ND-630 (Firsocostat) (Synonyms: Firsocostat, GS-0976) |
カタログ番号GC19261
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ND-630 (Firsocostat)はアセチル-CoAカルボキシラーゼ（ACC）阻害剤であり、ACC1 (IC50=2.1nM)とACC2 (IC50=6.1nM)の活性を抑制する。
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 1434635-54-7
Sample solution is provided at 25 µL, 10mM.
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ND-630 (Firsocostat)はアセチル-CoAカルボキシラーゼ（ACC）阻害剤であり、ACC1 (IC50=2.1nM)とACC2 (IC50=6.1nM)の活性を抑制する[1-2]。ND-630は脂肪酸の合成を阻害し、インスリンの感受性を改善し、脂質異常症に良い効果を発揮する[3-4]。
体外で、ND-630 (5nM)で前立腺癌細胞（PC-3、DU145）を処理した結果、細胞の増殖、移動と侵入を著しく阻害し、同時に脂肪酸とトリグリセリドの合成を減らす[5]。ND-630 (5nM)でマウス原発性軟骨細胞を事前処理し、続いて高グルコース（20mM）と高インスリン（20nM）の条件下で7-10日間培養した結果、アセチルCoAカルボキシラーゼ（ACC）の活性を著しく阻害し、マロニルCoAのレベルを下げ、細胞内脂質の蓄積を減らす[6]。
体内で、ND-630 (5mg/kg；毎日二回)をZucker糖尿病肥満（ZDF）ラットに37日間経口投与した結果、脂肪肝を著しく減らし、インスリンの感受性を改善し、食物の摂取を影響せずに体重の増加を減らし、脂質異常症に良い効果をもたらす[7]。アデニン食誘発の慢性腎臓疾患（CKD）C57BL/6マウスにND-630 (4–16mg/kg/日)を4週間経口投与した結果、血清クレアチニンと血液尿素窒素のレベルを著しく下げ、腎尿細管損傷とコラーゲン沈着を軽減し、酸化ストレスと炎症反応を緩和した[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.
| 細胞実験[1]: | |
細胞株 | 前立腺癌細胞株（PC-3、DU145） |
準備方法 | 10%のウシ胎児血清（FBS）を添加したそれぞれの培地（PC-3にF-12K、DU145にMEM）で、前立腺癌細胞を培養した。細胞を濃度が5nMのアセチルCoAカルボキシラーゼ（ACC）阻害剤ND-630で48時間処理した。 |
反応条件 | 5nM；48時間 |
アプリケーション | ND-630は、circKIF18B_003の過剰発見による細胞の増殖、移動と侵入の増強を軽減した。ND-630は、線維症マーカー（α-SMAとvimentin）の発見を減らし、de novo脂肪酸の合成へのグルコースの取り込みを減らした。 |
| 動物実験 [2]: | |
動物モデル | C57BL/6マウス |
準備方法 | マウスを四つのグループに分けた：対照群、CKD、低用量のCKD+ND-630(4mg/kg/日)と高用量のCKD+ND-630(16mg/kg/日)。0.2%のアデニン食を4週間投与することで、慢性腎臓疾患（CKD）を誘発した。ND-630を経口投与して、CKD誘発を同時に行った。 |
投与形態 | 4mg/kg/日と16mg/kg/日；経口投与；4週間、毎日投与 |
アプリケーション | ND-630はアデニン誘発のCKDマウスで、血清クレアチニン（Scr）と血液尿素窒素（BUN）のレベルを著しく下げ、より高い用量では効果がより良くなる。ND-630の投与は、腎尿細管損傷とコラーゲン沈着を軽減し、線維症マーカー（α-平滑筋アクチンとvimentin）の発見を抑制し、ACC1の発見とマロニルCoAの生産を阻害し、腎臓で脂質の蓄積を減らした。更に、ND-630は酸化ストレスから守り、炎症サイトカインのレベル（TNF-αとIL-6）を減らし、CKD腎臓でTGF-β1/Smadのシグナル伝達の活性化を拮抗した。 |
References: | |
| Cas No. | 1434635-54-7 | SDF | |
| 同義語 | 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 |
| 溶解度 | 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. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
|
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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Quality Control & SDS
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- Purity: >98.00% Appearance: A solid
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Average Rating: 5 (Based on Reviews and 24 reference(s) in Google Scholar.)