ABS-752
ABS-752 is an orally active prodrug targeting CRBN-modulating molecular glue with selectivity in protein degradation. ABS-752 preferentially degrades GSPT1 and induces cytotoxicity through this degradation, while it also degrades NEK7, SALL4 and CK1α, with weaker degradation potency against CK1α. As a prodrug, ABS-752 requires metabolic activation to ABT-002 to form the active complex; VAP-1 mediates its conversion to an aldehyde intermediate. ABS-752 induces cell death, reduces cell viability, and exhibits antitumor activity, leading to regression and inhibition of tumor growth. ABS-752 shows no cytotoxicity in primary human hepatocytes. ABS-752 can be used in the research of hepatocellular carcinoma.
商品は「研究用試薬」です。人や動物の医療用・臨床診断用・食品用の製品ではありません。
研究用途以外に使用した場合、当社は一切の責任を負いかねます。
- CAS 番号: 2761170-84-5
- 分子式: C14H14FN3O3
- 分子量:291.28
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保管条件:
Please store the product under the recommended conditions in the Certificate of Analysis.
To place orders, for customer services and technical support, please contact: MedChemExpress USA
Tel: 609-228-6898 E-mail: [email protected] [email protected]
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生物活性
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化学情報
- 純度とドキュメンテーション
- 参考文献
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Help & FAQs
Eukaryotic Release Factor (eRF) アイソフォーム固有の製品をすべて表示
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生物活性
製品説明
IC50 & Target
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eRF3a/GSPT1 1 nM (DC50, Hep3B, 24 h) |
NEK7 9 nM (DC50, Hep3B, 24 h) |
体外実験
ABS-752 (72 h) exerts cytotoxic/cytostatic activity in 13 of 19 tested HCC cell lines, reducing viability by at least 50%[1].
ABS-752 (1-50 μM; 72 h) reduces viability in wild-type Hep3B cells, but has no effect on Hep3B GSPT1G575N cells, demonstrating that GSPT1 degradation drives its cytotoxic activity[1].
ABS-752 (0.1 nM-30 μM; 72 h) has viability-reducing activity in Hep3B cells that is dependent on VAP-1[1].
ABS-752 (6 h, 24 h) potently degrades GSPT1 (DC50=1 nM at 24 h), NEK7 (DC50=9 nM at 24 h), CK1α (DC50=35 nM at 24 h) in Hep3B cells, and SALL4 (DC50=40 nM at 24 h) in Kelly cells, with GSPT1 as the primary target showing near-complete degradation at early time points[1].
ABS-752 (0.1 μM; 6 h) preferentially degrades GSPT1, with greater degradation of NEK7 than CK1α[1].
ABS-752 (1-10 μM) does not form a biochemical ternary complex with CRBN and GSPT1, NEK7, CK1α, or IKZF1, but shows recruitment activity with SALL4[1].
ABS-752 (10 μM; 0-20 h) is converted to the aldehyde metabolite ABT-971 by recombinant mVAP-1[1].
ABS-752 (125-2500 μM; 15 min) is oxidized by recombinant human VAP-1 with a Km of 674 μM[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:wild-type Hep3B cells, CRISPR-engineered Hep3B GSPT1 G575N (degradation-resistant) cells
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Concentration:1 nM-50 μM
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Incubation Time:72 h
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Result:Potently reduced viability in wild-type Hep3B cells.
Had no effect on the viability of Hep3B GSPT1 G575N cells.
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Cell Line:Hep3B cells
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Concentration:10 μM PXS-4728A; 0.1 nM-30 μM ABS-752
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Incubation Time:1 h (PXS-4728A pre-incubation); 72 h (ABS-752 co-incubation)
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Result:Pre-treatment with PXS-4728A abolished the viability-reducing activity of ABS-752 in Hep3B cells.
The activity of control compound CC-90009 was unaffected by PXS-4728A pre-treatment.
体内実験
ABS-752 (100 mg/kg; p.o.; BID; 20-21 days) induces tumor growth inhibition in 80% of tested HCC PDX models, with >50% TGI in four models and complete regression in one model at the 100 mg/kg BID dose[1].
ABS-752 (0.1 mg/kg; single dose) induces significant degradation of GSPT1 and NEK7 in non-human primates at a 0.1 mg/kg dose, with ~80% GSPT1 degradation observed 6 hours post-dose[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:NSG mice (female)[1]
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Dosage:10 mg/kg; 3 mg/kg; 1 mg/kg
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Administration:p.o.; BID; 14 days
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Result:Induced strong tumor growth regression, with complete eradication in some animals at 10 mg/kg.
Induced remarkable tumor growth inhibition at 3 mg/kg and 1 mg/kg.
Confirmed strong degradation of GSPT1 in tumors excised 2 and 4 hours post-dose.
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Animal Model:BALB/c nude mice (female)[1]
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Dosage:100 mg/kg
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Administration:p.o.; BID; 20-21 days
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Result:Inhibited tumor growth in 8/10 models, with tumor growth inhibition (TGI) ranging from 16-100%.
Achieved >50% TGI in four models, including complete tumor regression in the LI6643 model by day 15-16.
Induced strong tumor growth control in the LI0050, LI0752, and LI1069 models.
化学情報
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CAS 番号 2761170-84-5
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分子量 291.28
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分子式 C14H14FN3O3
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SMILES
O=C(C(N(CC1=C2C=C(F)C(CN)=C1)C2=O)CC3)NC3=O
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輸送条件
Room temperature in continental US; may vary elsewhere.
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保管条件
Please store the product under the recommended conditions in the Certificate of Analysis.
純度とドキュメンテーション
参考文献
Calculators
濃度 (開始) × 体積 (開始) = 濃度 (終了) × 体積 (終了)
ABS-752 関連分類
HY-W599279 関連分類
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