LNP023 hydrochloride

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

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].

Name	LNP023 hydrochloride

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	Signaling Pathways >> Immunology/Inflammation >> Complement System Research Areas >> Inflammation/Immunology Research Areas >> Metabolic Disease
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.

Molecular Formula	C₂₅H₃₁ClN₂O₄
Molecular Weight	458.98

LNP023 hydrochloride

Use of LNP023 hydrochloride

Names

LNP023 hydrochloride Biological Activity

Chemical & Physical Properties