Bizelesin

WARNING: This product is for research use only, not for human or veterinary use.

Description:Bizelesin is a synthetic cyclopropylpyrroloindole antineoplastic antibiotic. Bizelesin binds to the minor groove of DNA and induces interstrand cross-linking of DNA, thereby inhibiting DNA replication and RNA synthesis. Bizelesin also enhances p53 and p21 induction and triggers G2/M cell-cycle arrest, resulting in cell senescence without apoptosis.

Price and Availability

Bizelesin, purity > 98%, is not in stock, may be available through custom synthesis. For cost-effective reason, minimum 1 gram order is requested. The product will be characterized by NMR, HPLC and MS analysis. Purity (HPLC) is usually >98%. CoA, QC data, MSDS will be provided when product is successfully made. The estimated lead time is 2-3 months. Please send email to sales@medkoo.com to inquire quote.

Chemical Structure

Theoretical Analysis

MedKoo Cat#: 205951Name: BizelesinCAS#: 129655-21-6Chemical Formula: C43H36Cl2N8O5Exact Mass: 814.21857Molecular Weight: 815.7Elemental Analysis: C, 63.31; H, 4.45; Cl, 8.69; N, 13.74; O, 9.81

Synonym:U77779; U-77779; U 77779; Bizelesin.

IUPAC/Chemical Name:1,3-bis(2-((S)-1-(chloromethyl)-5-hydroxy-8-methyl-1,2,3,6-tetrahydropyrrolo[3,2-e]indole-3-carbonyl)-1H-indol-5-yl)urea

InChi Key:FONKWHRXTPJODV-DNQXCXABSA-N

InChi Code:InChI=1S/C43H36Cl2N8O5/c1-19-15-46-39-33(54)11-31-37(35(19)39)23(13-44)17-52(31)41(56)29-9-21-7-25(3-5-27(21)50-29)48-43(58)49-26-4-6-28-22(8-26)10-30(51-28)42(57)53-18-24(14-45)38-32(53)12-34(55)40-36(38)20(2)16-47-40/h3-12,15-16,23-24,46-47,50-51,54-55H,13-14,17-18H2,1-2H3,(H2,48,49,58)/t23-,24-/m1/s1

SMILES Code:O=C(NC1=CC2=C(NC(C(N3C[C@@H](CCl)C4=C3C=C(O)C5=C4C(C)=CN5)=O)=C2)C=C1)NC6=CC7=C(NC(C(N8C[C@@H](CCl)C9=C8C=C(O)C%10=C9C(C)=CN%10)=O)=C7)C=C6

Technical Data

Additional Information

References

1: Cao PR, McHugh MM, Melendy T, Beerman T. The DNAminor groove-alkylating cyclopropylpyrroloindole drugs adozelesin andbizelesin induce different DNA damage response pathways in human coloncarcinoma HCT116 cells. Mol Cancer Ther. 2003 Jul;2(7):651-9. PubMedPMID: 12883038.

2: Schwartz GH, Patnaik A, Hammond LA, Rizzo J, Berg K, Von Hoff DD,Rowinsky EK. A phase I study of bizelesin, a highly potent and selectiveDNA-interactive agent, in patients with advanced solid malignancies. AnnOncol. 2003 May;14(5):775-82. PubMed PMID: 12702533.

3: Pitot HC, Reid JM, Sloan JA, Ames MM, Adjei AA, Rubin J, BagniewskiPG, Atherton P, Rayson D, Goldberg RM, Erlichman C. A Phase I study ofbizelesin (NSC 615291) in patients with advanced solid tumors. ClinCancer Res. 2002 Mar;8(3):712-7. PubMed PMID: 11895900.

4: McHugh MM, Kuo SR, Walsh-O"Beirne MH, Liu JS, Melendy T, Beerman TA.Bizelesin, a bifunctional cyclopropylpyrroloindole alkylating agent,inhibits simian virus 40 replication in trans by induction of aninhibitor. Biochemistry. 1999 Aug 31;38(35):11508-15. PubMed PMID:10471303.

5: Hidalgo M, Izbicka E, Cerna C, Gomez L, Rowinsky EK, Weitman SD, VonHoff DD. Comparative activity of the cyclopropylpyrroloindole compoundsadozelesin, bizelesin and carzelesin in a human tumor colony-formingassay. Anticancer Drugs. 1999 Mar;10(3):295-302. PubMed PMID: 10327036.

6: Woynarowski JM, Chapman WG, Napier C, Herzig MC. Induction ofAT-specific DNA-interstrand crosslinks by bizelesin in genomic andsimian virus 40 DNA. Biochim Biophys Acta. 1999 Feb 16;1444(2):201-17.PubMed PMID: 10023060.

7: Woynarowski JM, Beerman TA. Effects of bizelesin (U-77,779), abifunctional alkylating minor groove binder, on replication of genomicand simian virus 40 DNA in BSC-1 cells. Biochim Biophys Acta. 1997 Jul17;1353(1):50-60. PubMed PMID: 9256064.

8: Carter CA, Waud WR, Li LH, DeKoning TF, McGovren JP, Plowman J.Preclinical antitumor activity of bizelesin in mice. Clin Cancer Res.1996 Jul;2(7):1143-9. PubMed PMID: 9816280.

9: Volpe DA, Tomaszewski JE, Parchment RE, Garg A, Flora KP, Murphy MJ,Grieshaber CK. Myelotoxic effects of the bifunctional alkylating agentbizelesin on human, canine and murine myeloid progenitor cells. CancerChemother Pharmacol. 1996;39(1-2):143-9. PubMed PMID: 8995512.

10: Woynarowski JM, McHugh MM, Gawron LS, Beerman TA. Effects ofbizelesin (U-77779), a bifunctional alkylating minor groove agent, ongenomic and simian virus 40 DNA. Biochemistry. 1995 Oct10;34(40):13042-50. PubMed PMID: 7548063.

MedKoo，由化学家和药学家陈清奇博士。北卡罗莱纳州的研究三角区（ResearchTrianglePark,简称RTP)，是一家以研发、生产和销售小分子抗癌化合物为主的医药科技公司，该公司的业务范围主要是为全球所有从事抗癌药物研究和开发的制药公司，高校，研究院所，政府相关机构提供与抗癌药物分子相关的产品、试剂和技术服务。

中文名MedKoo中    文美帝药库医药科技公司创立于2008年总部位于美国东海岸

MedKoo是世界领先的供应商之一的抗癌化学试剂和激酶抑制剂。我们制造、销售和分发高质量的抗癌小分子肿瘤学研究试剂。我们的使命是建立世界上最全面的抗癌小分子的集合。我们也为医药行业提供高质量的研究服务、医学研究机构和学术机构。我们致力于提供优质的服务。

MedKoo是世界领先的供应商之一的抗癌化学试剂和激酶抑制剂。我们制造、销售和分发高质量的抗癌小分子肿瘤学研究试剂。我们的使命是建立世界上最全面的抗癌小分子的集合。我们也为医药行业提供高质量的研究服务、医学研究机构和学术机构。我们致力于提供优质的服务和分子有竞争力的价格。MedKoo是您可靠的合作伙伴采购药物发现和药物分子。

MedKoo是世界的抗癌化学试剂和激酶抑制剂供应商之一。我们制造，销售和分销用于肿瘤学研究的高质量抗癌小分子试剂。我们的使命是建立世界上全面的抗癌小分子集合。我们还为制药行业，医学研究组织和学术机构提供高质量的研究服务。我们致力于以具有竞争力的价格提供服务和分子。MedKoo是您可靠的药物发现和药物分子采购合作伙伴。

CRISPR-Cas9是近年兴起的用于靶向基因组特定位置，进行DNA修饰的重要工具。研究发现CRISPR是细菌为了应对病毒的攻击而演化而来的获得性免疫防御机制。具体来说，在CRISPR和Cas9的作用下，经由小RNA分子的引导，靶向并沉默入侵者遗传物质核酸的关键部分。在该系统中，crRNA（CRISPR-derivedRNA）与tracrRNA（trans-activatingRNA）结合形成的复合物能特异性识别靶基因序列，并引导Cas9核酸内切酶在靶定位点剪切双链DNA，随后，细胞的非同源末端连接修复机制（NHEJ）重新连接断裂处的基因组DNA，并引入插入或缺失突变。另外也可以提供一个外源双链供体DNA（Donor）通过同源重组（HR）整合进断裂处的基因组，从而达到对基因组DNA进行修饰的目的。
目前，CRISPR-Cas9系统的高效基因组编辑功能已被应用于多种生物，包括小鼠、大鼠、斑马鱼、秀丽隐杆线虫，也包含多种细菌和植物，甚至在人体上也有应用。