[CAS NO. 1434639-57-2] ND-646
PRODUCTS SPECIFICATIONS [1434639-57-2]
DESCRIPTION [1434639-57-2]
Overview
| MDL | MFCD30802583 |
|---|---|
| Molecular Weight | 568.64 |
| Molecular Formula | C28H32N4O7S |
| SMILES | O=C(N)C(C)(C)N(C(N(C[C@@H](C1=CC=CC=C1OC)OC2CCOCC2)C3=C4C(C)=C(C5=NC=CO5)S3)=O)C4=O |
6 Publications Citing Use of MCE
Summary
ND-646 is an orally bioavailable and steric inhibitor of acetyl-CoA carboxylase ( ACC ) with IC 50 s of 3.5 nM and 4.1 nM for recombinant hACC1 and hACC2, respectively.
IC50 & Target
IC50: 3.5 nM (hACC1), 4.1 nM (hACC2) [1]
In Vitro
ND-646 inhibits both ACC1 and ACC2 and therefore precludes the ability of ACC2 to compensate for ACC1 inhibition. ND-646 inhibits dimerization of recombinant human ACC2 BC domain (hACC2-BC) under native conditions; hACC2-BC migrates as a dimer in its absence and a monomer in its presence. In cell free systems, ND-646 inhibits enzymatic activity of recombinant human ACC1 (hACC1) with an IC 50 of 3.5 nM and recombinant human ACC2 (hACC2) with an IC 50 of 4.1 nM [1] .
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
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-EIF2α S51 expression observed in tumor lysates [1] .
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
Appearance
Solid
Shipping
Room temperature in continental US; may vary elsewhere.
Storage
| Powder | -20°C | 3 years |
|---|---|---|
| 4°C | 2 years | |
| In solvent | -80°C | 6 months |
| -20°C | 1 month |
Solvent & Solubility
DMSO : ≥ 100 mg/mL ( 175.86 mM )
* "≥" means soluble, but saturation unknown.
Stock Solutions
| Concentration Solvent Mass | 1 mg | 5 mg | 10 mg |
|---|
| 1 mM | 1.7586 mL | 8.7929 mL | 17.5858 mL |
| 5 mM | 0.3517 mL | 1.7586 mL | 3.5172 mL |
| 10 mM | 0.1759 mL | 0.8793 mL | 1.7586 mL |