LNP023 hydrochloride

Modify Date: 2024-01-04 18:53:09

LNP023 hydrochloride Structure
LNP023 hydrochloride structure
Common Name LNP023 hydrochloride
CAS Number 1646321-63-2 Molecular Weight 458.98
Density N/A Boiling Point N/A
Molecular Formula C25H31ClN2O4 Melting Point N/A
MSDS N/A Flash Point N/A

 Use of LNP023 hydrochloride


LNP023 hydrochloride is an orally bioavailable, highly potent and highly selective factor B inhibitor. LNP023 shows direct, reversible, and high-affinity binding to human factor B with a KD of 7.9 nM. LNP023 inhibits factor B with an IC50 value of 10 nM[1][2].

 Names

Name LNP023 hydrochloride

 LNP023 hydrochloride Biological Activity

Description LNP023 hydrochloride is an orally bioavailable, highly potent and highly selective factor B inhibitor. LNP023 shows direct, reversible, and high-affinity binding to human factor B with a KD of 7.9 nM. LNP023 inhibits factor B with an IC50 value of 10 nM[1][2].
Related Catalog
Target

KD: 7.9 nM (factor B)[2] IC50: 10 nM (factor B)[2]

In Vitro LNP023 demonstrates potent inhibition of alternative complement pathway (AP)-induced membrane attack complex (MAC) formation in 50% human serum (IC50 value of 130 nM)[2]. LNP023 exhibits excellent selectivity over other proteases affording IC50 values of >30 μM across a panel of 41 human proteases, including the AP protein factor D (>100 μM)[3].
In Vivo LNP023 (20-180 mg/kg; oral administration) prevents KRN (150 μL)-induced arthritis in mice and is effective upon prophylactic and therapeutic dosing in an experimental model of membranous nephropathy in rats[2]. LNP023 exhibits moderate half-lives (T1/2; Wistar Han rats 3.4 h, beagle dogs 5.5 h) and Cmax (Wistar Han rats 410 nM, beagle dogs 2200 nM) following oral administration (rat 30 and, dog 10 mg/kg)[3]. LNP023 exhibits terminal elimination half-lives (T1/2; Wistar Han rats 7 h, beagle dogs 5.6 h) due to high plasma clearance (8, and 2 mL/min/kg respectively combined with large volumes of distribution (2.3, and 0.6 L/kg respectively) following intravenous administration (rat 1.0 and, dog 0.1 mg/kg)[3]. Animal Model: C57BL/6 mice with KRN-induced arthritis[2] Dosage: 20, 60, and 180 mg/kg Administration: Orally gavaged; twice a day (b.i.d.) for 14 days Result: Blocked KRN-induced arthritis.
References

[1]. Dimitrios C Mastellos, et al. Expanding Complement Therapeutics for the Treatment of Paroxysmal Nocturnal Hemoglobinuria. Semin Hematol. 2018 Jul;55(3):167-175.

[2]. Anna Schubart, et al. Small-molecule Factor B Inhibitor for the Treatment of Complement-Mediated Diseases. Proc Natl Acad Sci U S A. 2019 Apr 16;116(16):7926-7931.

[3]. Nello Mainolfi, et al. Discovery of 4-((2 S,4 S)-4-Ethoxy-1-((5-methoxy-7-methyl-1 H-indol-4-yl)methyl)piperidin-2-yl)benzoic Acid (LNP023), a Factor B Inhibitor Specifically Designed To Be Applicable to Treating a Diverse Array of Complement Mediated Diseases. J Med Chem. 2020 Jun 11;63(11):5697-5722.

 Chemical & Physical Properties

Molecular Formula C25H31ClN2O4
Molecular Weight 458.98