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[(1S)-3-methyl-1-[(2R)-3-phenyl-2-(pyrazin-2-ylformamido)propanamido]butyl]boronic acid

ChemBase编号:73
分子式:C19H25BN4O4
平均质量:384.2372
单一同位素质量:384.1968857
SMILES和InChIs

SMILES:
O=C(N[C@H](CC(C)C)B(O)O)[C@H](NC(=O)c1nccnc1)Cc1ccccc1
Canonical SMILES:
CC(C[C@H](B(O)O)NC(=O)[C@H](NC(=O)c1cnccn1)Cc1ccccc1)C
InChI:
InChI=1S/C19H25BN4O4/c1-13(2)10-17(20(27)28)24-18(25)15(11-14-6-4-3-5-7-14)23-19(26)16-12-21-8-9-22-16/h3-9,12-13,15,17,27-28H,10-11H2,1-2H3,(H,23,26)(H,24,25)/t15-,17-/m1/s1
InChIKey:
GXJABQQUPOEUTA-NVXWUHKLSA-N

引用这个纪录

CBID:73 http://www.chembase.cn/molecule-73.html

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名称和登记号

名称和登记号

名称 登记号
IUPAC标准名
[(1S)-3-methyl-1-[(2R)-3-phenyl-2-(pyrazin-2-ylformamido)propanamido]butyl]boronic acid
IUPAC传统名
bortezomib
商标名
Velcade
别名
bortezomib
Bortezomib
CAS号
179324-69-7
PubChem SID
160963536
PubChem CID
93860

数据来源

数据来源

所有数据来源 商品来源 非商品来源
数据来源 数据ID
DrugBank DB00188 external link
PubChem 93860 external link
数据来源 数据ID 价格

理论计算性质

理论计算性质

JChem ALOGPS 2.1
Acid pKa 13.037311  质子受体
质子供体 LogD (pH = 5.5) 1.5302998 
LogD (pH = 7.4) 1.5302991  Log P 1.5303 
摩尔折射率 99.3738 cm3 极化性 40.15836 Å3
极化表面积 124.44 Å2 可自由旋转的化学键
里宾斯基五规则 true 
Log P 0.89  LOG S -3.86 
溶解度 5.32e-02 g/l 

分子性质

分子性质

理化性质 生物活性(PubChem)
溶解度
The solubility of bortezomib, as the monomeric boronic acid, is 3.3 to 3.8 mg/mL in a pH range of 2 to 6.5. expand 查看数据来源

详细说明

详细说明

DrugBank DrugBank
DrugBank -  DB00188 external link
Item Information
Drug Groups approved; investigational
Description Bortezomib (originally PS-341 and marketed as Velcade by Millennium Pharmaceuticals) is the first therapeutic proteasome inhibitor to be tested in humans. It is approved in the U.S. for treating relapsed multiple myeloma and mantle cell lymphoma. In multiple myeloma, complete clinical responses have been obtained in patients with otherwise refractory or rapidly advancing disease.
Indication For treatment of multiple myeloma in patients who have not been successfully treated with at least two previous therapies.
Pharmacology Bortezomib is a drug that inhibits the mammalian 26S proteasome. The ubiquitin-proteasome pathway plays an essential role in regulating the intracellular concentration of specific proteins, thereby maintaining homeostasis within cells. Inhibition of the 26S proteasome prevents this targeted proteolysis, which can affect multiple signaling cascades within the cell. This disruption of normal homeostatic mechanisms can lead to cell death. Experiments have demonstrated that bortezomib is cytotoxic to a variety of cancer cell types in vitro. Bortezomib causes a delay in tumor growth in vivo in nonclinical tumor models, including multiple myeloma. Tumor cells, that is, rapidly dividing cells, appear to be more sensitive to proteasome inhibition.
Toxicity Cardiovascular safety pharmacology studies in monkeys show that lethal IV doses are associated with decreases in blood pressure, increases in heart rate, increases in contractility, and ultimately terminal hypotension. In monkeys, doses of 3.0 mg/m2 and greater (approximately twice the recommended clinical dose) resulted in progressive hypotension starting at 1 hour and progressing to death by 12 to 14 hours following drug administration.
Affected Organisms
Humans and other mammals
Biotransformation In vitro studies with human liver microsomes and human cDNA-expressed cytochrome P450 isozymes indicate that bortezomib is primarily oxidatively metabolized via cytochrome P450 enzymes 3A4, 2C19, and 1A2, while bortezomib metabolism by CYP 2D6 and 2C9 enzymes is minor. The major metabolic pathway is deboronation to form 2 deboronated metabolites that subsequently undergo hydroxylation to several metabolites which are inactive as 26S proteasome inhibitors.
Half Life The mean elimination half-life of bortezomib after first dose ranged from 9 to 15 hours at doses ranging from 1.45 to 2.00 mg/m2 in patients with advanced malignancies.
Protein Binding 83% over the concentration range of 100-1000 ng/ml.
Elimination The pathways of elimination of bortezomib have not been characterized in humans.
Clearance * 102 L/h [patients with multiple myeloma following the first dose for doses of 1 mg/m2]
* 112 L/h [patients with multiple myeloma following the first dose for doses of 1.3 mg/m2]
* 15 - 32 L/h [patients with multiple myeloma following subsequent doses for doses of 1 and 1.3 mg/m2]
References
Adams J, Kauffman M: Development of the proteasome inhibitor Velcade (Bortezomib). Cancer Invest. 2004;22(2):304-11. [Pubmed]
Bonvini P, Zorzi E, Basso G, Rosolen A: Bortezomib-mediated 26S proteasome inhibition causes cell-cycle arrest and induces apoptosis in CD-30+ anaplastic large cell lymphoma. Leukemia. 2007 Apr;21(4):838-42. Epub 2007 Feb 1. [Pubmed]
Voorhees PM, Dees EC, O'Neil B, Orlowski RZ: The proteasome as a target for cancer therapy. Clin Cancer Res. 2003 Dec 15;9(17):6316-25. [Pubmed]
Oakervee HE, Popat R, Curry N, Smith P, Morris C, Drake M, Agrawal S, Stec J, Schenkein D, Esseltine DL, Cavenagh JD: PAD combination therapy (PS-341/bortezomib, doxorubicin and dexamethasone) for previously untreated patients with multiple myeloma. Br J Haematol. 2005 Jun;129(6):755-62. [Pubmed]
External Links
Wikipedia
RxList
Drugs.com

参考文献

参考文献

供应商提供 Google Scholar IconGoogle Scholar PubMed iconPubMed Google Books IconGoogle Books
  • Adams J, Kauffman M: Development of the proteasome inhibitor Velcade (Bortezomib). Cancer Invest. 2004;22(2):304-11. Pubmed
  • Bonvini P, Zorzi E, Basso G, Rosolen A: Bortezomib-mediated 26S proteasome inhibition causes cell-cycle arrest and induces apoptosis in CD-30+ anaplastic large cell lymphoma. Leukemia. 2007 Apr;21(4):838-42. Epub 2007 Feb 1. Pubmed
  • Voorhees PM, Dees EC, O'Neil B, Orlowski RZ: The proteasome as a target for cancer therapy. Clin Cancer Res. 2003 Dec 15;9(17):6316-25. Pubmed
  • Oakervee HE, Popat R, Curry N, Smith P, Morris C, Drake M, Agrawal S, Stec J, Schenkein D, Esseltine DL, Cavenagh JD: PAD combination therapy (PS-341/bortezomib, doxorubicin and dexamethasone) for previously untreated patients with multiple myeloma. Br J Haematol. 2005 Jun;129(6):755-62. Pubmed
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专利

专利

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