| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
|
||
| 10mg |
|
||
| 25mg |
|
||
| 50mg |
|
||
| 100mg |
|
||
| 250mg |
|
||
| 500mg |
|
||
| Other Sizes |
|
Lanifibranor (formerly named as IVA-337) is a novel, potent and well balanced agonist of the pan-peroxisome proliferator-activated receptors (PPAR) with excellent safety profiles and with EC50s of 1.5, 0.87 and 0.21 μM for human PPARα, PPARσ and PPARγ, respectively. In models relevant to the pathophysiology of non-alcoholic steato hepatitis (NASH), lanifibranor showed significant activity, indicating potential therapeutic benefit for NASH patients. In the mouse model of liver fibrosis induced by CCl4, lanifibranor showed a strong anti-fibrotic effect in addition to its excellent anti-hyperglycemic and hypolipidemic efficacy in the db/db mouse model. Since lanifibranor did not affect rats' hematocrit, plasma volume, or heart weight in contrast to other PPARγ agonists, it may one day be developed as a therapeutic for the treatment of nonalcoholic steatohepatitis (NASH).
| Targets |
PPARγ (EC50 = 206 nM); PPARδ (IC50 = 866 nM); PPARα (IC50 = 1537 nM)
|
|
|---|---|---|
| ln Vitro |
|
|
| ln Vivo |
|
|
| Enzyme Assay |
PPAR Transactivation Assays
These cell-based assays were carried out using Cos-7 cells transfected with a chimeric human or murine PPARα-Gal4 receptor expression plasmid (or PPARδ-Gal4, or PPARγ-Gal4) and a 5Gal4 pGL3 TK Luc reporter plasmid. Transfections were performed by a chemical agent (Jet PEI). Transfected cells were distributed in 384-well plates and were allowed to recover for 24 h. The culture medium was then removed and replaced by fresh medium containing the compounds to be tested (variable concentration in 0.5% DMSO). After an overnight incubation, luciferase expression was measured by adding SteadyGlo according to the manufacturer’s instructions (Promega). Fenofibric acid at 10–5 M (PPARα), GW501516 at 10–8 M (PPARδ), and rosiglitazone at 10–6 M (PPARγ) were used as references. Results were expressed as fold induction compared to basal level or as percentage activity compared to references taken as 100%. Calculation and plate validation from run to run were done using the software Assay Explorer (MDL). Serial dilutions of compounds (final concentration ranging from 30 to 0.001 μM) were tested in triplicate on an automated screening core-system from Beckman or Caliper. The EC50 calculation was done using Assay Explorer (MDL) and was determined simultaneously on human and mouse PPARα/δ/γ[1]. |
|
| Cell Assay |
For seven days, dimethyl sulfoxide 0.1% or a compound (IVA337, 3 µM; rosiglitazone, 3 µM; fenofibrate, 30 µM; or GW501516, 3 µM) were added to plastic six-well plates to seed human primary HSCs. α-smooth muscle actin (α-SMA) expression was used to measure hHSC activation using western blot.
|
|
| Animal Protocol |
|
|
| References |
|
| Molecular Formula |
C19H15CLN2O4S2
|
|
|---|---|---|
| Molecular Weight |
434.0162
|
|
| Exact Mass |
434.02
|
|
| Elemental Analysis |
C, 52.47; H, 3.48; Cl, 8.15; N, 6.44; O, 14.71; S, 14.74
|
|
| CAS # |
927961-18-0
|
|
| Related CAS # |
|
|
| Appearance |
White to light brown solid powder
|
|
| LogP |
4.5
|
|
| tPSA |
434.016177
|
|
| SMILES |
C1=CC2=C(C=C1S(=O)(=O)N3C4=C(C=C(C=C4)Cl)C=C3CCCC(=O)O)SC=N2
|
|
| InChi Key |
OQDQIFQRNZIEEJ-UHFFFAOYSA-N
|
|
| InChi Code |
InChI=1S/C19H15ClN2O4S2/c20-13-4-7-17-12(8-13)9-14(2-1-3-19(23)24)22(17)28(25,26)15-5-6-16-18(10-15)27-11-21-16/h4-11H,1-3H2,(H,23,24)
|
|
| Chemical Name |
4-[1-(1,3-benzothiazol-6-ylsulfonyl)-5-chloroindol-2-yl]butanoic acid
|
|
| Synonyms |
|
|
| 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) |
|
|||
|---|---|---|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.75 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 25.0 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: 2.08 mg/mL (4.78 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 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: ≥ 2.08 mg/mL (4.78 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 | 2.3040 mL | 11.5202 mL | 23.0404 mL | |
| 5 mM | 0.4608 mL | 2.3040 mL | 4.6081 mL | |
| 10 mM | 0.2304 mL | 1.1520 mL | 2.3040 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.
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT06126562 | Active Recruiting |
Drug: Lanifibranor | Pharmacokinetic | Chia Tai Tianqing Pharmaceutical Group Co., Ltd. |
October 31, 2023 | Phase 1 |
| NCT04849728 | Recruiting | Drug: IVA337 Drug: Placebo |
NASH - Nonalcoholic Steatohepatitis | Inventiva Pharma | August 19, 2021 | Phase 3 |
| NCT05232071 | Recruiting | Drug: IVA337 Drug: Placebo |
NASH - Nonalcoholic Steatohepatitis Diabetes Mellitus, Type 2 |
Inventiva Pharma | June 29, 2022 | Phase 2 |
| NCT03459079 | Recruiting | Drug: Lanifibranor Other: Placebo |
Nonalcoholic Fatty Liver Disease (NAFLD) Type 2 Diabetes (T2DM) |
University of Florida | August 14, 2018 | Phase 2 |
| NCT03866369 | Completed | Drug: Lanifibranor Drug: Placebo |
Healthy Subjects | Inventiva Pharma | January 17, 2019 | Phase 1 |
Abstract ImageJ Med Chem.2018 Mar 22;61(6):2246-2265.
Effect of IVA337 on formation of stress fibres and transforming growth factor (TGF)-β signalling in primary human fibroblasts.Ann Rheum Dis.2016Dec;75(12):2175-2183. |
|---|
Increased expression of peroxisome proliferator-activated receptor (PPAR)α and PPARγ in human systemic sclerosis (SSc) skin.Ann Rheum Dis.2016Dec;75(12):2175-2183. |
IVA337 attenuates dermal thickness, collagen content and myofibroblast accumulation in preventative model of fibrosis.Ann Rheum Dis.2016Dec;75(12):2175-2183. |
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
