methyl (1R,9R,10S,11R,12R,19R)-11-(acetyloxy)-12-ethyl-4-[(13S,15S,17S)-17-ethyl-17-hydroxy-13-(methoxycarbonyl)-1,11-diazatetracyclo[13.3.1.0^{4,12}.0^{5,10}]nonadeca-4(12),5,7,9-tetraen-13-yl]-8-formyl-10-hydroxy-5-methoxy-8,16-diazapentacyclo[10.6.1.0^{1,9}.0^{2,7}.0^{16,19}]nonadeca-2(7),3,5,13-tetraene-10-carboxylate

• ChemBase编号: 423
• 分子式: C46H56N4O10
• 平均质量: 824.95764
• 单一同位素质量: 824.39964401
• SMILES: O([C@@H]1[C@]2([C@@H]3N(CC[C@@]43[C@@H](N(c3c4cc(c(OC)c3)[C@]3(C[C@H]4C[C@](O)(CN(C4)CCc4c3[nH]c3c4cccc3)CC)C(=O)OC)C=O)[C@@]1(O)C(=O)OC)CC=C2)CC)C(=O)C
• Canonical SMILES: O=CN1c2cc(OC)c(cc2[C@]23[C@@H]1[C@@](O)(C(=O)OC)[C@H](OC(=O)C)[C@]1([C@@H]3N(CC2)CC=C1)CC)[C@]1(C[C@@H]2CN(CCc3c1[nH]c1c3cccc1)C[C@](C2)(O)CC)C(=O)OC
• InChI: InChI=1S/C46H56N4O10/c1-7-42(55)22-28-23-45(40(53)58-5,36-30(14-18-48(24-28)25-42)29-12-9-10-13-33(29)47-36)32-20-31-34(21-35(32)57-4)50(26-51)38-44(31)16-19-49-17-11-15-43(8-2,37(44)49)39(60-27(3)52)46(38,56)41(54)59-6/h9-13,15,20-21,26,28,37-39,47,55-56H,7-8,14,16-19,22-25H2,1-6H3/t28-,37+,38-,39-,42+,43-,44-,45+,46+/m1/s1
• InChIKey: OGWKCGZFUXNPDA-XQKSVPLYSA-N

名称和登记号

名称

• IUPAC标准名: methyl (1R,9R,10S,11R,12R,19R)-11-(acetyloxy)-12-ethyl-4-[(13S,15S,17S)-17-ethyl-17-hydroxy-13-(methoxycarbonyl)-1,11-diazatetracyclo[13.3.1.0^{4,12}.0^{5,10}]nonadeca-4(12),5,7,9-tetraen-13-yl]-8-formyl-10-hydroxy-5-methoxy-8,16-diazapentacyclo[10.6.1.0^{1,9}.0^{2,7}.0^{16,19}]nonadeca-2(7),3,5,13-tetraene-10-carboxylate; methyl (1R,9R,10S,11R,12R,19R)-11-(acetyloxy)-12-ethyl-4-[(13S,15S,17S)-17-ethyl-17-hydroxy-13-(methoxycarbonyl)-1,11-diazatetracyclo[13.3.1.0^4,^1^2.0^5,^1^0]nonadeca-4(12),5,7,9-tetraen-13-yl]-8-formyl-10-hydroxy-5-methoxy-8,16-diazapentacyclo[10.6.1.0^1,^9.0^2,^7.0^1^6,^1^9]nonadeca-2,4,6,13-tetraene-10-carboxylate
• IUPAC传统名: sulfate, vincristine; vincristine sulfate
• 商标名: Oncovin; Vincasar; Vincasar PFS; Vincrex; Vincristine Sulfate PFS; Vinkristin; Marqibo; Onco TCS
• 别名: VCR; VIN; LCR; Leurocristine; 22-Oxovincaleukoblastine; Indole alkaloid; Vincristina [DCIT]; Vincristine Sulfate; Vincristinum [INN-Latin]; Vincrstine; Vincrystine; Z-D-Val-Lys(Z)-OH; vincristine; Vincristine

登记号

• CAS号: 57-22-7
• PubChem SID: 46507033; 160963886
• PubChem CID: 5978
• CHEBI ID: 28445
• ATC码: L01CA02
• CHEMBL: 303560
• Chemspider ID: 5758
• DrugBank ID: DB00541
• KEGG ID: D08679
• 美国药典/FDA物质标识码: 5J49Q6B70F
• 维基百科标题: Vincristine
• Medline Plus: a682822

理论计算性质

JChem

• Acid pKa: 10.849017
• 质子受体: 9
• 质子供体: 3
• LogD (pH = 5.5): -2.3829613
• LogD (pH = 7.4): 1.1448158
• Log P: 3.128179
• 摩尔折射率: 221.4804 cm^3
• 极化性: 87.836975 Å^3
• 极化表面积: 171.17 Å^2
• 可自由旋转的化学键: 10
• 里宾斯基五规则: false

ALOGPS 2.1

• Log P: 3.36
• LOG S: -4.44
• 溶解度: 3.00e-02 g/l

分子性质

理化性质

• 疏水性(logP): 2.8

药理学性质

• 给药途径: Exclusively intravenous
• 生物利用度: n/a
• 排泄: Mostly biliary, 10% in urine
• 半衰期: 19 to 155 hours
• 代谢: Hepatic
• 蛋白结合率: ~75%
• 法定药品分级: Rx-only
• 妊娠期药物分类: D (Australia); D (US)

详细说明

DrugBank - DB00541

• Drug Groups: approved; investigational
• Description: Antitumor alkaloid isolated from Vinca Rosea. (Merck, 11th ed.)
• Indication: For treatment of acute leukaemia, malignant lymphoma, Hodgkin's disease, acute erythraemia, acute panmyelosis
• Pharmacology: Vincristine is a vinca alkaloid antineoplastic agent used as a treatment for various cancers including breast cancer, Hodgkin's disease, Kaposi's sarcoma, and testicular cancer. The vinca alkaloids are structurally similar compounds comprised of 2 multiringed units, vindoline and catharanthine. The vinca alkaloids have become clinically useful since the discovery of their antitumour properties in 1959. Initially, extracts of the periwinkle plant (Catharanthus roseus) were investigated because of putative hypoglycemic properties, but were noted to cause marrow suppression in rats and antileukemic effects in vitro. Vincristine binds to the microtubular proteins of the mitotic spindle, leading to crystallization of the microtubule and mitotic arrest or cell death. Vincristine has some immunosuppressant effect. The vinca alkaloids are considered to be cell cycle phase-specific.
• Toxicity: IVN-RAT LD₅₀ 1300 mg/kg; IPR-MUS LD₅₀ 5.2 mg/kg
• Affected Organisms: Humans and other mammals
• Biotransformation: Hepatic
• Half Life: 19-155 hours
• Protein Binding: ~75%
• References: Graf WD, Chance PF, Lensch MW, Eng LJ, Lipe HP, Bird TD: Severe vincristine neuropathy in Charcot-Marie-Tooth disease type 1A. Cancer. 1996 Apr 1;77(7):1356-62. [Pubmed] ; Qweider M, Gilsbach JM, Rohde V: Inadvertent intrathecal vincristine administration: a neurosurgical emergency. Case report. J Neurosurg Spine. 2007 Mar;6(3):280-3. [Pubmed] ; JOHNSON IS, ARMSTRONG JG, GORMAN M, BURNETT JP Jr: THE VINCA ALKALOIDS: A NEW CLASS OF ONCOLYTIC AGENTS. Cancer Res. 1963 Sep;23:1390-427. [Pubmed]
• External Links: Wikipedia; RxList; Drugs.com

参考文献

• Graf WD, Chance PF, Lensch MW, Eng LJ, Lipe HP, Bird TD: Severe vincristine neuropathy in Charcot-Marie-Tooth disease type 1A. Cancer. 1996 Apr 1;77(7):1356-62. Pubmed
• Qweider M, Gilsbach JM, Rohde V: Inadvertent intrathecal vincristine administration: a neurosurgical emergency. Case report. J Neurosurg Spine. 2007 Mar;6(3):280-3. Pubmed
• JOHNSON IS, ARMSTRONG JG, GORMAN M, BURNETT JP Jr: THE VINCA ALKALOIDS: A NEW CLASS OF ONCOLYTIC AGENTS. Cancer Res. 1963 Sep;23:1390-427. Pubmed