Factor D inhibitor 6 is a specific, orally bioactive factor D (factor D) inhibitor (antagonist) with IC50 of 30 nM and a Kd of 6 nM. Factor D inhibitor 6 is inactive against factor B, kinin and lectin complement pathway activation as well as a broad range of receptors, ion channels, kinases and proteases.

Physicochemical Properties

Molecular Formula	C23H22CLFN6O3
Molecular Weight	484.910586833954
Exact Mass	484.142
CAS #	1386455-51-1
PubChem CID	68283608
Appearance	White to off-white solid powder
LogP	1.9
Hydrogen Bond Donor Count	2
Hydrogen Bond Acceptor Count	6
Rotatable Bond Count	6
Heavy Atom Count	34
Complexity	835
Defined Atom Stereocenter Count	4
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
InChi Key	YAALCKJNOOFODD-SKNMWMDOSA-N
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
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
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)

Biological Activity

Targets	IC50: 30 nM (Factor D)[1] Kd: 6 nM (Factor D)[1]
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].
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].
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.
References	[1]. Small-molecule Factor D Inhibitors Targeting the Alternative Complement Pathway. Nat Chem Biol. 2016 Dec;12(12):1105-1110.

Solubility Data

Solubility (In Vitro)

DMSO: 250 mg/mL (515.56 mM)

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. 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. 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 corn oil and mix evenly.  (Please use freshly prepared in vivo formulations for optimal results.)

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.