HA14-1featured
WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#:201460
CAS#:65673-63-4
Description:HA14-1 is a potent Bcl-2 inhibitor with potential anticancer activity. HA14-1 induces apoptosis in various human cancer cells. HA14-1 suppressed NF-kappaB activation through inhibition of phosphorylation and degradation of IkappaBalpha. This inhibition was correlated with suppression of NF-kappaB-dependent gene products (c-myc, cyclin D1, cox-2, and IAP-1). Additionally, HA14-1 also markedly sustained TNF-alpha-mediated JNK activation.
Price and Availability
HA14-1, purity > 98%, is in stock. Current shipping out time is about 2 weeks after order is received. CoA, QC data and MSDS documents are available in one week after order is received.
Chemical Structure
Theoretical Analysis
MedKoo Cat#: 201460Name: HA14-1CAS#: 65673-63-4Chemical Formula: C17H17BrN2O5Exact Mass: 408.03208Molecular Weight: 409.23Elemental Analysis:C, 49.89; H, 4.19; Br, 19.53; N, 6.85; O, 19.55
Synonym:HA-141, HA 141, HA141
IUPAC/Chemical Name:(R)-ethyl 2-amino-6-bromo-4-((R)-1-cyano-2-ethoxy-2-oxoethyl)-4H-chromene-3-carboxylate
InChi Key:SXJDCULZDFWMJC-AAEUAGOBSA-N
InChi Code:InChI=1S/C17H17BrN2O5/c1-3-23-16(21)11(8-19)13-10-7-9(18)5-6-12(10)25-15(20)14(13)17(22)24-4-2/h5-7,11,13H,3-4,20H2,1-2H3/t11-,13-/m0/s1
SMILES Code:O=C(C1=C(N)OC2=C(C=C(Br)C=C2)[C@H]1[C@H](C#N)C(OCC)=O)OCC
Technical Data
Additional Information
HA14-1 is a novel cell-permeable low molecular weight Bcl-2 ligand which antagonizes its function and induces apoptosis. In HL-60 cells 50 µM HA14-1 effectively induced apoptosis associated with loss of mitochondrial membrane potential and activation of caspases -9 and -3.
References
1: Niino S, Nakamura Y, Hirabayashi Y, Nagano-Ito M,Ichikawa S. A small molecule inhibitor of Bcl-2, HA14-1, also inhibitsceramide glucosyltransferase. Biochem Biophys Res Commun. 2013 Feb 26.doi:pii: S0006-291X(13)00312-4. 10.1016/j.bbrc.2013.02.052. [Epub aheadof print] PubMed PMID: 23485465.
2: Akl H, Vandecaetsbeek I, Monaco G, Kauskot A, Luyten T, WelkenhuyzenK, Hoylaerts M, De Smedt H, Parys JB, Bultynck G. HA14-1, but not theBH3 mimetic ABT-737, causes Ca2+ dysregulation in platelets and humancell lines. Haematologica. 2013 Feb 12. [Epub ahead of print] PubMedPMID: 23403318.
3: Nyhan MJ, O"Donovan TR, Elzinga B, Crowley LC, O"Sullivan GC, McKennaSL. The BH3 mimetic HA14-1 enhances 5-fluorouracil-induced autophagy andtype II cell death in oesophageal cancer cells. Br J Cancer. 2012 Feb14;106(4):711-8. doi: 10.1038/bjc.2011.604. Epub 2012 Jan 12. PubMedPMID: 22240779; PubMed Central PMCID: PMC3322956.
4: Weyland M, Manero F, Paillard A, Grée D, Viault G, Jarnet D, Menei P,Juin P, Chourpa I, Benoit JP, Grée R, Garcion E. Mitochondrial targetingby use of lipid nanocapsules loaded with SV30, an analogue of thesmall-molecule Bcl-2 inhibitor HA14-1. J Control Release. 2011 Apr10;151(1):74-82. doi: 10.1016/j.jconrel.2010.11.032. Epub 2010 Dec 5.PubMed PMID: 21138749.
5: Moon DO, Kim MO, Kang SH, Choi YH, Park SY, Kim GY. HA14-1 sensitizesTNF-alpha-induced apoptosis via inhibition of the NF-kappaB signalingpathway: involvement of reactive oxygen species and JNK. Cancer Lett.2010 Jun 1;292(1):111-8. doi: 10.1016/j.canlet.2009.11.014. Epub 2009Dec 22. PubMed PMID: 20022690.
6: Simonin K, Brotin E, Dufort S, Dutoit S, Goux D, N"diaye M, DenoyelleC, Gauduchon P, Poulain L. Mcl-1 is an important determinant of theapoptotic response to the BH3-mimetic molecule HA14-1 in cisplatin-resistantovarian carcinoma cells. Mol Cancer Ther. 2009 Nov;8(11):3162-70. doi:10.1158/1535-7163.MCT-09-0493. Epub 2009 Nov 3. PubMed PMID: 19887550.
7: Mohan N, Karmakar S, Choudhury SR, Banik NL, Ray SK. Bcl-2 inhibitorHA14-1 and genistein together adeptly down regulated survival factorsand activated cysteine proteases for apoptosis in human malignantneuroblastoma SK-N-BE2 and SH-SY5Y cells. Brain Res. 2009 Aug4;1283:155-66. doi: 10.1016/j.brainres.2009.05.097. Epub 2009 Jun 6.PubMed PMID: 19505441; PubMed Central PMCID: PMC3103943.
8: Arisan ED, Kutuk O, Tezil T, Bodur C, Telci D, Basaga H. Smallinhibitor of Bcl-2, HA14-1, selectively enhanced the apoptotic effect ofcisplatin by modulating Bcl-2 family members in MDA-MB-231 breast cancercells. Breast Cancer Res Treat. 2010 Jan;119(2):271-81. doi:10.1007/s10549-009-0343-z. Epub 2009 Feb 24. PubMed PMID: 19238538.
9: Heikaus S, van den Berg L, Kempf T, Mahotka C, Gabbert HE, Ramp U.HA14-1 is able to reconstitute the impaired mitochondrial pathway ofapoptosis in renal cell carcinoma cell lines. Cell Oncol.2008;30(5):419-33. PubMed PMID: 18791273.
10: Hamada N, Kataoka K, Sora S, Hara T, Omura-Minamisawa M, Funayama T,Sakashita T, Nakano T, Kobayashi Y. The small-molecule Bcl-2 inhibitorHA14-1 sensitizes cervical cancer cells, but not normal fibroblasts, toheavy-ion radiation. Radiother Oncol. 2008 Nov;89(2):227-30. doi:10.1016/j.radonc.2008.08.006. Epub 2008 Sep 4. PubMed PMID: 18774194.
11: Kessel D, Price M, Reiners JJ Jr. The Bcl-2 antagonist HA14-1 formsa fluorescent albumin complex that can be mistaken for several oxidizedROS probes. Photochem Photobiol. 2008 Sep-Oct;84(5):1272-6. doi:10.1111/j.1751-1097.2008.00371.x. Epub 2008 May 29. PubMed PMID:18513234; PubMed Central PMCID: PMC2743960.
12: Chernigovskaya EV, Nikitina LS, Dorofeeva NA, Glazova MV. Effects ofselective Bcl-2 inhibitor HA14-1 treatments on functional activity ofmagnocellular vasopressinergic neurons of rat hypothalamus. NeurosciLett. 2008 May 23;437(1):59-64. doi: 10.1016/j.neulet.2008.03.060. Epub2008 Mar 26. PubMed PMID: 18434013.
13: Wlodkowic D, Skommer J, Pelkonen J. Brefeldin A triggers apoptosisassociated with mitochondrial breach and enhances HA14-1- and anti-Fas-mediatedcell killing in follicular lymphoma cells. Leuk Res. 2007Dec;31(12):1687-700. Epub 2007 Apr 10. PubMed PMID: 17428536.
14: Oliver L, Mahé B, Gréé R, Vallette FM, Juin P. HA14-1, a smallmolecule inhibitor of Bcl-2, bypasses chemoresistance in leukaemiacells. Leuk Res. 2007 Jun;31(6):859-63. Epub 2007 Jan 16. PubMed PMID:17224180.
15: Kessel D, Reiners JJ Jr. Initiation of apoptosis and autophagy bythe Bcl-2 antagonist HA14-1. Cancer Lett. 2007 May 8;249(2):294-9. Epub2006 Oct 19. PubMed PMID: 17055152; PubMed Central PMCID: PMC1924967.
16: Separovic D, Wang S, Awad Maitah MY, Hanada K, Kessel D. Ceramideresponse post-photodamage is absent after treatment with HA14-1. BiochemBiophys Res Commun. 2006 Jun 30;345(2):803-8. Epub 2006 May 2. PubMedPMID: 16701558; PubMed Central PMCID: PMC2972543.
17: Manero F, Gautier F, Gallenne T, Cauquil N, Grée D, Cartron PF,Geneste O, Grée R, Vallette FM, Juin P. The small organic compoundHA14-1 prevents Bcl-2 interaction with Bax to sensitize malignant gliomacells to induction of cell death. Cancer Res. 2006 Mar 1;66(5):2757-64.PubMed PMID: 16510597.
18: Wlodkowic D, Skommer J, Pelkonen J. Multiparametric analysis ofHA14-1-induced apoptosis in follicular lymphoma cells. Leuk Res. 2006Sep;30(9):1187-92. Epub 2006 Jan 18. PubMed PMID: 16414117.
19: Skommer J, Wlodkowic D, Mättö M, Eray M, Pelkonen J. HA14-1, a smallmolecule Bcl-2 antagonist, induces apoptosis and modulates action ofselected anticancer drugs in follicular lymphoma B cells. Leuk Res. 2006Mar;30(3):322-31. Epub 2005 Oct 6. PubMed PMID: 16213584.
20: Reiners JJ Jr, Kessel D. Susceptibility of myelomonocytic leukemiaU937 cells to the induction of apoptosis by the non-peptidic Bcl-2ligand HA14-1 is cell cycle phase-dependent. Cancer Lett. 2005 Apr28;221(2):153-63. PubMed PMID: 15808401; PubMed Central PMCID:PMC2965436.
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。
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