Iptacopan CAS 1644670-37-0

Introduction：Basic information about Iptacopan CAS 1644670-37-0, including its chemical name, molecular formula, synonyms, physicochemical properties, and safety information, etc.

Iptacopan Basic information

• Product Name: Iptacopan
• Synonyms: 4-((2S,4S)-4-ethoxy-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoicacid;EOS-62416;LNP023;Benzoic acid, 4-[(2S,4S)-4-ethoxy-1-[(5-methoxy-7-methyl-1H-indol-4-yl)methyl]-2-piperidinyl]-;LNP023(LNP-023;LNP0233;Iptacopan, 10 mM in DMSO;4-((2S,4S)-4-Ethoxy-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid , Iptacopan
• CAS: 1644670-37-0
• MF: C25H30N2O4
• MW: 422.52
• EINECS: 202-303-5
• Mol File: 1644670-37-0.mol

Iptacopan Chemical Properties

• Boiling point: 599.1±50.0 °C(Predicted)
• density: 1.25±0.1 g/cm3(Predicted)
• storage temp.: Store at -20°C
• solubility: DMSO:50.0(Max Conc. mg/mL);118.34(Max Conc. mM)
• pka: 4.07±0.10(Predicted)
• form: Solid
• color: Off-white to gray
• InChIKey: RENRQMCACQEWFC-UGKGYDQZSA-N
• SMILES: C(O)(=O)C1=CC=C([C@@H]2C[C@@H](OCC)CCN2CC2=C(OC)C=C(C)C3=C2C=CN3)C=C1

Iptacopan Usage And Synthesis

Uses

Iptacopan (LNP023) is a first-in-class, orally bioavailable, highly potent and highly selective factor B inhibitor with an IC50 value of 10 nM. Iptacopan shows direct, reversible, and high-affinity binding to human factor B with a KD of 7.9 nM. Iptacopan targets the underlying cause of complement 3 glomerulopathy (C3G)[1][2].

Biological Activity

Iptacopan (LNP023) is a first-in-class, potent, and orally active and highly selective factor B inhibitor with IC50 of 10 nM. Iptacopan binds factor B directly and reversibly with high affinity with a KD of 7.9 nM. Iptacopan targets the underlying cause of C3 glomerulopathy.

in vitro

Iptacopan (LNP023) demonstrates potent inhibition of alternative complement pathway (AP)-induced membrane attack complex (MAC) formation in 50% human serum (IC ₅₀ value of 130 nM).
It exhibits excellent selectivity over other proteases affording IC ₅₀ values of >30 μM across a panel of 41 human proteases, including the AP protein factor D (>100 μM) .

in vivo

Iptacopan (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. < br/> It exhibits moderate half-lives (T _1/2 ; Wistar Han rats 3.4 h, beagle dogs 5.5 h) and C _max (Wistar Han rats 410 nM, beagle dogs 2200 nM) following oral administration (rat 30 and, dog 10 mg/kg).
Iptacopan exhibits terminal elimination half-lives (T _1/2 ; 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 respectively) ).

• Animal Model: C57BL/6 mice with KRN-induced arthritis
• Dosage: 20, 60, and 180 mg/kg
• Administration: Orally gavaged; twice a day (bid) for 14 days
• Result: Blocked KRN-induced arthritis.

target

KD: 7.9 nM (factor B)
IC50: 10 nM (factor B)

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