Pelecopan (BCX9930) is a potent, selective and orally bioactive inhibitor of complement factor D. The IC50 is 14.3 nM. Pelecopan targets complement factor D to prevent intravascular and extravascular hemolysis in PNH and may also be used in other alternative pathway-mediated diseases.

Physicochemical Properties

Molecular Formula	C23H19FN2O4
Molecular Weight	406.406369447708
Exact Mass	406.132
CAS #	2378380-49-3
PubChem CID	139560984
Appearance	Off-white to light yellow solid powder
LogP	0.5
Hydrogen Bond Donor Count	2
Hydrogen Bond Acceptor Count	7
Rotatable Bond Count	7
Heavy Atom Count	30
Complexity	579
Defined Atom Stereocenter Count	0
SMILES	C1(CC(O)=O)=CC=CC=C1OCC1=CC(C2C=CN=C(CN)C=2F)=C2OC=CC2=C1
InChi Key	AUARNXJEAZFQCQ-UHFFFAOYSA-N
InChi Code	InChI=1S/C23H19FN2O4/c24-22-17(5-7-26-19(22)12-25)18-10-14(9-16-6-8-29-23(16)18)13-30-20-4-2-1-3-15(20)11-21(27)28/h1-10H,11-13,25H2,(H,27,28)
Chemical Name	2-[2-[[7-[2-(aminomethyl)-3-fluoropyridin-4-yl]-1-benzofuran-5-yl]methoxy]phenyl]acetic acid
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

ln Vitro	Pelecopan inhibits human factor D's proteolytic activity against C3b-bound factor B with an IC50 of 28.1 nM and possesses strong and highly selective inhibitory effect against pure human factor D (IC50 of 14.3 nM) [1]. Pelecopan prevents the buildup of C3 fragments on PNH erythrocytes and totally prevents hemolysis of PNH cells in vitro (IC50 value in rabbit erythrocytes is 29.5 nM) [1].
References	[1]. International Nonproprietary Names for Pharmaceutical Substances (INN). [2]. BCX9930, a Potent, Selective, Oral Factor D Inhibitor, Demonstrates Proof-of-Concept As Monotherapy in Patients with Paroxysmal Nocturnal Hemoglobinuria (PNH). Blood (2020) Volume 136, Supplement 1, 5 November 2. [3]. Preclinical Characterization of BCX9930, a Potent Oral Complement Factor D Inhibitor, Targeting Alternative Pathway-Mediated Diseases Including Paroxysmal Nocturnal Hemoglobinuria (PNH). Blood (2020) Volume 136, Supplement 1, 5 Nove.
Additional Infomation	Pelecopan is an orally bioavailable inhibitor of complement factor D (FD; CFD), a serine protease that cleaves complement factor B, with potential complement system inhibiting activity. Upon oral administration, pelecopan targets, binds to and blocks the activity of FD, thereby inhibiting the cleavage of complement factor B into Ba and Bb in the alternative pathway of the complement cascade. This inhibits FD-mediated signaling and the activation of the alternative complement pathway (ACP), blocks complement-mediated hemolysis in paroxysmal nocturnal hemoglobinuria (PNH) and prevents ACP-induced tissue damage. FD plays a key role in the activation of the ACP.

Solubility Data

Solubility (In Vitro)

DMSO : ~100 mg/mL (~246.06 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.5 mg/mL (6.15 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 25.0 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: ≥ 2.5 mg/mL (6.15 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 25.0 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. Solubility in Formulation 3: ≥ 2.5 mg/mL (6.15 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 25.0 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	2.4606 mL	12.3028 mL	24.6057 mL
	5 mM	0.4921 mL	2.4606 mL	4.9211 mL
	10 mM	0.2461 mL	1.2303 mL	2.4606 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.