| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
|
||
| 5mg |
|
||
| 10mg |
|
||
| Other Sizes |
|
Iptacopan (LNP023; LNP-023; Fabhalta) is a highly potent, selective and orally bioavailable factor B (FB) inhibitor (IC50 = 10 nM) with the potential to be used for the treatment of complement-mediated diseases. LNP023 shows direct, reversible, and high-affinity binding to human FB (KD=7.9 nM). 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. Iptacopan (Fabhalta) was approved in 2023 by FDA for treating Paroxysmal nocturnal haemoglobinuria.
| Targets |
KD: 7.9 nM (factor B)[2] IC50: 10 nM (factor B)[2]
|
|---|---|
| ln Vitro |
In 50% of human serum, iptacopan (LNP023) efficiently prevents the formation of membrane attack complexes (MAC) caused by the alternative complement pathway (AP) (IC50 value: 130 nM) [2]. Among 41 human proteases, iptacopan (LNP023) has IC50 values >30 μM, demonstrating excellent selectivity over other proteases, including AP protein factor D (>100 μM) [3].
|
| ln Vivo |
In an experimental model of rat membranous nephropathy, diptacopan (LNP023; 20-180 mg/kg; oral) is effective at both preventive and therapeutic doses and prevents arthritis induced by KRN (150 μL) in mice [2]. ?LNP023 shows a moderate half-life (T1/2; Wistar Han rat 3.4 hours, beagle 5.5 hours) and Cmax (Wistar Han rat 5.5 hours) 410 nM, Beagle 2200 nM) after oral administration (dog 10 mg/kg, rat 30 mg/kg) [3]. ?Iptacopan is caused by large distribution volume (2.3 and 0.6 L/kg) and high plasma clearance (8 and 2 mL/min/kg, respectively) following intravenous administration (1.0 mg/kg in dogs and 0.1 mg/kg in rats) [3].
|
| Enzyme Assay |
In Vitro Inhibition Assays [2].
Compounds were tested for FB inhibition either by using CVF:Bb as stable surrogate of the C3 convertase and purified endogenous C3 as substrate or by using a competition binding assay with FB and a Cy5-labeled small-molecule inhibitor as probe. AP inhibition was measured in 50% human serum or 50% human whole blood by following zymosan A-induced MAC formation. Serum or whole blood was preincubated with compound for 30 min before transfer to zymosan A-coated plates. MAC formation was detected with an anti-C9 neoepitope antibody by ELISA. AP complement deposition in mouse serum was measured in an analogous way except that C3b deposition was detected instead of MAC formation. Further details on protein purification and all in vitro assays are given in SI Appendix. |
| Animal Protocol |
Animal/Disease Models: C57BL/6 mice with KRN-induced arthritis [2]
Doses: 20, 60 and 180 mg/kg: po (oral gavage); twice (two times) daily (bid) for 14 days Experimental Results: Blocks KRN-induced arthritis 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 |
C₂₅H₃₀N₂O₄
|
|---|---|
| Molecular Weight |
422.516706943512
|
| Exact Mass |
422.22
|
| Elemental Analysis |
C, 71.07; H, 7.16; N, 6.63; O, 15.15
|
| CAS # |
1644670-37-0
|
| Related CAS # |
Iptacopan hydrochloride;1646321-63-2
|
| Appearance |
Off-white to gray solid powder
|
| LogP |
1.8
|
| tPSA |
74.8Ų
|
| SMILES |
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
|
| 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
|
| Chemical Name |
4-((2S,4S)-4-ethoxy-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid
|
| Synonyms |
LNP023 Iptacopan LNP-023 LNP 023; Fabhalta
|
| HS Tariff Code |
2934.99.9001
|
| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
|
| Solubility (In Vitro) |
DMSO : ~50 mg/mL (~118.34 mM)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 5 mg/mL (11.83 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 50.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 5 mg/mL (11.83 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 50.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 5 mg/mL (11.83 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.3668 mL | 11.8338 mL | 23.6675 mL | |
| 5 mM | 0.4734 mL | 2.3668 mL | 4.7335 mL | |
| 10 mM | 0.2367 mL | 1.1834 mL | 2.3668 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
