FD-IN-1 (Compound 12) is an orally bioavailable and selective factor D (FD) inhibitor with an IC50 of 12 nM. Complement FD, a highly specific S1 serine protease, plays a central role in the alternative complement pathway of the innate immune system. FD-IN-1 also inhibits factor XIa (FXIa) and Tryptase β2 with IC50s of 7.7 and 6.5 µM, respectively.

Product information

CAS Number: 1646682-14-5

Molecular Weight: 377.43

Formula: C23H23NO4

Chemical Name: 2-[2-({3'-[(1S)-1-amino-2-hydroxyethyl]-[1,1'-biphenyl]-3-yl}methoxy)phenyl]acetic acid

Smiles: N[C@H](CO)C1C=C(C=CC=1)C1=CC(COC2=CC=CC=C2CC(O)=O)=CC=C1

InChiKey: XHLXBWRISOPXQB-OAQYLSRUSA-N

InChi: InChI=1S/C23H23NO4/c24-21(14-25)19-9-4-8-18(12-19)17-7-3-5-16(11-17)15-28-22-10-2-1-6-20(22)13-23(26)27/h1-12,21,25H,13-15,24H2,(H,26,27)/t21-/m1/s1

Technical Data

Appearance: Solid Power

Purity: ≥98% (or refer to the Certificate of Analysis)

Solubility: DMSO : 62.5 mg/mL (165.59 mM; ultrasonic and warming and heat to 80°C).

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥12 months if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined

HS Tariff Code: 382200

How to use

In Vitro:

FD-IN-1 (Compound 12) exhibits functional inhibition of AP activation (IC50=0.26 μM) in vitro in a membrane attack complex (MAC) deposition assay using 50% human whole blood (WB).

In Vivo:

FD-IN-1 (Compound 12) demonstrates systemic suppression of AP activation in a lipopolysaccharide-induced alternative complement pathway (AP) activation model as well as local ocular suppression in intravitreal injection-induced AP activation model in mice expressing human FD. FD-IN-1 (Compound 12) exhibits high oral bioavailability (C57BL6 mice 83%, Beagle dogs 70%) following oral administration (mice and dogs 10 mg/kg). FD-IN-1 (Compound 12) exhibits terminal elimination half-lives (C57BL6 mice 1.6 h and Beagle dogs 3.8 h) following intravenous administration (mice and dogs 1 mg/kg).

References:

1. Karki RG, et al. Design, Synthesis, and Preclinical Characterization of Selective Factor D Inhibitors Targeting the Alternative Complement Pathway. J Med Chem. 2019 May 9;62(9):4656-4668.

Products are for research use only. Not for human use.