りん酸フルダラビン
フルダラビンホスファート · りん酸フルダラビン · フルダラビンリン酸エステル · 9-(5-O-ホスホノ-β-D-アラビノフラノシル)-2-フルオロ-9H-プリン-6-アミン · 2-フルオロ-9-(5-O-ホスホノ-β-D-アラビノフラノシル)-9H-プリン-6-アミン · フルダラ · 2-フルオロアデニン9-β-D-アラビノフラノシド5'-一りん酸 · 9-(β-D-アラビノフラノシル)-2-フルオロアデニン5'-一りん酸
識別子と物理属性
| CAS No. | 75607-67-9 |
|---|---|
| 分子式 | C10H13FN5O7P |
| 平均分子量 | 365.21 g/mol |
| 単同位体質量 | 365.05366261 g/mol |
| SMILES | Nc1nc(F)nc2c1ncn2[C@@H]1O[C@H](COP(=O)(O)O)[C@@H](O)[C@@H]1O |
| InChIKey | GIUYCYHIANZCFB-FJFJXFQQSA-N |
| PubChem CID | 30751 |
| ChEMBL | CHEMBL1096882 |
| ChEBI | CHEBI:63599 |
| EC No. | 616-242-0 |
| DTXSID | DTXSID2023060 |
| 現地名 | りん酸フルダラビン |
化学・物理的性質
| XLogP | -3.1 |
|---|---|
| 極性表面積 | 186 |
| 水素結合供与体数 | 5 |
| 水素結合受容体数 | 12 |
| 回転可能結合数 | 4 |
| 重原子数 | 24 |
| 形式電荷 | 0 |
| 複雑度 | 514 |
| LogP（分配係数） | -2.8 |
| 溶解度 | 2.97e+00 g/LWater 9.2 (mg/mL)pH 4 buffer 27.6 (mg/mL)pH 9 buffer 57 (mg/mL)DMSO：可溶1mg/mLDMSOまたは水に5mg/mlで可溶 |
| Human Drugs | FDA approved drugs -> Active ingredient |
| 融点 | 260 °C203°C(dec.)(lit.) |
| Optical Rotation | (c = 0.5, H2O) [a]21D = 12 ± 2° |
| Physical Description | Solid |
| Stability/Shelf Life | Bulk: Based on HPLC analysis, the sample is stable for at least one month when stored as the bulk chemical at room temperature and 60 °C. Solution: A 2 mg/mL aqueous solution is stable for at least 48 hours at room temperature and laboratory illumination (HPLC). |
| Collision Cross Section | 168.8 Ų [M+H]+ [CCS Type: TWMethod: calibrated with polyalanine and drug standards] |
| 比旋光度 | [α]D20 +10～+14゜(c=0.5,H2O) |
| 沸点 | 864.2±75.0 °C(Predicted) |
| 密度 | 2.39±0.1 g/cm3(Predicted) |
| 貯蔵条件 | 2-8°C |
| 外観・状態 | 粉 |
| pKa（酸解離定数） | 1.86±0.10(Predicted) |
| 色 | 白い |
| Merck | 14,4126 |
| 安定性 | 吸湿性 |
| InChI | 1S/C10H13FN5O7P/c11-10-14-7(12)4-8(15-10)16(2-13-4)9-6(18)5(17)3(23-9)1-22-24(19,20)21/h2-3,5-6,9,17-18H,1H2,(H2,12,14,15)(H2,19,20,21) |
| InChIKey | GIUYCYHIANZCFB-GFRUICAKSA-N |
| SMILES | Fc1nc2[n](cnc2c(n1)[N+H3])C3OC(C(C3O)O)CO[P](=O)([O-])O |
| CAS データベース | 75607-67-9(CAS DataBase Reference) |
化学的特性
White or almost white, crystalline powder, hygroscopic.
安全性と法規制
| GHS 分類 | DangerH341 (97.6%): Suspected of causing genetic defects [Warning Germ cell mutagenicity]P203, P260, P264, P270, P280, P318, P319, P405, and P501 (click each P-code to see the statement)Aggregated GHS information provided per 82 reports by companies from 8 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies. |
|---|---|
| Hazard Classes and Categories | Muta. 2 (97.6%) |
| 暴露経路 | Bioavailability is 55% following oral administration. |
| 毒性の概要 | Fludarabine phosphate is rapidly dephosphorylated to 2-fluoro-ara-A and then phosphorylated intracellularly by deoxycytidine kinase to the active triphosphate, 2-fluoro-ara-ATP. This metabolite appears to act by inhibiting DNA polymerase alpha, ribonucleotide reductase and DNA primase, thus inhibiting DNA synthesis. The mechanism of action of this antimetabolite is not completely characterized and may be multi-faceted. |
| Carcinogen Classification | No indication of carcinogenicity to humans (not listed by IARC). |
| Drug Induced Liver Injury | Drug Induced Liver Injury Rank (DILIrank 2.0)Fludarabine phosphatevNo-DILI-concernNo matchDOI:10.1016/j.drudis.2016.02.015 |
| Toxicity Data | Mouse(iv): LD50: 1236 mg/kg |
| 水環境危害等級（WGK） | 3 |
| 税関コード | 2934990002 |
| 危険等級 | Muta. 2Repr. 2 |
| 貯蔵分類 | 11 - Combustible Solids |
用途
用途
DNA ポリメラーゼ及び RNA ポリメラーゼを阻害し、DNA/RNA 合成阻害 作用を示します。
説明
Fludarabine phosphate is an antimetabolite indicated for the treatment of B cell lymphocytic leukemia. It is reportedly effective in patients refractory to other therapies. Fludarabine phosphate acts by inhibiting primer RNA synthesis. Its side effects include bone marrow suppression, anemia, thrombocytopenia and neutropenia.
使用
Fludarabine phosphate is used for the treatment of chronic lymphatic leukemia and low-grade lymphoma. In the circulation,fludarabine phosphate is immediately dephosphorylated to the nucleoside fludarabine. About 30-40% of nucleoside fludarabine is excreted into the urine. In addition, fludarabine is metabolized into a hypoxanthine metabolite also excreted in the urine.Intracellularly,fludarabine is stepwise rephosphorylated to the active triphosphate. Deoxycytidine kinase is the dominant, if not the exclusive,enzyme for the formation of the monophosphate. Adenylate kinase and nucleoside diphosphate kinase are believed to be involved in the formation of the diphosphate and triphosphate,respectively.