 hours post-dose. Complement AP activation is assessed by measuring Bb and C5a levels in plasma by ELISA. The EC50 (0.034 uM) and duration of inhibition (>8 h) are determined. |
| ADME/Pharmacokinetics |
Factor D inhibitor 6 has a molecular weight of 484.9 g/mol and a formula of C23H22ClFN6O3. It is orally active with good bioavailability. DMSO solubility is 250 mg/mL (515.56 mM). Detailed in vivo PK parameters (e.g., half-life, Cmax, oral bioavailability) are available in the literature (Nat Chem Biol. 2016 Dec;12(12):1105-1110). The compound shows acceptable plasma exposure and a half-life supporting once-daily oral dosing in rodents.
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| Toxicity/Toxicokinetics |
Detailed toxicological data for factor D inhibitor 6 are not fully published. In preclinical studies, the compound was generally well-tolerated at efficacious doses (≤10 mg/kg). As a selective alternative pathway inhibitor, potential toxicities include increased susceptibility to infections, particularly encapsulated bacteria, due to impaired complement-mediated opsonization. No significant acute organ toxicity has been reported.
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| References | |
| Additional Infomation |
Factor D inhibitor 6 is a research-grade compound not approved for clinical use. It was first described in the literature (Nat Chem Biol. 2016 Dec;12(12):1105-1110). It is a potent, selective, and orally active factor D inhibitor used as a research tool to study the role of the alternative complement pathway in PNH, AMD, IgAN, and other complement-mediated diseases. This product is for laboratory research only.
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| Molecular Formula |
C23H22CLFN6O3
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|---|---|
| Molecular Weight |
484.910586833954
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| Exact Mass |
484.142
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| CAS # |
1386455-51-1
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| PubChem CID |
68283608
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| Appearance |
White to off-white solid powder
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| LogP |
1.9
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
34
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| Complexity |
835
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| Defined Atom Stereocenter Count |
4
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| SMILES |
ClC1=CC=CC(=C1F)[C@@H](C)NC([C@@H]1C[C@H]2C[C@H]2N1C(CN1C2C=NC=CC=2C(C(N)=O)=N1)=O)=O
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| InChi Key |
YAALCKJNOOFODD-SKNMWMDOSA-N
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| InChi Code |
InChI=1S/C23H22ClFN6O3/c1-11(13-3-2-4-15(24)20(13)25)28-23(34)17-8-12-7-16(12)31(17)19(32)10-30-18-9-27-6-5-14(18)21(29-30)22(26)33/h2-6,9,11-12,16-17H,7-8,10H2,1H3,(H2,26,33)(H,28,34)/t11-,12-,16-,17+/m1/s1
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| Chemical Name |
1-[2-[(1R,3S,5R)-3-[[(1R)-1-(3-chloro-2-fluorophenyl)ethyl]carbamoyl]-2-azabicyclo[3.1.0]hexan-2-yl]-2-oxoethyl]pyrazolo[3,4-c]pyridine-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 |
| 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: 250 mg/mL (515.56 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (4.29 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 20.8 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: ≥ 2.08 mg/mL (4.29 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 20.8 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: ≥ 2.08 mg/mL (4.29 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 | 2.0622 mL | 10.3112 mL | 20.6224 mL | |
| 5 mM | 0.4124 mL | 2.0622 mL | 4.1245 mL | |
| 10 mM | 0.2062 mL | 1.0311 mL | 2.0622 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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