CAS Number446859-33-2
Synonyms2-[3-(6-Methyl-2-pyridinyl)-1H-pyrazol-4-yl]-1,5-naphthyridine; 2-[3-(6-Methylpyridin-2-yl)-1H-pyrazol-4-yl]-1,5-naphthyridine; 2-(3-(6-Methylpyridin-2-yl)-1H-pyrazol-4-yl)-1,5-naphthyridine; 2-[5-(6-methylpyridin-2-yl)-1H-pyrazol-4-yl]-1,5-naphthyridine; 1vjy; SJN 2511; RepSox
Molecular FormulaC17H13N5
Molecular Weight287.32
Density1.3±0.1 g/cm3
Boiling Point501.9±50.0 °C at 760 mmHg
Melting Point195 °C
AppearanceSolid;White to Almost white powder to crystal
Symbol
Signal WordWarning
| Chemical & Physical Properties | |
|---|---|
| CAS Number | 446859-33-2 |
| Catalog No. | 2A-9078774 |
| Chinese Name | 2-(3-(6-甲基吡啶-2-基)-1H-吡唑-4-基)-1,5-萘啶 |
| Synonyms | 2-[3-(6-Methyl-2-pyridinyl)-1H-pyrazol-4-yl]-1,5-naphthyridine; 2-[3-(6-Methylpyridin-2-yl)-1H-pyrazol-4-yl]-1,5-naphthyridine; 2-(3-(6-Methylpyridin-2-yl)-1H-pyrazol-4-yl)-1,5-naphthyridine; 2-[5-(6-methylpyridin-2-yl)-1H-pyrazol-4-yl]-1,5-naphthyridine; 1vjy; SJN 2511; RepSox |
| Molecular Formula | C17H13N5 |
| Molecular Weight | 287.32 |
| Density | 1.3±0.1 g/cm3 |
| Boiling Point | 501.9±50.0 °C at 760 mmHg |
| Melting Point | 195 °C |
| Appearance | Solid;White to Almost white powder to crystal |
| Water Solubility | DMSO: >20mg/mL |
| Storage Condition | Store at +4°C |
| Application | RepSox is a potent, selective TGFβR-1/ALK5 inhibitor that inhibits ALK5 autophosphorylation with an IC50 of 4 nM. |
| PubChem ID | 584518 |
| SMILES | Cc1cccc(-c2[nH]ncc2-c2ccc3ncccc3n2)n1 |
| InChI | InChI=1S/C17H13N5/c1-11-4-2-5-16(20-11)17-12(10-19-22-17)13-7-8-14-15(21-13)6-3-9-18-14/h2-10H,1H3,(H,19,22) |
| InChI Key | LBPKYPYHDKKRFS-UHFFFAOYSA-N |
| Hazard Symbols | transportation |
| Bioactivity | RepSox is a potent and selective of the TGFβR-1/ALK5 inhibitor which inhibits ALK5 autophosphorylation with IC50 of 4 nM. Related Catalog Signaling Pathways >> TGF-beta/Smad >> TGF-β Receptor Research Areas >> Cancer Target IC50: 4 nM (ALK5 autophosphorylation)[1] In Vitro RepSox also inhibits ATP binding to ALK5 with IC50 of 23 nM. RepSox shows potent activity in both binding and cellular assays and exhibits selectivity over p38 mitogen-activated protein kinase. with IC50 of >16 μM[1]. RepSox act s as an inhibitor of the Tgfβ1 kinase. Treatment with 25 μM RepSox almost completely eliminates Smad3 phosphorylation, indicating that RepSox strongly inhibits Tgfβ signaling in somatic cells. RepSox is most effective at replacing Sox2 during days 10-11 after transduction and that therefore cultures of Oct4, Klf4, and cMyc-transduced MEFs give rise to intermediates capable of responding to RepSox treatment. These intermediates appear at day 4 post-transduction and peak at days 10-11. Treatment with RepSox decreased the proportion of cells in G2/M phase of the cell cycle, indicating it does not increase the proliferation rate of these partially reprogrammed cells[2]. Kinase Assay The kinase domain of ALK5 is cloned by PCR and expressed in a baculovirus/Sf9 cells system. The protein is 6-His tagged in the C terminus and purified by affinity chromatography using a Ni2+column, and the obtained material is used to assess compound activity in an autophosphorylation assay. Purified enzyme (10 nM) is incubated in 50 μL of Tris buffer (Tris 50 mM, pH 7.4; NaCl, 100 mM; MgCl2, 5 mM; MnCl2, 5 mM; and DTT, 10 mM). The enzyme is preincubated with different concentrations of RepSox (0.1% DMSO final concentration in the test) for 10 min at 37°C. The reaction is then initiated by the addition of 3 μM ATP (0.5 μCi γ-33P-ATP). After 15 min at 37°C, phosphorylation is stopped by the addition of SDS−PAGE sample buffer (50 mM Tris-HCl, pH 6.9, 2.5% glycerol, 1% SDS, and 5% β-mercaptoethanol). The samples are boiled for 5 min at 95°C and run on a 12% SDS−PAGE. Dried gels are exposed to a phosphor screen overnight. ALK5 autophosphorylation is quantified using a Storm imaging system[1]. Cell Assay To test anti-TGF-β activity of compounds, HepG2 cells are seeded in 96 well microplates at a concentration of 35000 cells per well in 200 μL of serum-containing medium. The microplates are then placed for 24 h in a cell incubator at 37°C, 5% CO2 atm. RepSox dissolved in DMSO are then added at concentrations of 50 nM to 10 μM (final concentration of DMSO 1%) for 30 min prior to the addition of recombinant TGF-β (1 ng/mL). After an overnight incubation, the cells are washed with PBS and lysed by addition of 10 μL of passive lysis buffer. Inhibition of luciferase activity relative to control groups is used as a measure of compound activity. A concentration−response curve is constructed from which an IC50 value is determined graphically[1]. References [1]. Gellibert F, et al. Identification of 1,5-naphthyridine derivatives as a novel series of potent and selective TGF-beta type I receptor inhibitors. J Med Chem. 2004 Aug 26;47(18):4494-506. [2]. Ichida JK, et al. A small-molecule inhibitor of tgf-Beta signaling replaces sox2 in reprogramming by inducing nanog. Cell Stem Cell. 2009 Nov 6;5(5):491-503. Chemical & Physical Properties Density 1.3±0.1 g/cm3 Boiling Point 501.9±50.0 °C at 760 mmHg Melting Point 195 °C Molecular Formula C17H13N5 Molecular Weight 287.319 Flash Point 230.5±23.1 °C Exact Mass 287.117096 PSA 67.35000 LogP 1.28 Vapour Pressure 0.0±1.2 mmHg at 25°C Index of Refraction 1.692 InChIKey LBPKYPYHDKKRFS-UHFFFAOYSA-N SMILES Cc1cccc(-c2[nH]ncc2-c2ccc3ncccc3n2)n1 Storage condition Store at +4°C Water Solubility DMSO: >20mg/mL |
| Use of | Properties Name 2-[5-(6-methylpyridin-2-yl)-1H-pyrazol-4-yl]-1,5-naphthyridine Synonym More Synonyms RepSox Biological Activity Related Catalog Signaling Pathways >> TGF-beta/Smad >> TGF-β Receptor Research Areas >> Cancer IC50: 4 nM (ALK5 autophosphorylation)[1] References [1]. Gellibert F, et al. Identification of 1,5-naphthyridine derivatives as a novel series of potent and selective TGF-beta type I receptor inhibitors. J Med Chem. 2004 Aug 26;47(18):4494-506. [2]. Ichida JK, et al. A small-molecule inhibitor of tgf-Beta signaling replaces sox2 in reprogramming by inducing nanog. Cell Stem Cell. 2009 Nov 6;5(5):491-503. Chemical & Physical Properties Molecular Formula C17H13N5 Exact Mass 287.117096 PSA 67.35000 Index of Refraction 1.692 InChIKey LBPKYPYHDKKRFS-UHFFFAOYSA-N |
| Transport Info | Shipping Name: UN |
| MSDS Transport Info | Module 14. Shipping information 14.1 UN dangerous goods number European Dangerous Regulations for land transport: 2811 International Dangerous Regulations for sea transport: 2811 International Dangerous Regulations for air transport: 2811 14.2 United Nations shipping name European Land Transport Dangerous Regulations: TOXIC SOLID, ORGANIC, N.O.S. (RepSox) IMDG: TOXIC SOLID, ORGANIC, N.O.S. (RepSox) International air transport hazard regulations: Toxic solid, organic, n.o.s. (RepSox) 14.3 Transport hazard categories European Land Transport Danger Regulations: 6.1 International Maritime Transport Danger Regulations: 6.1 International Air Transport Danger Regulations: 6.1 14.4 Package group European Land Transport Danger Regulations: III International Maritime Transport Danger Regulations: III International Air Transport Danger Regulations: III 14.5 Environmental hazards European Land Transport Danger Regulations: No International Maritime Danger Regulations International Air Transport Danger Regulations: No Marine pollutants (yes/no): No 14.6 Special reminder to users No data available |
| Related Products in Pharmaceutical Intermediates | ||
|---|---|---|
| (1R,2S,3R,4R)-2,3-Dihydroxy-4-(Hydroxymethyl)-1-aminocyclopentanehydrocloride | 79200-57-0 | 2A-9078608 |
| Bicyclo[2.2.1]heptane-2,3-dimethanol | 45849-05-6 | 2A-9078634 |
| (R)-2-Thienylglycine | 43189-45-3 | 2A-9078668 |
| (1R,5S)-tert-butyl7-benzyl-3,7-diazabicyclo[3.3.1]nonane-3-carboxylate | 327940-71-8 | 2A-9078702 |
| Ethyl5-oxo-1,2,3,5-tetrahydroimidazo[1,2-a]pyridine-8-carboxylate | 439118-88-4 | 2A-9078727 |
| (R)-3,3,3-Trifluoro-2-hydroxy-2-Methylpropionicacid | 44864-47-3 | 2A-9078778 |
| 3-Morpholinyl-propionicacid | 4497-04-5 | 2A-9078782 |
| (S)-2-Hydroxybutyricacid | 3347-90-8 | 2A-9078787 |
| Methyl6-bromo-2-oxo-2,3,4,8-tetrahydro-1,8-naphthyridine-3-carboxylate | 335031-10-2 | 2A-9078788 |
| 4-[6-(Trifluoromethyl)pyrid-2-yl]-1,2,3,6-tetrahydropyridine | 335267-11-3 | 2A-9078791 |
| Browse all Pharmaceutical Intermediates products » | ||
Phone:
630-322-8886
630-322-8887
Email:
Office Locations:
Chicago, IL, USA
San Francisco, CA, USA
EN
SDS