| Identification | Back Directory | [Name]
4-((2S,4S)-4-ethoxy-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoicacidhydrochloride | [CAS]
1646321-63-2 | [Synonyms]
EOS-61917
LNP023 hcl
Iptacopan HCl
Iptacopan(lnp023)
LNP023 hydrochloride
Iptacopanhydrochloride
Iptacopan (LNP023) hydrochloride
Iptacopanhydrochloride，LNP023 hcl
4-((2S,4S)-4-ethoxy-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoicacidhydrochloride | [Molecular Formula]
C25H31ClN2O4 | [MDL Number]
MFCD32701924 | [MOL File]
1646321-63-2.mol | [Molecular Weight]
458.978 |
| Chemical Properties | Back Directory | [storage temp. ]
Store at -20°C | [solubility ]
DMSO : 250 mg/mL (544.69 mM; Need ultrasonic)| | [form ]
A solid | [color ]
White to off-white | [Water Solubility ]
Water : 50 mg/mL (108.94 mM; ultrasonic and warming and heat to 60°C) | [InChIKey]
SEZXOFFLNHXEJE-QHWHZDSMNA-N | [SMILES]
C(N1CC[C@H](OCC)C[C@H]1C1C=CC(C(=O)O)=CC=1)C1C(=CC(C)=C2NC=CC=12)OC.Cl |&1:4,9,r| |
| Hazard Information | Back Directory | [Uses]
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]. | [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. DOI:10.1053/j.seminhematol.2018.02.002
[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. DOI:10.1073/pnas.1820892116
[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. DOI:10.1021/acs.jmedchem.9b01870 |
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