ADT-1004
Based on 1 Customer Validation
ADT-1004 is an orally active prodrug of ADT-007 (HY-157887). ADT-007 is a reversible, highly potent and selective pan-RAS inhibitor that binds to the nucleotide-free conformation of RAS proteins and blocks their GTP activation, thereby inhibiting the downstream MAPK and AKT signaling pathways. ADT-1004 can be used for the research of pancreatic ductal adenocarcinoma.
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。
- 純度: 98.16%
- CAS 番号: 1945941-72-9
- 分子式: C33H36FN3O6
- 分子量:589.65
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保管条件:Powder -20°C, 3 years , 4°C, 2 years ; In solvent -80°C, 6 months , -20°C, 1 month
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生物活性
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化学情報
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溶剤 & 溶解度
- 純度とドキュメンテーション
- 参考文献
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Help & FAQs
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GPCR/G Protein Compound Library
HY-L006
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Immunology/Inflammation Compound Library
HY-L007
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Kinase Inhibitor Library
HY-L009
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MAPK Compound Library
HY-L010
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Anti-Cancer Compound Library
HY-L025
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Oxygen Sensing Compound Library
HY-L045
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Ferroptosis Compound Library
HY-L051
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Orally Active Compound Library
HY-L061
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Glutamine Metabolism Compound Library
HY-L064
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Anti-Pancreatic Cancer Compound Library
HY-L077
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Anti-Blood Cancer Compound Library
HY-L079
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Angiogenesis-Related Compound Library
HY-L088
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Anti-Liver Cancer Compound Library
HY-L101
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Anti-Colorectal Cancer Compound Library
HY-L103
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Membrane Protein-targeted Compound Library
HY-L149
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Membrane Receptor-targeted Compound Library
HY-L150
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Highly Selective Inhibitors Library
HY-L158
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Anti-Hematopathy Compound Library
HY-L171
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Bioactive Compound Library Max
HY-L181
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MCE Bioactive Compound Library
HY-L001V
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Bioactive Compound Library
HY-L001
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Cell Proliferation Compound Library
HY-L201
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High-Throughput Bioactive Compound Library
HY-L205
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Lactylation Compound Library
HY-L249
生物活性
ADT-007 (0.1-600 nM; 3 days) potently inhibits the viability of KRASG12C mutant MIA PaCa-2 PDAC cells in vitro with an IC50 of 3.06 nM[1].
ADT-007 (0.1-600 nM; 3 days) potently inhibits the viability of sotorasib/adagrasib-resistant KRASG12C mutant MIA-AMG-R PDAC cells in vitro with an IC50 of 15.59 nM[1].
ADT-007 (5-10 nM; 2 weeks) potently inhibits colony formation of KRASG12C mutant MIA PaCa-2 PDAC cells in vitro at concentrations as low as 5 nM[1].
ADT-007 (5-10 nM; 2 weeks) potently inhibits colony formation of sotorasib/adagrasib-resistant KRASG12C mutant MIA-AMG-R PDAC cells in vitro at concentrations as low as 5 nM[1].
ADT-007 retains growth inhibitory activity against MRTX1133-resistant KRASG12D mutant AsPC-1 PDAC cells in vitro[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
ADT-1004 (40 mg/kg; p.o.; once daily, 5 days per week for 28 consecutive days) inhibits tumor growth, reduces the levels of activated RAS and pERK, and shifts the macrophage population in the tumor microenvironment toward the M1 phenotype in orthotopic KRASG12D-mutant pancreatic ductal adenocarcinoma in C57BL/6J mice[1].
ADT-1004 (40 mg/kg; p.o.; once daily, 5 times per week) inhibits tumor growth, attenuates pERK signaling, reduces stromal αSMA expression, and decreases tumor cell proliferation in subcutaneous KRASG12D, KRASG12C, KRASG12V, and KRASG13Q pancreatic ductal adenocarcinoma PDX models in NSG mice[1].
ADT-1004 (40 mg/kg; p.o.; once daily, 5 days per week for 31 days) inhibits tumor growth of both parental and Sotorasib/Adagrasib-resistant KRASG12C-mutant pancreatic ductal adenocarcinoma in NSG mice and reduces their pERK levels[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:C57BL/6J[1]
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Dosage:10 mg/kg; 20 mg/kg; 30 mg/kg; 40 mg/kg; 50 mg/kg
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Administration:p.o.; once daily; 5x/week; 27 days
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Result:Reduced tumor bioluminescence relative to vehicle across all doses.
Produced statistically significant reductions in tumor weight compared to vehicle or 10 mg/kg dose at 20-50 mg/kg.
Reached average plasma concentrations of active metabolite ADT-007 of 3.4 nM (20 mg/kg), 5.7 nM (30 mg/kg), 31.2 nM (40 mg/kg), and 54.1 nM (50 mg/kg) 6 hours after final dose.
Showed no significant body weight differences between treated and vehicle groups.
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Animal Model:C57BL/6J[1]
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Dosage:40 mg/kg
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Administration:p.o.; once daily; 5x/week; 27 days
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Result:Reduced tumor bioluminescence and tumor weight significantly relative to vehicle.
Reduced activated RAS-GTP levels significantly and reduced pERK levels by ~60% relative to vehicle in tumors.
Reduced density of F4/80+ macrophages, reduced CD206 (M2 marker) expression on F4/80+ macrophages, reduced MHCII expression on F4/80+ macrophages, and increased M1/M2 macrophage ratio in the tumor microenvironment.
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Animal Model:C57BL/6J (female)[1]
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Dosage:20 mg/kg (QD); 20 mg/kg (BID); 40 mg/kg (QD)
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Administration:p.o.; 5x/week
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Result:Produced comparable, significant reductions in tumor bioluminescence and tumor weight relative to vehicle across all dosing regimens.
Showed no significant body weight differences from vehicle.
Reduced activated RAS-GTP levels by ~70% and pERK levels by ~60% relative to vehicle in tumors.
Increased density of CD4+ T cells, CD4+ FoxP3+ Tregs, CD4+ PD-1+ T cells, CD4+ CTLA4+ T cells, CD8+ T cells, CD8+ PD-1+ T cells, CD8+ CTLA4+ T cells, and CD8+ PD-1+ CTLA4+ LAG3+ CD44+ exhausted T cells in the tumor microenvironment.
Increased density of CD103+ dendritic cells, cDC1 dendritic cells, F4/80+ Ly6G+ granulocytic MDSCs, and F4/80+ macrophages with increased MHCII expression, while reducing CD206 expression on F4/80+ macrophages.
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Animal Model:NSG[1]
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Dosage:40 mg/kg
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Administration:p.o.; once daily; 5x/week
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Result:Reduced tumor volume and final tumor weight significantly in all four KRAS-mutant (G12D, G12C, G12V, G13Q) PDX models relative to vehicle.
Showed no significant body weight changes from vehicle.
Reduced pERK levels, αSMA expression, and Ki-67 proliferation marker levels significantly in treated tumors relative to vehicle via IHC analysis.\nReduced tumor volume and final tumor weight significantly in parental KRASG12C MIA PaCa-2 tumors relative to vehicle, with significant reduction in pERK levels.
Produced dramatic reduction in tumor volume and final tumor weight in sotorasib/adagrasib-resistant KRASG12C MIA-AMG-R tumors relative to vehicle, with significant reduction in pERK levels; sotorasib and adagrasib showed no efficacy in this resistant model.
Showed no significant body weight changes between treated and vehicle groups.
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Animal Model:NSG (male)[1]
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Dosage:40 mg/kg
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Administration:p.o.; once daily; 5x/week; 31 days
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Result:Did not significantly affect tumor volume or final tumor weight relative to vehicle.
Showed no significant body weight changes from vehicle.
化学情報
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CAS 番号 1945941-72-9
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性状 Solid
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分子量 589.65
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分子式 C33H36FN3O6
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Color Light yellow to yellow
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SMILES
O=C(NCC1=CC=CO1)CC2=C(C)/C(C3=CC=C(F)C=C32)=C/C4=CC(OC)=C(C(OC)=C4)OC(NC5CCN(CC5)C)=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
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
溶剤 & 溶解度
DMSO : 4.17 mg/mL (7.07 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
濃度 (開始) × 体積 (開始) = 濃度 (終了) × 体積 (終了)
純度とドキュメンテーション
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データシート (284 KB)
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SDS (251 KB)
- English - EN (251 KB)
- Français - FR (251 KB)
- Deutsch - DE (251 KB)
- Norwegian - NO (251 KB)
- Español - ES (251 KB)
- Swedish - SV (251 KB)
- Italian - IT (251 KB)
- Korean - KR (251 KB)
- Portuguese - PT (251 KB)
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取扱説明書 (2659 KB)
参考文献
Complete Stock Solution Preparation Table
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
| Optional Solvent | Concentration Solvent Mass | 1 mg | 5 mg | 10 mg | 25 mg |
|---|---|---|---|---|---|
| DMSO | 1 mM | 1.6959 mL | 8.4796 mL | 16.9592 mL | 42.3980 mL |
| 5 mM | 0.3392 mL | 1.6959 mL | 3.3918 mL | 8.4796 mL |
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