|
|
| | 6-CHLORO-2,3,4,9-TETRAHYDRO-1H-CARBAZOLE-1-CARBOXAMIDE Basic information |
| Product Name: | 6-CHLORO-2,3,4,9-TETRAHYDRO-1H-CARBAZOLE-1-CARBOXAMIDE | | Synonyms: | 6-CHLORO-2,3,4,9-TETRAHYDRO-1H-CARBAZOLE-1-CARBOXAMIDE;6-CHLORO-2,3,4,9-TETRAHYDRO-1H-CARBAZOLE-1-CARBOXAMIDE, >95%;(S)-6-chloro-2,3,4,9-tetrahydro-1H-carbazole-1-carboxamide;SEN0014196;6-Chloro-2,3,4,9-tetrahydro-1H-carbazole-1-carboxamide EX-527 Selisistat;EX 527, >=98%;EX 527 (Selisistat);Selisistat 6-Chloro-2,3,4,9-tetrahydro-1H-carbazole-1-carboxaMide | | CAS: | 49843-98-3 | | MF: | C13H13ClN2O | | MW: | 248.71 | | EINECS: | | | Product Categories: | Inhibitors;Inhibitor;Other enzyme inhibitors and activators | | Mol File: | 49843-98-3.mol |  |
| | 6-CHLORO-2,3,4,9-TETRAHYDRO-1H-CARBAZOLE-1-CARBOXAMIDE Chemical Properties |
| Melting point | 179.0 to 183.0 °C | | Boiling point | 531.7±38.0 °C(Predicted) | | density | 1.388 | | storage temp. | 2-8°C | | solubility | Soluble in dimethyl sulfoxide, ethanol and dimethyl formamide. | | form | powder | | pka | 16.12±0.40(Predicted) | | color | white to beige | | Stability: | Stable for 2 years from date of purchase as supplied. Solutions in DMSO or ethanol may be stored at -20°C for up to 3 months |
| Hazard Codes | Xn | | Risk Statements | 22-36 | | Safety Statements | 26 | | RIDADR | UN 2811 6.1 / PGIII | | WGK Germany | 3 | | HS Code | 2933998090 |
| | 6-CHLORO-2,3,4,9-TETRAHYDRO-1H-CARBAZOLE-1-CARBOXAMIDE Usage And Synthesis |
| Description | EX-527 (49843-98-3) is a selective SIRT1 inhibitor (IC50=98 nM). Does not inhibit other HDACs or SIRT family members. Increases p53 acetylation following DNA damage. Cell permeable. | | Uses | A selective inhibitor of SIRT1 over SIRT2 and SIRT3 | | Uses | EX-527 has been used:
- in 1% dimethyl sulfoxide, 30%, polyethylene glycol-400 and 1% Tween 80 for treating C57BL/6 N mice to study its effect on intestinal morphological changes and crypt cell apoptosis
- as a an inhibitor of sirtuin 1, in treating human cancer lines MCF-7 (Michigan cancer foundation-7) and HCT116 (colon cancer cell line) incubated in Dulbecco′s modified Eagle′s medium, to study its effect on mitochondrial ATP (adenosine triphosphate) production
- Intracerebroventricularly infused in rat model of epileptogenesis, to access kainic acid–induced status epilepticus stimulated sirtuin 1 activity
| | Uses | EX-527 is a potent and selective sirtuin 1 (SIRT1) inhibitor (IC50 38 nM) identified from a high throughput screen. EX-527 is more selective (200-500-fold) for SIRT1 than for SIRT2 or SIRT3 and has been shown to be a potent SIRT6 inhibitor using H3K56 deacetylation site based substrate. EX-527 does not inhibit class I/II HDAC activity at concentrations up to 100uM. Enhances p53 acetylation in response to DNA damaging agents. EX-527 is racemic; the active isomer (EX-243) gives similar results and potency whereas the other isomer (designated EX-242) is inactive. | | Definition | ChEBI: 6-chloro-2,3,4,9-tetrahydro-1H-carbazole-1-carboxamide is a member of the class of carbazoles that is 2,3,4,9-tetrahydro-1H-carbazole which is substituted at position 1 by an aminocarbohyl group and at position 6 by a chlorine. It is a member of carbazoles, a monocarboxylic acid amide and an organochlorine compound. | | General Description | A cell-permeable indole compound that acts as a potent and highly selective inhibitor of SIRT1 (IC50 = 98 nM). It inhibits other sirtuin family deacetylases only at much higher concentrations (IC50 = 19.6 and 48.7 μM for SIRT2 and SIRT3, respectively) and shows no inhibitory effect against class I and II HDACs or NAD glycohydrolase even at concentrations as high as 100 μM. Shown to be orally bioavailable with a serum half-life of 136 minutes in mice in vivo. | | Biological Activity | Selective inhibitor of SIRT1 that does not inhibit histone deacetylase (HDAC) or other sirtuin deacetylase family members (IC 50 values are 98, 19600, 48700, > 100000 and > 100000 nM for SIRT1, SIRT2, SIRT3, HDAC and NADase respectively). Enhances p53 acetylation in response to DNA damaging agents. | | Biochem/physiol Actions | Primary TargetSIRT1 | | storage | Store at +4°C | | References | 1) Napper et al. (2005), Discovery of indoles as potent and selective inhibitors of the deacetylase SIRT1; J. Med. Chem., 48 8045
2) Solomon et al. (2006) Inhibition of SIRT1 catalytic activity increases p53 acetylation but does not alter cell survival following DNA damage; Mol. Cell, 26 28
3) Gertz et al. (2013) EX-527 inhibits Sirtuins by exploiting their unique NAD+-dependent deacetylation mechanism; Proc. Natl. Acad. Sci. USA, 110 e2772 |
| | 6-CHLORO-2,3,4,9-TETRAHYDRO-1H-CARBAZOLE-1-CARBOXAMIDE Preparation Products And Raw materials |
|