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ND-630 (Firsocostat) (Synonyms: Firsocostat, GS-0976)

Catalog No.GC19261 Copy One-Click Copy Product Info

ND-630 (Firsocostat) is an acetyl-CoA carboxylase (ACC) inhibitor that suppresses the activity of ACC1 (IC50=2.1nM) and ACC2 (IC50=6.1nM).

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ND-630 (Firsocostat) Chemical Structure

Cas No.: 1434635-54-7

Size Price Stock Qty
1mg
$77.00
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5mg
$180.00
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10mg
$288.00
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25mg
$585.00
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50mg
$918.00
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Sample solution is provided at 25 µL, 10mM.



Description of ND-630 (Firsocostat)

ND-630 (Firsocostat) is an acetyl-CoA carboxylase (ACC) inhibitor that suppresses the activity of ACC1 (IC50=2.1nM) and ACC2 (IC50=6.1nM)[1-2]. ND-630 can inhibit fatty acid synthesis, improve insulin sensitivity, and exert beneficial effects on dyslipidemia[3-4].

In vitro, treatment of prostate cancer cells (PC-3, DU145) with ND-630 (5nM) significantly inhibits cell proliferation, migration, and invasion, while reducing fatty acid and triglyceride synthesis[5]. Pretreatment of mouse primary chondrocytes with ND-630 (5nM), followed by culture under high glucose (20mM) and high insulin (20nM) conditions for 7–10 days, significantly inhibits acetyl-CoA carboxylase (ACC) activity, lowers malonyl-CoA levels, and reduces intracellular lipid accumulation[6].

In vivo, oral administration of ND-630 (5mg/kg; twice daily) to Zucker diabetic fatty (ZDF) rats for 37 days significantly reduces hepatic steatosis, improves insulin sensitivity, decreases weight gain without affecting food intake, and has beneficial effects on dyslipidemia[7]. Oral administration of ND-630 (4–16mg/kg/day) to adenine diet-induced chronic kidney disease (CKD) C57BL/6 mice for 4 weeks significantly lowers serum creatinine and blood urea nitrogen levels, alleviates renal tubular injury and collagen deposition, and mitigates oxidative stress and inflammatory responses[8].

References:
[1] Alkhouri N, Lawitz E, Noureddin M, et al. GS-0976 (Firsocostat): an investigational liver-directed acetyl-CoA carboxylase (ACC) inhibitor for the treatment of non-alcoholic steatohepatitis (NASH). Expert Opin Investig Drugs. 2020 Feb;29(2):135-141.
[2] Kwon Y, Gottmann P, Wang S, et al. Induction of steatosis in primary human hepatocytes recapitulates key pathophysiological aspects of metabolic dysfunction-associated steatotic liver disease. J Hepatol. 2025 Jan;82(1):18-27.
[3] Younis IR, Nelson C, Weber EJ, et al. Pharmacokinetics and Safety of Firsocostat, an Acetyl-Coenzyme A Carboxylase Inhibitor, in Participants with Mild, Moderate, and Severe Hepatic Impairment. J Clin Pharmacol. 2024 Jul;64(7):878-886.
[4] Lawitz EJ, Bhandari BR, Ruane PJ, et al. Fenofibrate Mitigates Hypertriglyceridemia in Nonalcoholic Steatohepatitis Patients Treated With Cilofexor/Firsocostat. Clin Gastroenterol Hepatol. 2023 Jan;21(1):143-152.e3.
[5] Wu YP, Zheng WC, Huang Q, et al. ND630 controls ACACA and lipid reprogramming in prostate cancer by regulating the expression of circKIF18B_003. J Transl Med. 2023 Dec 4;21(1):877.
[6] Liu H, Witzigreuter L, Sathiaseelan R, et al. Obesity promotes lipid accumulation in mouse cartilage-A potential role of acetyl-CoA carboxylase (ACC) mediated chondrocyte de novo lipogenesis. J Orthop Res. 2022 Dec;40(12):2771-2779.
[7] Harriman G, Greenwood J, Bhat S, et al. Acetyl-CoA carboxylase inhibition by ND-630 reduces hepatic steatosis, improves insulin sensitivity, and modulates dyslipidemia in rats. Proc Natl Acad Sci U S A. 2016 Mar 29;113(13):E1796-805.
[8] Liu X, Peng Y, Wu S, et al. ND-630, an acetyl-CoA carboxylase inhibitor, prevents renal fibrosis in adenine-induced CKD mice. Naunyn Schmiedebergs Arch Pharmacol. 2025 Sep 3.

Protocol of ND-630 (Firsocostat)

Cell experiment [1]:

Cell lines

Prostate cancer cell lines (PC-3, DU145)

Preparation Method

Prostate cancer cells were maintained in their respective media (F-12K for PC-3, MEM for DU145) supplemented with 10% fetal bovine serum (FBS). Cells were treated with the acetyl-CoA carboxylase (ACC) inhibitor ND-630 at concentrations of 5nM for 48 hours.

Reaction Conditions

5nM; 48 hours

Applications

ND-630 attenuated the enhanced cell proliferation, migration, and invasion induced by circKIF18B_003 overexpression. ND-630 also decreased the expression of fibrosis markers (α-SMA and vimentin) and reduced glucose incorporation into de novo fatty acid synthesis.

Animal experiment [2]:

Animal models

C57BL/6 mice

Preparation Method

Mice were divided into four groups: control, CKD, CKD+ND-630 low-dose (4mg/kg/d), and CKD+ND-630 high-dose (16mg/kg/d). Chronic kidney disease (CKD) was induced by feeding a 0.2% adenine diet for 4 weeks. ND-630 treatment was administered concurrently with CKD induction via oral gavage.

Dosage form

4mg/kg/d and 16mg/kg/d; oral gavage; Daily administration for 4 weeks.

Applications

ND-630 significantly decreased serum creatinine (Scr) and blood urea nitrogen (BUN) levels in adenine-induced CKD mice, with greater efficacy at higher doses. Administration of ND-630 limited renal tubular injury and collagen deposition, suppressed the expression of fibrosis markers (α-smooth muscle actin and vimentin), inhibited ACC1 expression and malonyl-CoA production, and reduced lipid accumulation in the kidneys. Additionally, ND-630 protected against oxidative stress, decreased inflammatory cytokine levels (TNF-α and IL-6), and antagonized TGF-β1/Smad signaling activation in CKD kidneys.

References:
[1] Wu YP, Zheng WC, Huang Q, et al. ND630 controls ACACA and lipid reprogramming in prostate cancer by regulating the expression of circKIF18B_003. J Transl Med. 2023 Dec 4;21(1):877.
[2] Liu X, Peng Y, Wu S, et al. ND-630, an acetyl-CoA carboxylase inhibitor, prevents renal fibrosis in adenine-induced CKD mice. Naunyn Schmiedebergs Arch Pharmacol. 2025 Sep 3.

Chemical Properties of ND-630 (Firsocostat)

Cas No. 1434635-54-7 SDF
Synonyms Firsocostat, GS-0976
Canonical SMILES O=C(C(C(C)=C(C1=NC=CO1)S2)=C2N3C[C@H](OC4CCOCC4)C5=C(OC)C=CC=C5)N(C(C)(C)C(O)=O)C3=O
Formula C28H31N3O8S M.Wt 569.63
Solubility DMSO : ≥ 50 mg/mL (87.78 mM) Storage Store at -20°C
General tips Please select the appropriate solvent to prepare the stock solution according to the solubility of the product in different solvents; once the solution is prepared, please store it in separate packages to avoid product failure caused by repeated freezing and thawing.Storage method and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored at -20°C, please use it within 1 month.
To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time.
Shipping Condition Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request.

Complete Stock Solution Preparation Table of ND-630 (Firsocostat)

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1 mg 5 mg 10 mg
1 mM 1.7555 mL 8.7776 mL 17.5553 mL
5 mM 351.1 μL 1.7555 mL 3.5111 mL
10 mM 175.6 μL 877.8 μL 1.7555 mL
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Average Rating: 5 ★★★★★ (Based on Reviews and 24 reference(s) in Google Scholar.)

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