| Identification | Back Directory | [Name]
2-[(4-chloro-3-nitrophenyl)sulphonyl]anthranilic acid | [CAS]
68003-38-3 | [Synonyms]
Einecs 268-121-3
SLC25A1 inhibitor CTPI-2
2-(4'-Chloro-3'-nitrobenzenesulfonamido)benzoic acid
2-[(4-chloro-3-nitrophenyl)sulphonyl]anthranilic acid
Benzoic acid, 2-(((4-chloro-3-nitrophenyl)sulfonyl)amino)-
2-(4-Chloro-3-nitrophenylsulfonylamino)benzenecarboxylic acid | [EINECS(EC#)]
268-121-3 | [Molecular Formula]
C13H9ClN2O6S | [MDL Number]
MFCD00129907 | [MOL File]
68003-38-3.mol | [Molecular Weight]
356.74 |
| Chemical Properties | Back Directory | [Boiling point ]
564.8±60.0 °C(Predicted) | [density ]
1.660±0.06 g/cm3(Predicted) | [storage temp. ]
Store at -20°C | [solubility ]
DMSO:125 mg/mL(350.40 mM) | [form ]
A solid | [pka]
3.19±0.36(Predicted) | [color ]
Off-white to light yellow | [InChI]
1S/C13H9ClN2O6S/c14-10-6-5-8(7-12(10)16(19)20)23(21,22)15-11-4-2-1-3-9(11)13(17)18/h1-7,15H,(H,17,18) | [InChIKey]
NJTHPOSQGFJTDP-UHFFFAOYSA-N | [SMILES]
[S](=O)(=O)(Nc2c(cccc2)C(=O)O)c1cc(c(cc1)Cl)[N+](=O)[O-] | [EPA Substance Registry System]
Benzoic acid, 2-[[(4-chloro-3-nitrophenyl)sulfonyl]amino]- (68003-38-3) |
| Hazard Information | Back Directory | [Uses]
CTPI-2 is a third-generation mitochondrial citrate carrier SLC25A1 inhibitor with a KD of 3.5 μM. CTPI-2 inhibits glycolysis, PPARγ, and its downstream target the glucose transporter GLUT4. CTPI-2 halts salient alterations of NASH reverting steatosis, preventing the evolution to steatohepatitis, reducing inflammatory macrophage infiltration in the liver and adipose tissue, and starkly mitigating obesity induced by a high-fat diet. Antitumor activity[1][2]. | [Biological Activity]
CTPI-2 is a selective mitochondrial citrate transporter (SLC25A1) inhibitor th at displays H1299 anti-proliferation activity in a SLC25A1-dependent manner (IC50 <10 μM). When compared with CTPI-1CTPI-2 exhibits 20-fold higher target affinity (hSLC25A1 KD = 3.5 μM vs. 63.6 μMrespectively) and is ~1000-fold more potent against H1299 sphere-forming capacity. CTPI-2 inhibits mitochondrial respiration and formation of patient NSCLC tumors-derived CSCs spheres in cultures (10-50 μM)as well as suppresses the growth of patent-derived NSCLC exnografts in mice in vivo (28 mg/kg q.o.d. i.p.). | [in vivo]
CTPI-2 is a unique regulator of glycolysis that limits the metabolic plasticity of cancer stem cells (CSCs). CTPI-2 (26 mg/kg; i.p.) inhibits tumor growth in in vivo models of non-small cell lung cancer (NSCLC)[1].
CTPI-2 (50 mg/kg; i.p.; alternate days for 12 weeks) completely averts weight gain in the prevention study and leads to significant weight loss in the reversion study[2].
CTPI-2 prevents steatohepatitis and normalizes glucose tolerance. CTPI-2 lowers the levels of circulating IL-6 while increasing anti-inflammatory IL-4 and IL-10 and also reduced the monocyte chemoattractant protein-1 and monokine-induced by interferon-γ that attract neutrophils and monocytes. CTPI-2 regulates the citrate pool, the lipogenic and the gluconeogenic pathways[2]. | Animal Model: | C57BL/6J mice (HFD-fed mice)[2] | | Dosage: | 50 mg/kg | | Administration: | Alternate days via the intraperitoneal route for 12 weeks | | Result: | Completely averted weight gain in the prevention study and led to significant weight loss in the reversion study.
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| [References]
[1] Tan M, et al. Inhibition of the mitochondrial citrate carrier, Slc25a1, reverts steatosis, glucose intolerance, and inflammation in preclinical models of NAFLD/NASH. Cell Death Differ. 2020;27(7):2143-2157. DOI:10.1038/s41418-020-0491-6
[2] Fernandez HR, et al. The mitochondrial citrate carrier, SLC25A1, drives stemness and therapy resistance in non-small cell lung cancer. Cell Death Differ. 2018;25(7):1239-1258. DOI:10.1038/s41418-018-0101-z |
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