| Identification | Back Directory | [Name]
ND-646 | [CAS]
1434639-57-2 | [Synonyms]
ND-646
CPD5077
ND646;ND 646
2-[1-[(2R)-2-(2-methoxyphenyl)-2-(oxan-4-yloxy)ethyl]-5-methyl-6-(1,3-oxazol-2-yl)-2,4-dioxo-1H,2H,3H,4H-thieno[2,3-d]pyrimidin-3-yl]-2-methylpropanamide
1,4-Dihydro-1-[(2R)-2-(2-methoxyphenyl)-2-[(tetrahydro-2H-pyran-4-yl)oxy]ethyl]-α,α,5-trimethyl-6-(2-oxazolyl)-2,4-dioxothieno[2,3-d]pyrimidine-3(2H)-acetamide
Thieno[2,3-d]pyrimidine-3(2H)-acetamide, 1,4-dihydro-1-[(2R)-2-(2-methoxyphenyl)-2-[(tetrahydro-2H-pyran-4-yl)oxy]ethyl]-α,α,5-trimethyl-6-(2-oxazolyl)-2,4-dioxo-
(R)-2-(1-(2-(2-methoxyphenyl)-2-((tetrahydro-2H-pyran-4-yl)oxy)ethyl)-5-methyl-6-(oxazol-2-yl)-2,4-dioxo-1,4-dihydrothieno[2,3-d]pyrimidin-3(2H)-yl)-2-methylpropanamide | [Molecular Formula]
C28H32N4O7S | [MDL Number]
MFCD30802583 | [MOL File]
1434639-57-2.mol | [Molecular Weight]
568.64 |
| Chemical Properties | Back Directory | [Boiling point ]
801.8±75.0 °C(Predicted) | [density ]
1.40±0.1 g/cm3(Predicted) | [storage temp. ]
Store at -20°C | [solubility ]
DMF: 30 mg/ml; DMSO: 30 mg/ml; DMSO:PBS (pH 7.2) (1:4): 0.20 mg/ml; Ethanol: 20 mg/ml | [form ]
A solid | [pka]
15.52±0.50(Predicted) | [color ]
White to off-white |
| Hazard Information | Back Directory | [Uses]
ND-646 is an orally bioavailable and steric inhibitor of acetyl-CoA carboxylase (ACC) with IC50s of 3.5 nM and 4.1 nM for recombinant hACC1 and hACC2, respectively. | [in vivo]
To explore the impact of chronic ND-646 treatment on NSCLC tumor growth and to determine the efficacy of twice-daily dosing, athymic nude mice bearing established A549 subcutaneous tumors are treated orally with either vehicle twice daily (BID), 25 mg/kg ND-646 once daily (QD), 25 mg/kg ND-646 BID or 50 mg/kg ND-646 QD for 31 days. ND-646 at 25 mg/kg QD is ineffective at inhibiting tumor growth. However, ND-646 administered at 25 mg/kg BID or 50 mg/kg QD significantly inhibits subcutaneous A549 tumor growth. ND-646 is well tolerated throughout the treatment period, with no significant weight loss occurring after chronic ND-646 dosing, suggesting that the maximum tolerated dose (MTD) has not been reached. Mice are sacrificed at 1 hr post final dose and tissues are either prepared for immunohistochemistry (IHC) or immunoblot analysis. Tumors treated with all doses of ND-646 have lost detection of P-ACC at 1 hr, demonstrating effective tumor penetration and acute ACC inhibition by ND-646. Notably, only at the doses of ND-646 that lead to significant tumor growth inhibition (25 mg/kg BID and 50 mg/kg QD) is significant elevation of P-EIF2αS51 expression observed in tumor lysates[1]. | [storage]
Store at -20°C | [References]
[1] Svensson RU, et al. Inhibition of acetyl-CoA carboxylase suppresses fatty acid synthesis and tumor growth of non-small-cell lung cancer in preclinical models. Nat Med. 2016 Oct;22(10):1108-1119. DOI:10.1038/nm.4181 |
|
|