Palomid-529featured
WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#:202133
CAS#:914913-88-5
Description:Palomid 529, also known as P529, is a novel PI3K/Akt/mTOR inhibitor. Palomid 529 (P529) inhibits the TORC1 and TORC2 complexes and shows both inhibition of Akt signaling and mTOR signaling similarly in tumor and vasculature. It was demonstrated that P529 inhibited tumor growth, angiogenesis, and vascular permeability. It retained the beneficial aspects of tumor vascular normalization that rapamycin boasts. However, P529 showed the additional benefit of blocking pAktS473 signaling consistent with blocking TORC2 in all cells and thus bypassing feedback loops that lead to increased Akt signaling in some tumor cells. (Source: Cancer Res 008;68(22):9551–7).
Price and Availability
Palomid-529, purity > 98%, is in stock. The same day shipping out after order is received.
Chemical Structure
Theoretical Analysis
MedKoo Cat#: 202133Name: Palomid-529CAS#: 914913-88-5Chemical Formula: C24H22O6Exact Mass: 406.14164Molecular Weight: 406.42788Elemental Analysis:C, 70.92; H, 5.46; O, 23.62
Synonym:Palomid 529; Palomid-529; Palomid529; P529; P 529; P-529.
IUPAC/Chemical Name:8-(1-hydroxyethyl)-2-methoxy-3-((4-methoxybenzyl)oxy)-6H-benzo[c]chromen-6-one
InChi Key:YEAHTLOYHVWAKW-UHFFFAOYSA-N
InChi Code:InChI=1S/C24H22O6/c1-14(25)16-6-9-18-19-11-22(28-3)23(12-21(19)30-24(26)20(18)10-16)29-13-15-4-7-17(27-2)8-5-15/h4-12,14,25H,13H2,1-3H3
SMILES Code:O=C1C2=CC(C(O)C)=CC=C2C3=C(O1)C=C(OCC4=CC=C(OC)C=C4)C(OC)=C3
Technical Data
Additional Information
Phase I trial using Palomid 529. In May, 2011, Paloma Pharmaceuticals accouned that its first-in-class allosteric dual TORC1/TORC2 dissociative inhibitor Palomid 529 has successfully completed the Company’s first three cohorts of its Phase I intravitreal administration trial in patients with age-related macular degeneration (AMD). In addition, the National Eye Institute has treated its first patient in the Institute’s own Phase I AMD trial administering P529 subconjunctival, “A Phase I Unmasked Study to Investigate the Safety and Tolerability of Subconjunctival Injections of Palomid 529 in Patients With Neovascular Age-Related Macular Degeneration.” Both clinical trials have shown preliminary activity. Palomid 529 reduces tumor growth, tumor angiogenesis, and vascular permeability. Palomid 529 (P529), which inhibits the TORC1 and TORC2 complexes and shows both inhibition of Akt signaling and mTOR signaling similarly in tumor and vasculature. We show that P529 inhibits tumor growth, angiogenesis, and vascular permeability. It retains the beneficial aspects of tumor vascular normalization that rapamycin boasts. However, P529 has the additional benefit of blocking pAktS473 signaling consistent with blocking TORC2 in all cells and thus bypassing feedback loops that lead to increased Akt signaling in some tumor cells. (source: Cancer Res. 2008 Nov 15;68(22):9551-7). Palomid 529 (P529) enhances the effect of radiotherapy in prostate cancer. P529 showed a potent antiproliferative activity in the NCI-60 cell lines panel, with growth inhibitory 50 (GI50) <35 microM. In addition, P529 significantly enhanced the antiproliferative effect of radiation in prostate cancer cells (PC-3). Analysis of signalling pathways targeted by P529 exhibited a decrease in p-Akt, VEGF, MMP-2, MMP-9, and Id-1 levels after radiation treatment. Moreover, the Bcl-2/Bax ratio was also reduced. Treatment of PC-3 tumour-bearing mice with 20 mg kg(-1) P529 or 6 Gy radiation dose decreased tumour size by 42.9 and 53%, respectively. Combination of both treatments resulted in 77.4% tumour shrinkage. Decreased tumour growth was due to reduced proliferation and increased apoptosis (as assessed by PCNA and caspase-3 immunostaining). Our results show the antitumour efficacy of P529 alone, and as a radiosensitiser, and suggest that this compound could be used in the future to treat human prostate cancer. (source: Br J Cancer. 2009 Mar 24;100(6):932-40 . Epub 2009 Feb 24.).
References
1: He TY, Tsai LH, Huang CC, Chou MC, Lee H. LKB1Loss at Transcriptional Level Promotes Tumor Malignancy and Poor PatientOutcomes in Colorectal Cancer. Ann Surg Oncol. 2014 May 31. [Epub aheadof print] PubMed PMID: 24879590.
2: Gravina GL, Marampon F, Sherris D, Vittorini F, Di Cesare E,Tombolini V, Lenzi A, Jannini EA, Festuccia C. Torc1/Torc2 inhibitor,Palomid 529, enhances radiation response modulating CRM1-mediatedsurvivin function and delaying DNA repair in prostate cancer models.Prostate. 2014 Jun;74(8):852-68. doi: 10.1002/pros.22804. Epub 2014 Apr8. PubMed PMID: 24715588.
3: Dalal M, Jacobs-El N, Nicholson B, Tuo J, Chew E, Chan CC,Nussenblatt R, Ferris F, Meyerle C. Subconjunctival Palomid 529 in thetreatment of neovascular age-related macular degeneration. Graefes ArchClin Exp Ophthalmol. 2013 Dec;251(12):2705-9. doi:10.1007/s00417-013-2375-7. Epub 2013 May 21. PubMed PMID: 23689994.
4: Lin F, Buil L, Sherris D, Beijnen JH, van Tellingen O. Dual mTORC1and mTORC2 inhibitor Palomid 529 penetrates the blood-brain barrierwithout restriction by ABCB1 and ABCG2. Int J Cancer. 2013 Sep1;133(5):1222-33. doi: 10.1002/ijc.28126. Epub 2013 Apr 1. PubMed PMID:23436212.
5: Syed F, Sherris D, Paus R, Varmeh S, Singh S, Pandolfi PP, Bayat A.Keloid disease can be inhibited by antagonizing excessive mTOR signalingwith a novel dual TORC1/2 inhibitor. Am J Pathol. 2012Nov;181(5):1642-58. doi: 10.1016/j.ajpath.2012.08.006. Epub 2012 Sep 11.Erratum in: Am J Pathol. 2014 Apr;184(4):1253. Singh, Subir [added].PubMed PMID: 22982188.
6: Lin F, Sherris D, Beijnen JH, Van Tellingen O. High-performanceliquid chromatography analysis of a novel small-molecule, anti-cancerdrug, Palomid 529, in human and mouse plasma and in mouse tissuehomogenates. J Chromatogr B Analyt Technol Biomed Life Sci. 2011 Dec15;879(32):3823-31. doi: 10.1016/j.jchromb.2011.10.028. Epub 2011 Oct29. PubMed PMID: 22100549.
7: Gravina GL, Marampon F, Petini F, Biordi L, Sherris D, Jannini EA,Tombolini V, Festuccia C. The TORC1/TORC2 inhibitor, Palomid 529,reduces tumor growth and sensitizes to docetaxel and cisplatin inaggressive and hormone-refractory prostate cancer cells. Endocr RelatCancer. 2011 Jul 1;18(4):385-400. doi: 10.1530/ERC-11-0045. Print 2011Aug. PubMed PMID: 21551258.
8: Xiang T, Jia Y, Sherris D, Li S, Wang H, Lu D, Yang Q. Targeting theAkt/mTOR pathway in Brca1-deficient cancers. Oncogene. 2011 May26;30(21):2443-50. doi: 10.1038/onc.2010.603. Epub 2011 Jan 17. PubMedPMID: 21242970; PubMed Central PMCID: PMC3107712.
9: Lewis GP, Chapin EA, Byun J, Luna G, Sherris D, Fisher SK. Mullercell reactivity and photoreceptor cell death are reduced afterexperimental retinal detachment using an inhibitor of the Akt/mTORpathway. Invest Ophthalmol Vis Sci. 2009 Sep;50(9):4429-35. doi:10.1167/iovs.09-3445. Epub 2009 Apr 15. PubMed PMID: 19369237.
10: Diaz R, Nguewa PA, Diaz-Gonzalez JA, Hamel E, Gonzalez-Moreno O,Catena R, Serrano D, Redrado M, Sherris D, Calvo A. The novel Aktinhibitor Palomid 529 (P529) enhances the effect of radiotherapy inprostate cancer. Br J Cancer. 2009 Mar 24;100(6):932-40. doi:10.1038/sj.bjc.6604938. Epub 2009 Feb 24. PubMed PMID: 19240717; PubMedCentral PMCID: PMC2661786.
11: Xue Q, Hopkins B, Perruzzi C, Udayakumar D, Sherris D, Benjamin LE.Palomid 529, a novel small-molecule drug, is a TORC1/TORC2 inhibitorthat reduces tumor growth, tumor angiogenesis, and vascularpermeability. Cancer Res. 2008 Nov 15;68(22):9551-7. doi:10.1158/0008-5472.CAN-08-2058. PubMed PMID: 19010932; PubMed CentralPMCID: PMC2727940.
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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