NXT629 (NXT-629) is a novel, potent, selective and competitive hPPAR-α antagonist (IC50 =77 nM) that may be beneficial in diseases such as ovarian cancer and melanoma where PPARα and fatty acid oxidation are involved. Peroxisome-proliferator activated receptors (PPAR) are members of the nuclear hormone receptor superfamily which regulate gene transcription. PPARα is a key regulator of lipid homeostasis and a negative regulator of inflammation. PPARα expression is upregulated in diseased tissues such as melanoma, chronic lymphocytic leukemia, ovarian and prostate cancer.
Physicochemical Properties
| Molecular Formula | C35H39N5O3S |
| Molecular Weight | 609.780866861343 |
| Exact Mass | 609.277 |
| CAS # | 1454925-59-7 |
| PubChem CID | 71721539 |
| Appearance | Light yellow to yellow solid powder |
| LogP | 6.5 |
| Hydrogen Bond Donor Count | 1 |
| Hydrogen Bond Acceptor Count | 6 |
| Rotatable Bond Count | 12 |
| Heavy Atom Count | 44 |
| Complexity | 1060 |
| Defined Atom Stereocenter Count | 0 |
| SMILES | S(C1C=CC=CC=1)(NC1=CN=C(C=C1)C1C=CC(=CC=1)CCCC1=NN(C(N1CC)=O)CC1C=CC(=CC=1)C(C)(C)C)(=O)=O |
| InChi Key | IRSFLNXJVJKMDT-UHFFFAOYSA-N |
| InChi Code | InChI=1S/C35H39N5O3S/c1-5-39-33(37-40(34(39)41)25-27-16-20-29(21-17-27)35(2,3)4)13-9-10-26-14-18-28(19-15-26)32-23-22-30(24-36-32)38-44(42,43)31-11-7-6-8-12-31/h6-8,11-12,14-24,38H,5,9-10,13,25H2,1-4H3 |
| Chemical Name | N-[6-[4-[3-[1-[(4-tert-butylphenyl)methyl]-4-ethyl-5-oxo-1,2,4-triazol-3-yl]propyl]phenyl]pyridin-3-yl]benzenesulfonamide |
| 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) |
Biological Activity
| ln Vitro | NXT629 (Compound 33) is a strong and selective PPAR-α antagonist with an IC50 of 77 nM for human PPARα and an IC50 between 6.0 and 15 for other nuclear hormone receptors such as PPARδ, PPARγ, Erβ, GR and TRβ, respectively. NXT629 also suppresses PPARα, PPARβ/δ and PPARγ with IC50 of 2.3, 35.1 and 6.9 μM respectively[2]. |
| ln Vivo | Compound 33, also known as NXT629, had favorable pharmacokinetics in mice and notably decreased the expression of the PPARα target gene Fgf21, or fibroblast growth factor 21, in mice that had been starved [1]. NXT629 (30 mg/kg, intraperitoneally injected once daily for 6 weeks) suppresses the growth of C57Bl/6 mice and delays the growth of subcutaneous SKOV-3 tumors in nude mice. On FGF-induced angiogenesis, NXT629 (30 mg/kg, ip) has negligible anti-angiogenic effects. B16F10 melanoma cells' experimental growth and metastasis to mice lungs is inhibited by NXT629 (3, 30 mg/kg, ip) [2]. |
| References |
[1]. Identification of the first potent, selective and bioavailable PPARα antagonist. Bioorg Med Chem Lett. 2014 May 15;24(10):2267-72. [2]. In vitro and in vivo pharmacology of NXT629, a novel and selective PPARα antagonist. Eur J Pharmacol. 2017 Aug 15;809:130-140. |
Solubility Data
| Solubility (In Vitro) | DMSO : ~125 mg/mL (~204.99 mM) |
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (3.41 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 20.8 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 (3.41 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 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. Solubility in Formulation 3: ≥ 2.08 mg/mL (3.41 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.6399 mL | 8.1997 mL | 16.3994 mL | |
| 5 mM | 0.3280 mL | 1.6399 mL | 3.2799 mL | |
| 10 mM | 0.1640 mL | 0.8200 mL | 1.6399 mL |