|
ChemicalBook Optimization Suppliers |
|
| 化学名: | ボスチニブ | | 英語化学名: | Bosutinib | | 别名: | 4-[(2,4-Dichloro-5-methoxyphenyl)amino]-6-methoxy-7-[3-(4-methyl-1-piperazinyl)propoxy]-3-quinolinecarbonitrile;Bosutinib ( SKI-606 );Bosutinib for research;3-Quinolinecarbonitrile, 4-[(2,4-dichloro-5-Methoxyphenyl)aMino]-6-Methoxy-7-[3-(4-Methyl-1-piperazinyl)propoxy]-;Bosutinib(TINIBS );WAY-173606;Bosulif(bosutinib);4-[(2,4-Dichloro-5-methoxyphenyl)amino]-6-methoxy-7-[3-(4-methyl-1-piperazinyl)propoxy]-3-quinolinecarbonitrile Bosutinib (SKI-606) | | CAS番号: | 380843-75-4 | | 分子式: | C26H29Cl2N5O3 | | 分子量: | 530.45 | | EINECS: | 700-455-1 | | カテゴリ情報: | Aromatics;Heterocycles;Inhibitors;Aromatics Compounds;API;Intermediates & Fine Chemicals;Pfizer compounds;Pharmaceuticals | | Mol File: | 380843-75-4.mol |  |
| 融点 | 116-120 ºC | | 沸点 | 649.7±55.0 °C(Predicted) | | 比重(密度) | 1.36 | | 蒸気圧 | 0-0Pa at 20℃ | | 貯蔵温度 | room temp | | 溶解性 | DMSO: ≥15mg/mL | | 酸解離定数(Pka) | 7.63±0.10(Predicted) | | 外見 | powder | | 色 | off-white to light brown | | 安定性： | Stable for 2 years from date of purchase as supplied. Solutions in DMSO may be stored at -20°C for up to 1 month. | | InChIKey | PICKMQXYAMDEPF-UHFFFAOYSA-N | | LogP | 3.3-4.3 at pH9.5 | | 表面張力 | 72.4mN/m at 3.6mg/L and 20℃ | | CAS データベース | 380843-75-4(CAS DataBase Reference) |
| 主な危険性 | Xi | | Rフレーズ | 36 | | Sフレーズ | 26 | | WGK Germany | 3 | | HSコード | 29335990 |
| | ボスチニブ Usage And Synthesis |
| 用途 | Abl 及び Ser キナーゼの阻害剤です。慢性骨髄性白血病（CML）細胞に対して抗増殖活性を示
します。 | | 効能 | 抗悪性腫瘍薬, チロシンキナーゼ阻害薬 | | 説明 | Bosutinib, similar to dasatinib, was developed as a dual inhibitor of the SCR family of kinases and the ABL kinase, thus applicable for Ph+ leukemias. In September 2012, the US FDA approved bosutinib (also referred to as SKI-607) for the treatment of relapsed or refractory chronicmyeloid leukemia (CML) for patients with resistance or intolerance to prior therapy. | | 化学的特性 | Pale Yellow Solid | | Originator | Wyeth (United States) | | 使用 | Bosutinib (SKI-606) is a novel, dual Src/Abl inhibitor with IC50 of 1.2 nM and 1 nM, respectively. It is built around a chemical scaffold that is different from that of imatinib. peripheral vasolidator increases cerebral blood flow, potential therapeutic for Altzheimer’s disease, cognitive impairment and dementia. | | 使用 | A novel Src kinase inhibitor, suppresses migration and invasion of human breast cancer cells. | | 定義 | ChEBI: Bosutinib is an aminoquinoline that is 4-[(2,4-dichloro-5-methoxyphenyl)amino]-7-[3-(4-methylpiperazin-1-yl)propoxy]quinoline bearing additional cyano and methoxy substituents at positions 3 and 6 respectively. It has a role as an antineoplastic agent and a tyrosine kinase inhibitor. It is a nitrile, a N-methylpiperazine, an aromatic ether, a tertiary amino compound, an aminoquinoline and a dichlorobenzene. | | brand name | Bosulif | | 一般的な説明 | Bosutinib is a safe oral medicine with good bioavailability. It is effective for treating chronic myeloid leukemia (CML). It is also a potent ATP-competitive inhibitor for Src tyrosine kinase. Bosutinib inhibits epidermal growth factor receptor (EGFR). It suppresses solid tumors associated with breast, pancreas and prostate. | | Biochem/physiol Actions | Bosutinib (SKI-606) is an orally active; dual Src/Abl tyrosine kinase inhibitor with potent antiproliferative activity. It does not appear to inhibit c-Kit and PDGRF, which are thought to be the cause of numerous side effects in anticancer treatment with some other tyrosine kinase inhibitors. | | 臨床応用 | Protein kinase inhibitor:
Treatment of Philadelphia chromosome-positive
chronic myelogenous leukaemia resistant or
intolerant to prior therapy | | 副作用 | Possible side effects of bosutinib include Nausea, vomiting, stomach/abdominal pain, loss of appetite, cough, joint pain, headache, or dizziness may occur. If any of these effects last or get worse, tell your doctor or pharmacist promptly. Diarrhea is a common side effect.
www.webmd.com | | 薬物相互作用 | Potentially hazardous interactions with other drugs
Analgesics: possibly increased risk of ventricular
arrhythmias with methadone.
Anti-arrhythmics: possibly increased risk of ventricular
arrhythmias with amiodarone and disopyramide;
concentration possibly increased by dronedarone -
avoid or consider reducing dose of bosutinib.
Antibacterials: concentration possibly increased
by ciprofloxacin, clarithromycin, erythromycin and
telithromycin - avoid or consider reducing dose
of bosutinib; possibly increased risk of ventricular
arrhythmias with moxifloxacin; concentration
reduced by rifampicin and possibly rifabutin - avoid.
Antidepressants: concentration possibly reduced by
St John’s wort - avoid.
Antiepileptics: concentration possibly reduced
by carbamazepine, fosphenytoin, phenobarbital,
phenytoin and primidone - avoid.
Antifungals: concentration increased by ketoconazole
and possibly by fluconazole, itraconazole,
posaconazole and voriconazole - avoid or consider
reducing dose of bosutinib.
Antimalarials: possibly increased risk of
ventricular arrhythmias with chloroquine and
hydroxychloroquine.
Antipsychotics: possibly increased risk of ventricular
arrhythmias with haloperidol; avoid with clozapine,
increased risk of agranulocytosis.
Antivirals: concentration possibly increased by
atazanavir, boceprevir, darunavir, fosamprenavir,
indinavir, ritonavir, saquinavir and telaprevir - avoid
or consider reducing dose of bosutinib; concentration
possibly reduced by efavirenz and etravirine - avoid.
Aprepitant: concentration possibly increased - avoid
or consider reducing dose of bosutinib.
Beta-blockers: possibly increased risk of ventricular
arrhythmias with sotalol.
Bosentan: concentration of bosutinib possibly
reduced - avoid.
Calcium channel blockers: concentration possibly
increased by diltiazem or verapamil - avoid or
consider reducing dose of bosutinib.
Cytotoxics: concentration possibly increased by
imatinib - avoid or consider reducing dose of bosutinib.
Domperidone: avoid concomitant use, risk of
ventricular arrhythmias.
Fosaprepitant: concentration possibly increased by
fosaprepitant - avoid or consider reducing dose of
bosutinib
Grapefruit juice: concentration possibly increased by
grapefruit juice - avoid or consider reducing dose of
bosutinib.
Modafinil: concentration of bosutinib possibly
reduced - avoid. | | 代謝 | Mainly hepatically metabolised. The major circulating
metabolites identified in plasma are oxydechlorinated
(M2) bosutinib (19% of parent exposure) and
N-desmethylated (M5) bosutinib (25% of parent
exposure), with bosutinib N-oxide (M6) as a minor
circulating metabolite. All the metabolites are inactive.
Excretion is mainly via the faeces. | | 貯蔵 | +4°C | | Mode of action | Bosutinib is a synthetic quinolone derivative and dual kinase inhibitor that targets both Abl and Src kinases with potential antineoplastic activity. Unlike imatinib, bosutinib inhibits the autophosphorylation of both Abl and Src kinases, resulting in inhibition of cell growth and apoptosis. Because of the dual mechanism of action, this agent may have activity in resistant CML disease, other myeloid malignancies and solid tumors. Abl kinase is upregulated in the presence of the abnormal Bcr-abl fusion protein which is commonly associated with chronic myeloid leukemia (CML). Overexpression of specific Src kinases is also associated with the imatinib-resistant CML phenotype. | | 参考文献 | Golas et al. (2003), SKI-606, a 4-anilino-3-quinolinecarbonitrile dual inhibitor of Src and Abl kinases, is a potent antiproliferative agent against chronic myelogenous leukemia cells in culture and causes regression of K562 xenografts in nude mice; Cancer Res., 63 375
Remsing Rix et al. (2009), Global target profile of the kinase inhibitor bosutinib in primary chronic myeloid leukemia cells; Leukemia, 23 477
Redaelli et al. (2009), Activity of bosutinib, Dasatinib, and nilotinib against 18 imatinib-resistant BCR/ABL mutants; J. Clin. Oncol., 27 469
MacDonald et al. (2018), Src family kinase inhibitor bosutinib enhances retinoic acid-induced differentiation of HL-60 leukemia cells; Leuk. Lymphoma, 59 2941
Vultur et al. (2008), SKI-606 (bosutinib), a novel Src kinase inhibitor, suppresses migration and invasion of human breast cancer cells; Mol. Cancer Ther., 7 1185 |
|