Iptacopan free base
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MedKoo CAT#: 558964

CAS#: 1644670-37-0 (free base)

Description: Iptacopan, also known as LNP023, is a complement Factor B Inhibitor (IC50=10 nM). LNP023 improves LN in MRL/lpr mice. The mechanism is as follows: LNP023 binds to CFB to inhibit the activation of the alternative complement pathway. LNP023 treatment for LN may also play a role in regulating the protein expression of AKT, TNF-α, and STST3. LNP023 showed low clearance and high bioavailability (62.2%). Furthermore, four minor metabolites from rat plasma were detected and identified by LC combined with high-resolution mass spectrometry. The metabolic pathways were O-deethylation (M1), hydroxylation (M4), oxidation (M3), and acyl-glucuronidation (M2).

Chemical Structure

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Iptacopan free base
CAS# 1644670-37-0 (free base)
Product data Instruction

Theoretical Analysis

MedKoo Cat#: 558964
Name: Iptacopan free base
CAS#: 1644670-37-0 (free base)
Chemical Formula: C25H30N2O4
Exact Mass: 422.22
Molecular Weight: 422.520
Elemental Analysis: C, 71.07; H, 7.16; N, 6.63; O, 15.15

Price and Availability

Size Price Availability Quantity
5mg USD 150 Ready to Ship
10mg USD 250 Ready to Ship
25mg USD 450 Ready to Ship
50mg USD 750 Ready to Ship
100mg USD 1250 Ready to Ship
200mg USD 1950 Ready to Ship
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Related CAS #: 1646321-63-2 (HCl)   1644670-37-0 (free base)   1644670-38-1 (TFA)    

Synonym: LNP-023; LNP 023; LNP023; Iptacopan;

IUPAC/Chemical Name: 4-((2S,4S)-4-ethoxy-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid

InChi Key: RENRQMCACQEWFC-UGKGYDQZSA-N

InChi Code: InChI=1S/C25H30N2O4/c1-4-31-19-10-12-27(22(14-19)17-5-7-18(8-6-17)25(28)29)15-21-20-9-11-26-24(20)16(2)13-23(21)30-3/h5-9,11,13,19,22,26H,4,10,12,14-15H2,1-3H3,(H,28,29)/t19-,22-/m0/s1

SMILES Code: O=C(O)C1=CC=C([C@H]2N(CC3=C(OC)C=C(C)C4=C3C=CN4)CC[C@H](OCC)C2)C=C1

Appearance: Solid powder

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

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility: Soluble in DMSO

Shelf Life: >3 years if stored properly

Drug Formulation: This drug may be formulated in DMSO

Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code: 2934.99.9001

More Info: Lupus nephritis (LN) is the most common complication of systemic lupus erythematosus (SLE), and the abnormal activation of the alternative complement pathway is associated with the pathogenesis of LN. As an inhibitor of complement factor B (CFB) in the alternative pathway, LNP023 has been used in the treatment of a variety of renal diseases with abnormal complement system involvement, such as paroxysmal nocturnal hemoglobinuria, IgA nephropathy, and membranous nephropathy.

Biological target: 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).
In vitro activity: TBD
In vivo activity: After the 19th and 20th weeks of LNP023 interventional therapy, the urinary protein concentration in MRL/lpr mice in the LNP023 group was significantly lower than that in mice in the MRL/lpr model group and showed a decreasing trend, indicating that LNP023 alleviated lupus kidney injury in MRL/lpr mice (Fig. 2B). Reference: Biomed Pharmacother. 2022 Sep;153:113433. https://pubmed.ncbi.nlm.nih.gov/36076550/

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMSO 50.0 118.34

Preparing Stock Solutions

The following data is based on the product molecular weight 422.52 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Recalculate based on batch purity %
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 1.15 mL 5.76 mL 11.51 mL
5 mM 0.23 mL 1.15 mL 2.3 mL
10 mM 0.12 mL 0.58 mL 1.15 mL
50 mM 0.02 mL 0.12 mL 0.23 mL
Formulation protocol: 1. Chen K, Deng Y, Shang S, Tang L, Li Q, Bai X, Chen X. Complement factor B inhibitor LNP023 improves lupus nephritis in MRL/lpr mice. Biomed Pharmacother. 2022 Sep;153:113433. doi: 10.1016/j.biopha.2022.113433. Epub 2022 Jul 26. PMID: 36076550.
In vitro protocol: TBD
In vivo protocol: 1. Chen K, Deng Y, Shang S, Tang L, Li Q, Bai X, Chen X. Complement factor B inhibitor LNP023 improves lupus nephritis in MRL/lpr mice. Biomed Pharmacother. 2022 Sep;153:113433. doi: 10.1016/j.biopha.2022.113433. Epub 2022 Jul 26. PMID: 36076550.

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1: Bomback AS, Kavanagh D, Vivarelli M, Meier M, Wang Y, Webb NJA, Trapani AJ, Smith RJH. Alternative Complement Pathway Inhibition With Iptacopan for the Treatment of C3 Glomerulopathy-Study Design of the APPEAR-C3G Trial. Kidney Int Rep. 2022 Aug 2;7(10):2150-2159. doi: 10.1016/j.ekir.2022.07.004. PMID: 36217526; PMCID: PMC9546729.


2: Chen K, Deng Y, Shang S, Tang L, Li Q, Bai X, Chen X. Complement factor B inhibitor LNP023 improves lupus nephritis in MRL/lpr mice. Biomed Pharmacother. 2022 Sep;153:113433. doi: 10.1016/j.biopha.2022.113433. Epub 2022 Jul 26. PMID: 36076550.


3: Jang JH, Wong L, Ko BS, Yoon SS, Li K, Baltcheva I, Nidamarthy PK, Chawla R, Junge G, Yap ES. Iptacopan monotherapy in patients with paroxysmal nocturnal hemoglobinuria: a 2-cohort open-label proof-of-concept study. Blood Adv. 2022 Aug 9;6(15):4450-4460. doi: 10.1182/bloodadvances.2022006960. PMID: 35561315; PMCID: PMC9636331.


4: Jiang X, Pan R. Pharmacokinetics and metabolism of LNP023 in rats by liquid chromatography combined with electrospray ionization-tandem mass spectrometry. Biomed Chromatogr. 2021 Mar;35(3):e5006. doi: 10.1002/bmc.5006. Epub 2020 Nov 11. PMID: 33067853.


5: Mainolfi N, Ehara T, Karki RG, Anderson K, Mac Sweeney A, Liao SM, Argikar UA, Jendza K, Zhang C, Powers J, Klosowski DW, Crowley M, Kawanami T, Ding J, April M, Forster C, Serrano-Wu M, Capparelli M, Ramqaj R, Solovay C, Cumin F, Smith TM, Ferrara L, Lee W, Long D, Prentiss M, De Erkenez A, Yang L, Liu F, Sellner H, Sirockin F, Valeur E, Erbel P, Ostermeier D, Ramage P, Gerhartz B, Schubart A, Flohr S, Gradoux N, Feifel R, Vogg B, Wiesmann C, Maibaum J, Eder J, Sedrani R, Harrison RA, Mogi M, Jaffee BD, Adams CM. Discovery of 4-((2S, 4S)-4-Ethoxy-1-((5-methoxy-7-methyl-1H-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. Epub 2020 Feb 19. PMID: 32073845.


6: Mastellos DC, Reis ES, Yancopoulou D, Risitano AM, Lambris JD. 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. Epub 2018 Feb 14. PMID: 30032754; PMCID: PMC6060635.