| HIV-1 integrase inhibitorUesful for anti-HIV |
Sample solution is provided at 25 µL, 10mM.
Nature.2017 Jan 19;541(7637):417-420.
Nature.2018 Nov;563(7731):407-411.Nature.2018 Jun 13.Nature.2018 Jun 27.Nature.2018 Mar 29;555(7698):673-677.Nature.2017 Sep 7;549(7670):96-100.Nature.2016 Apr 21;532(7599):398-401.
Science.2016 Aug 5;353(6299)594-8Nat Nanotechnol.2017 Dec;12(12):1190-1198.Nature Biotechnology.2017 Jun;35(6):569-576Nat Med.2018 Sep 17.Cell.2018 Dec 21. pii: S0092-8674(18)31561-7.Cell.Available online 25 October 2018.Cell.2018 Sep 27. pii: S0092-8674(18)31183-8.Cell.2018 Jun 28;174(1):172-186.e21.Cell.2018 Feb 22;172(5):1007-1021.e17.Cell.2017 Nov 30;171(6):1284-1300.e21.Cell.2017 Aug 17. pii: S0092-8674(17)30869-3.Cell.2017 Jul 13;170(2):312-323Nat Med.2018 Jan 29.Nat Med.2017 Nov;23(11):1342-1351.Cell.2017 Apr 6;169(2):286-300.Cell.2015 Aug 27;162(5):987-1002.Cell.2015 Feb 12;160(4):729-44.Nature Medicine.2017 Apr;23(4):493-500.Cancer Cell.2018 May 14;33(5):905-921.e5.Cancer Cell.2018 Apr 9;33(4):752-769.e8.Cancer Cell.2018 Mar 12;33(3):401-416.e8.Cancer Cell.2017 Aug 14;32(2):253-267.e5.Nat Methods.2018 Jul;15(7):523-526.Cell Stem Cell.2018 May 3;22(5):769-778.e4.Cell Stem Cell.2017 Nov 20. pii: S1934-5909(17)30375-2.Quality Control & MSDS
- View current batch:
- Purity = 98.00%
- COA (Certificate Of Analysis)
- MSDS (Material Safety Data Sheet)
- Datasheet
Chemical structure
| Description | HIV-1 integrase inhibitor is an inhibitor of HIV-1 integrase used for anti-HIV. | |||||
| Targets | HIV-1 integrase | |||||
| IC50 | ||||||
HIV-1 integrase inhibitor Dilution Calculator
calculate
HIV-1 integrase inhibitor Molarity Calculator
calculate
| Cas No. | 544467-07-4 | SDF | Download SDF |
| Chemical Name | (Z)-4-[3-(azidomethyl)phenyl]-4-hydroxy-2-oxobut-3-enoic acid | ||
| Canonical SMILES | C1=CC(=CC(=C1)CN=[N+]=[N-])C(=CC(=O)C(=O)O)O | ||
| Formula | C11H9N3O4 | M.Wt | 247.21 |
| Solubility | Soluble in DMSO | Storage | Store at -20°C |
| Shipping Condition | Evaluation sample solution : ship with blue ice.All other available size:ship with RT , or blue ice upon request | ||
| General tips | For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months. | ||
HIV-1 integrase inhibitor is useful for anti-HIV, with IC50 value of 0.33 µM,[1] which can target HIV-1 integrase and depress the activity in the treatment of HIV infection, AIDS, and other similar diseases characterized by integration of a retroviral genome into a host chromosome.HIV integrase is a 32 kDa protein produced from the C-terminal portion of the Pol gene product, an enzyme produced by HIV that enables its genetic material to be integrated into the DNA of the infected cell [2]which are not to be confused with phage integrases and a key component in the retroviral pre-integration complex (PIC)[3]. HIV-1 integrase is composed of 3 structurally independent, functional domains: the N-terminal domain (NTD), catalytic core domain (CCD) and the C-terminal domain (CTD).The HIV-1 integration occurs through a multistep process that includes two catalytic reactions: 3’endonucleolytic processing of proviral DNA ends (termed 3’processing) and integration of 3’-processed viral DNA into cellular DNA (referred to as strand transfer)[4].The human immunodeficiency virus (HIV) is the causative agent for the acquired immunodeficiency syndrome (AIDS)[5], then HIV integrase is an attractive target for new anti-HIV drugs. The drug design of HIV-1 integrase inhibitor include integrase strand transfer inhibitors (INSTIs),inhibition of the LEDGF/p75- integrase interaction and integrase binding inhibitors, but strand transfer inhibition is the most intuitively obvious and readily pursued to date.Mg2+ and Mn2+ are critical cofactors in the integration phase, so removing these cofactors (e.g. through chelation) causes functional impairment of integrase[6].Competitive inhibitors compete directly with viral DNA for binding to integrase in order to inhibit 3‘-end processing.[7] In doing this the inhibitors completely block the active site from binding to target DNA.INSTIs bind tightly and specifically to the IN that is associated with the ends of the DNA by chelating the divalent metal ions (Mg2+) which is coordinated by the catalytic triad, such as the DDE motif which is located in the CCD and is the active site of the enzyme[8].Development of a successful INSTI treatment was accomplished when raltegravir was discovered by Merck Sharp & Dohme Limited.[9] S/GSK1349572 is an integrase inhibitor discovered by ViiV/Shinongi which was entering phase three in clinical trials in 2011. This new drug is promising and seems to be well tolerated and so far shows better results than both raltegravir and elvitegravir.[10]References:1.Loizidou EZ et al. Analysis of binding parameters of HIV-1 integrase inhibitors: correlates of drug inhibition and resistance. Bioorg Med Chem. 2009, 17(13):4806-18.2.Cocohoba, J; Dong, BJ. "Raltegravir: the first HIV integrase inhibitor". Clinical therapeutics.2008, 30(10): 1747–65.3.Mouscadet, JF; Delelis, O; Marcelin, AG; Tchertanov, L. "Resistance to HIV-1 integrase inhibitors: A structural perspective". Drug resistance updates : reviews and commentaries in antimicrobial and anticancer chemotherapy.2010, 13(4-5):139–50.4.Fan, X; Zhang, FH.et al."Design of HIV-1 integrase inhibitors targeting the catalytic domain as well as its interaction with LEDGF/p75: a scaffold hopping approach using salicylate and catechol groups". Bioorganic & Medicinal Chemistry.2011,19 (16): 4935–52.5.Pommier, Yves.et al. "Integrase inhibitors to treat HIV/Aids". Nature Reviews Drug Discovery.2005, 4 (3): 236–248.6.Pendri, A.et al. "New first and second generation inhibitors of human immunodeficiency virus-1 integrase". Expert opinion on therapeutic patents. 2011,21 (8): 1173–89.7.Chen, X; Tsiang, M, Yu, F, Hung, M, Jones, GS, Zeynalzadegan, A, Qi, X, Jin, H, Kim, CU, Swaminathan, S, Chen, JM. "Modeling, analysis, and validation of a novel HIV integrase structure provide insights into the binding modes of potent integrase inhibitors". Journal of Molecular Biology. 2008, 380 (3): 504–19.8.Mouscadet, JF. et al."Resistance to HIV-1 integrase inhibitors: A structural perspective". Drug resistance updates : reviews and commentaries in antimicrobial and anticancer chemotherapy.2010,13(4-5):139–50.9.McColl, DJ; Chen, X. "Strand transfer inhibitors of HIV-1 integrase: bringing IN a new era of antiretroviral therapy". Antiviral Research,. 2010,85 (1): 101–18.10.Barnhart, Matthew,James Shelton."A better state of ART improving antiretroviral regimens to increase global access to HIV treatment". Journal of AIDS and HIV Research. 2011, 3 (4): 71–78.
ebiomall.com
>
>
>
>
>
>
>
>
>
>
>
>
逆转录（reverse transcription）是以RNA为模板合成DNA的过程，即RNA指导下的DNA合成。是RNA病毒的复制形式，需逆转录酶的催化。艾滋病病毒(HIV)就是一种典型的逆转录病毒。
逆转录与反转录严格意义上来说没有什么区别，但是逆转录是RNA类病毒自主行为，在整合到宿主细胞内以RNA为模板形成DNA的过程；反转录是进行基因工程过程中，人为地提取出所需要的目的基因的信使RNA，并以之为模板人工合成DNA的过程。二者虽同为RNA→DNA的过程，但地点不同，相对性的来说，逆转录在体内，反转录在体外。
2、取灭过菌且无核酸酶的0.2ml离心管，依次加入2～5μgRNAnμL
3、65℃保温5min，然后冰浴5min；
4、往3步骤中的0.2ml离心管依次加入下列组份
RNase抑制剂（40u/μL）0.5μL
10×M-MLVReactionBuffer2μL
DTT（200mM）1μL
逆转录酶（M-MLV）1μL
5、轻轻混匀后，然后2000rpm离心20s；
6、先在37℃保温1hr，然后70℃保温15min；
7、上述产物可立即进行下一步的PCR反应或-20℃保存。向左转|向右转
在进行RT反应之前，应考虑以下几个方面：
1、RNA
成功的cDNA合成来自高质量的RNA，高质量的RNA至少应保证全长并且不含逆转录酶的抑制剂，如EDTA或SDS。在提取RNA的过程中，要特别防止RNase的污染，同时在逆转录反应中经常加入RNase抑制剂以增加cDNA合成的长度和产量。RNase抑制剂要在第一链cDNA合成反应中，在缓冲液和还原剂（如DTT）存在的条件下加入，因为cDNA合成前的过程会使抑制剂变性，从而释放结合的可以降解RNA的RNase。蛋白RNase抑制剂仅防止RNaseA，B，C对RNA的降解，并不能防止皮肤上的RNase，因此尽管使用了这些抑制剂，也要小心不要从手指上引入RNase，实验过程中经常更换新手套。
2、引物的选择
OligodT
选择OligodT时，要求RNA必须有PolyA，所以真核生物的mRNA都适用。适合长链甚至全长mRNA的RT，所以对RNA样品的质量要求较高，最好不要有明显的DNA污染、RNA降解和RNA断裂。假如想探索新的mRNA进行RT反应，建议推荐使用OligodT引物。使用OligodT引物要比随机引物和特异性引物的稳定性要好。
随机引物
适合各种RNA的RT，尤其适合模板丰度很低的情况（比如某个gene表达量很低）。选择随机引物时，第一链cDNA合成反应中就是以所有的RNA为模板，然后进行PCR反应时设计引物进行特异性扩增。同时要注意随机引物的量和总RNA量之间的关系，一般建议每5μg总RNA的随机引物的用量为50ng，如果每5μg总RNA的随机引物的用量超过250ng，可能会导致小片段产物（<500bp）的增加和长片断、全长产物产物的降低。
特异性引物
特异性引物只能用你设计引物时的下游引物做RT，引物设计质量影响RT的结果，而且不同引物退火温度本来就不相同，所以按照说明书按照一个温度做不是最佳选择，一般不推荐。向左转|向右转
