1. Metabolic Enzyme/Protease
  2. Acetyl-CoA Carboxylase
  3. ND-646

ND-646 

Cat. No.: HY-101842 Purity: 99.53%
Handling Instructions

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.

For research use only. We do not sell to patients.

ND-646 Chemical Structure

ND-646 Chemical Structure

CAS No. : 1434639-57-2

Size Price Stock Quantity
10 mM * 1 mL in DMSO USD 688 In-stock
Estimated Time of Arrival: December 31
1 mg USD 250 In-stock
Estimated Time of Arrival: December 31
5 mg USD 550 In-stock
Estimated Time of Arrival: December 31
10 mg USD 750 In-stock
Estimated Time of Arrival: December 31
25 mg USD 1350 In-stock
Estimated Time of Arrival: December 31
50 mg USD 1950 In-stock
Estimated Time of Arrival: December 31
100 mg USD 2950 In-stock
Estimated Time of Arrival: December 31
200 mg   Get quote  
500 mg   Get quote  

* Please select Quantity before adding items.

Customer Review

Based on 7 publication(s) in Google Scholar

Top Publications Citing Use of Products

    ND-646 purchased from MCE. Usage Cited in: J Neuroinflammation. 2020 Jun 16;17(1):191.

    Western blot analysis of total AMPK, p-AMPK, ACC, p-ACC, α-SMA, SM22α, and GAPDH expression in VSMCs treated as indicated.

    ND-646 purchased from MCE. Usage Cited in: J Neuroinflammation. 2020 Jun 16;17(1):191.

    The level of p-ACC is decreased by exposure to ND-646, with no observable difference in p-AMPK expression. qRT-PCR analysis revealed that α-SMA and SM22α are downregulated in the presence of ND-646, which is corroborated by immunofluorescence labeling.
    • Biological Activity

    • Protocol

    • Purity & Documentation

    • References

    • Customer Review

    Description

    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.

    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 IC50 of 3.5 nM and recombinant human ACC2 (hACC2) with an IC50 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-EIF2αS51 expression observed in tumor lysates[1].

    MCE has not independently confirmed the accuracy of these methods. They are for reference only.

    Molecular Weight

    568.64

    Formula

    C₂₈H₃₂N₄O₇S

    CAS No.

    1434639-57-2

    SMILES

    O=C(N)C(C)(C)N(C(N(C[[email protected]@H](C1=CC=CC=C1OC)OC2CCOCC2)C3=C4C(C)=C(C5=NC=CO5)S3)=O)C4=O

    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
    In Vitro: 

    DMSO : ≥ 100 mg/mL (175.86 mM)

    *"≥" means soluble, but saturation unknown.

    Preparing
    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
    *Please refer to the solubility information to select the appropriate solvent.
    In Vivo:
    • 1.

      Add each solvent one by one:  10% DMSO    40% PEG300    5% Tween-80    45% saline

      Solubility: ≥ 3 mg/mL (5.28 mM); Clear solution

    • 2.

      Add each solvent one by one:  10% DMSO    90% (20% SBE-β-CD in saline)

      Solubility: ≥ 3 mg/mL (5.28 mM); Clear solution

    • 3.

      Add each solvent one by one:  10% DMSO    90% corn oil

      Solubility: ≥ 3 mg/mL (5.28 mM); Clear solution

    *All of the co-solvents are provided by MCE.
    References
    Cell Assay
    [1]

    A549, H460, H157 and H1355 cells are tested for Mycoplasma and are deemed negative. Cells are grown in DMEM plus 10% fetal bovine serum. ACC1-KO clones are maintained in 10% FBS+addition of 200 μM palmitate every 3 days. For proliferation assays via cell counts, cells are plated into 24 well plates in triplicate at 2E4 cells/well and the following day treated with either DMSO vehicle or ND-608 or ND-646. Cell counts are recorded at days 1, 3, 5 and 7-post treatment. For delipidated media, cells are first seeded in media containing regular 10% FBS and the following day are switched into media containing 20% delipidated FBS upon treatment. Viability assays are performed using either a WST-1 viability assay or Cyquant in 96 well culture plates[1].

    MCE has not independently confirmed the accuracy of these methods. They are for reference only.

    Animal Administration
    [1]

    Mice[1]
    Subcutaneous tumor studies: For ACC1-KO studies, 8 week old athymic female nude mice are injected subcutaneously into the hind flanks with 2E6 cells of either WT or ACC1-KO luciferase expressing clones in a volume of 200 μL and imaged by BLI 20 mins after injection. Mice undergo BLI weekly for a period of 42 days (A549) and 49 days (H157), then mice are sacrificed and tumors are dissected and weighed. For ND-646 subcutaneous studies, female athymic nude mice are injected subcutaneously into the hind flanks with 5E6 A549 cells. Tumor growth is measured daily using digital calipers and volumes are calculated. Tumor prevention studies begin at 11 days post tumor cell injection. Mice are randomized into their treatment groups based on similar average tumor volumes. The average tumor volume at the initiation of treatment is 40 mm3. Mice are dosed orally (Per OS) once or twice a day with either a vehicle solution or ND-646 at either 25 mg/kg or 50 mg/kg (0.9% NaCl, 1% Tween 80, 0.5% methylcellulose). At the end of the study, mice are euthanized 1hr post final dose.

    MCE has not independently confirmed the accuracy of these methods. They are for reference only.

    References

    Purity: 99.53%

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    Keywords:

    ND-646ND646ND 646Acetyl-CoA CarboxylaseACC, Acetyl Coenzyme A CarboxylaseInhibitorinhibitorinhibit

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    Cat. No.:
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