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NCT-501

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Chemical Structure| 1802088-50-1 同义名 : -
CAS号 : 1802088-50-1
货号 : A802123
分子式 : C21H32N6O3
纯度 : 98%
分子量 : 416.517
MDL号 : MFCD29472261
存储条件：

粉末 Sealed in dry,2-8°C

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 3 mg/mL(7.2 mM)，配合低频超声，并水浴加热至45℃助溶，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO
动物实验配方：
生物活性
靶点

  • Dehydrogenase

    ALDH1A1, IC50:40 nM
描述 The human genome encodes 19 aldehyde dehydrogenase (ALDH) enzymes that metabolize reactive aldehydes to their corresponding carboxylic acid derivatives. Unbalanced biological activity of ALDHs and specific contribution to their metabolism pathway have been associated in a variety of disease states, including alcoholic liver disease, type 2 hyperprolinemia, hyperammonemia, Parkinson’s disease, and cancers [3]. NCT-501 is a potent and selective theophylline-based inhibitor of aldehyde dehydrogenase 1A1 (ALDH1A1), inhibits hALDH1A1 with IC50 of 40 nM, typically shows better selectivity over other ALDH isozymes and other dehydrogenases (hALDH1B1, hALDH3A1, and hALDH2, IC50 >57 μM) [3]. In vitro, NCT-501 shows a 16% decrease in the Cal-27 CisR cell line at 20 nM concentration, though the difference was not statistically significant [4]. The permeability measured in Caco-2 cell line indicates that NCT-501 exhibits excellent permeability and does not seem to be a substrate of transporters, such as P-gp [3]. Reasonable volume of distribution (Vss = 1.8 L/kg) but short half-life (t1/2 < 1 h) and high clearance level (CL = 98 mL min−1 kg−1) indicate that 64 is well absorbed and distributed but rapidly metabolized and/or excreted. This is consistent with the finding of short t1/2 of CD1 mouse liver microsomal stability (17 min, multipoint format) [3]. NCT-501 (100 µg/animal; i.t.; every alternate day for 20 days) shows a 78% inhibition in tumor growth in Cal-27 CisR derived xenografts [5].
作用机制 NCT-501 is substrate noncompetitive inhibitor, which bind near the solvent exposed exit of substrate-binding site [3].
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

2.40mL

0.48mL

0.24mL

12.00mL

2.40mL

1.20mL

24.01mL

4.80mL

2.40mL
参考文献

[1]Kulsum S, Sudheendra HV, et al. Cancer stem cell mediated acquired chemoresistance in head and neck cancer can be abrogated by aldehyde dehydrogenase 1 A1 inhibition. Mol Carcinog. 2017 Feb;56(2):694-711.

[2]Yang SM, Yasgar A, et al. Discovery of NCT-501, a Potent and Selective Theophylline-Based Inhibitor of Aldehyde Dehydrogenase 1A1 (ALDH1A1). J Med Chem. 2015 Aug 13;58(15):5967-78.

[3] Yang SM. Discovery of NCT-501, a Potent and Selective Theophylline-Based Inhibitor of Aldehyde Dehydrogenase 1A1 (ALDH1A1). J Med Chem. 2015 Aug 13;58(15):5967-78. doi: 10.1021/acs.jmedchem.5b00577. Epub 2015 Jul 24.

[4]Kulsum S. Cancer stem cell mediated acquired chemoresistance in head and neck cancer can be abrogated by aldehyde dehydrogenase 1 A1 inhibition. Mol Carcinog. 2017 Feb;56(2):694-711. doi: 10.1002/mc.22526.

[5] Kulsum S. Cancer stem cell mediated acquired chemoresistance in head and neck cancer can be abrogated by aldehyde dehydrogenase 1 A1 inhibition. Mol Carcinog. 2017 Feb;56(2):694-711. doi: 10.1002/mc.22526.