Tarloxotinib bromide (TH-4000) (Synonyms: TH-4000) |
| カタログ番号GC32100 |
臭化タルロキソチニブ（Tarloxotinib bromide (TH-4000)）はEGFR/HER2の非可逆的阻害剤プロドラッグである。
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 1636180-98-7
Sample solution is provided at 25 µL, 10mM.
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臭化タルロキソチニブ（Tarloxotinib bromide (TH-4000)）はEGFR/HER2の非可逆的阻害剤プロドラッグである。乳癌の低酸素微小環境（＜0.1％O2）では、臭化タルロキソチニブはTH-4000Eに変換される。TH-4000Eは、HER2二量体のリン酸化とその下流の経路を阻害し、活性酸素依存的な機序によってHER2陽性乳がん細胞にアポトーシスを誘導する。
臭化タルロキソチニブ（0-10μM；2時間）は、A431細胞において201nMのIC50でpEGFRを阻害した。このことは、タルロキソチニブは細胞内のEGFR、HER2、HER4に対してはあまり効果がなく、非腫瘍組織では標的活性を生じないことを示唆している。
臭化タルロキソチニブ（50mg/kg、20％m/vの2-ヒドロキシプロピル-b-シクロデキストリン中、i.p.、週1回、21日間）は、マウスのHCC-1954腫瘍の増殖を阻害し、トラスツズマブ耐性乳房腫瘍においてラパチニブよりも高い有効性を示す。タルロキソチニブ臭化物はまた、細胞増殖の低下を示すKi67陽性領域を減少させる。
References:
[1]. Estrada-Bernal A, Le AT, et,al. Tarloxotinib Is a Hypoxia-Activated Pan-HER Kinase Inhibitor Active Against a Broad Range of HER-Family Oncogenes. Clin Cancer Res. 2021 Mar 1;27(5):1463-1475. doi: 10.1158/1078-0432.CCR-20-3555. Epub 2020 Dec 22. PMID: 33355298; PMCID: PMC7926264.
[2]. Shao X, Yang D, et,al. TH-4000, a hypoxia-activated pan-HER inhibitor, shows excellent preclinical efficacy for the treatment of HER2+ breast cancer. Arch Toxicol. 2024 Mar;98(3):865-881. doi: 10.1007/s00204-023-03670-6. Epub 2024 Jan 11. PMID: 38212449.
[3]. Maddox AL, Brehove MS, et,al. Molecular Assessment of HER2 to Identify Signatures Associated with Therapy Response in HER2-Positive Breast Cancer. Cancers (Basel). 2022 Jun 4;14(11):2795. doi: 10.3390/cancers14112795. PMID: 35681773; PMCID: PMC9179327
[4].Phillips RM. Targeting the hypoxic fraction of tumours using hypoxia-activated prodrugs. Cancer Chemother Pharmacol. 2016 Mar;77(3):441-57. doi: 10.1007/s00280-015-2920-7. Epub 2016 Jan 25. PMID: 26811177; PMCID: PMC4767869.
| 細胞実験[1]: | |
細胞株 | A431細胞（WT EGFR発現細胞） |
準備方法 | 細胞株を指定のチロシンキナーゼ阻害剤で2時間処理した。 |
反応条件 | 0-10μM; 2時間 |
アプリケーション | 臭化タルロキソチニブは、A431細胞において201 nMのIC50でpEGFRを阻害した。 |
| 動物実験 [2]: | |
動物モデル | 雌性BALB/cヌードマウス（HCC-1954細胞腫瘍モデル） |
準備方法 | マウスを対照群と治療群に無作為に割り付けた。投与レジメンは以下の通り：対照群にはコーン油を投与し、ラパチニブ群（コーン油中50mg/kg）は週3回、21日間経口投与した。臭化タルロキソチニブ群（50mg/kgを20％m/vの2-ヒドロキシプロピル-β-シクロデキストリンに溶解）には腹腔内注射を週1回、21日間行った。 |
投与形態 | 50mg/kg、20%m/v 2-ヒドロキシプロピル-β-シクロデキストリン中；i.p；週1回、21日間 |
アプリケーション | 臭化タルロキソチニブはマウスHCC-1954腫瘍の増殖を阻害する。 |
参考文献: [1]: Estrada-Bernal A, Le AT, et,al. Tarloxotinib Is a Hypoxia-Activated Pan-HER Kinase Inhibitor Active Against a Broad Range of HER-Family Oncogenes. Clin Cancer Res. 2021 Mar 1;27(5):1463-1475. doi: 10.1158/1078-0432.CCR-20-3555. Epub 2020 Dec 22. PMID: 33355298; PMCID: PMC7926264. [2]: Shao X, Yang D, et,al. TH-4000, a hypoxia-activated pan-HER inhibitor, shows excellent preclinical efficacy for the treatment of HER2+ breast cancer. Arch Toxicol. 2024 Mar;98(3):865-881. doi: 10.1007/s00204-023-03670-6. Epub 2024 Jan 11. PMID: 38212449. | |
| Cas No. | 1636180-98-7 | SDF | |
| 同義語 | TH-4000 | ||
| Canonical SMILES | BrC1=C(Cl)C=CC(NC2=NC=NC3=C2C=C(NC(/C=C/C[N+](C)(C)CC4=C([N+]([O-])=O)N=CN4C)=O)N=C3)=C1.[Br-] | ||
| Formula | C24H24Br2ClN9O3 | M.Wt | 681.77 |
| 溶解度 | DMSO : ≥ 33 mg/mL (48.40 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. | ||
| Prepare stock solution | |||
|
1 mg | 5 mg | 10 mg |
| 1 mM | 1.4668 mL | 7.3339 mL | 14.6677 mL |
| 5 mM | 293.4 μL | 1.4668 mL | 2.9335 mL |
| 10 mM | 146.7 μL | 733.4 μL | 1.4668 mL |
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Quality Control & SDS
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- Purity: >98.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 39 reference(s) in Google Scholar.)
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