BiochemProbe — Life Science Research Reagents

ND-646 free base · Synonyms: ND 646 · ND646

ND-646 is an orally bioavailable and steric inhibitor of acetyl-CoA carboxylase.

For research use only. Not for human or veterinary use.

Target Acetyl-CoA Carboxylase
Research area Cancer
Purity >98% Stock Inquire
Data Sheet SDS COA

ND-646 structure

CAS No.: 1434639-57-2

Download structure (.mol)

Pack sizes & pricing

Size Price SKU Stock
250 mg USD 480.00 BP-01889-250mg In stock Get quote
500 mg USD 750.00 BP-01889-500mg In stock Get quote
1 g USD 1,150.00 BP-01889-1g In stock Get quote
5 g Inquire BP-01889-5g Inquire Inquire

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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.

Biological activity

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. 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.

Identifiers

SMILES
COC1=CC=CC=C1[C@H](CN1C2=C(C(C)=C(S2)C2=NC=CO2)C(=O)N(C1=O)C(C)(C)C(N)=O)OC1CCOCC1
InChIKey
HSRWXLIYNCKHRZ-FQEVSTJZSA-N

Specifications

MW (average)
568.6410
Formula
C28H32N4O7S
CAS No.
1434639-57-2
Physical state
Solid
Color
white to off-white
Shipping
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage
Powder -20℃ 2 years; In solvent -20℃ 1 month;

Solubility

Soluble in DMSO

Documents

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.

Same target

Search Acetyl-CoA Carboxylase

Same research area

Search Cancer