GDC-0879

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

Description:GDC-0879 is a highly selective, potent, and orally bioavailable RAF small-molecule inhibitor. In GDC-0879 -treated mice, both cell line- and patient-derived BRAF(V600E) tumors exhibited stronger and more sustained pharmacodynamic inhibition (>90% for 8 hours) and improved survival compared with mutant KRAS-expressing tumors.

Price and Availability

GDC-0879, 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#: 401470Name: GDC-0879CAS#: 905281-76-7Chemical Formula: C19H18N4O2Exact Mass: 334.14298Molecular Weight: 334.37182Elemental Analysis:C, 68.25; H, 5.43; N, 16.76; O, 9.57

Synonym:GDC0879; GDC-0879; GDC 0879.

IUPAC/Chemical Name:(E)-5-(1-(2-hydroxyethyl)-3-(pyridin-4-yl)-1H-pyrazol-4-yl)-2,3-dihydro-1H-inden-1-one oxime

InChi Key:DEZZLWQELQORIU-RELWKKBWSA-N

InChi Code:InChI=1S/C19H18N4O2/c24-10-9-23-12-17(19(21-23)13-5-7-20-8-6-13)15-1-3-16-14(11-15)2-4-18(16)22-25/h1,3,5-8,11-12,24-25H,2,4,9-10H2/b22-18+

SMILES Code:OCCN1N=C(C2=CC=NC=C2)C(C3=CC4=C(/C(CC4)=N/O)C=C3)=C1

Technical Data

Additional Information

 GDC-0879 is a highly selective, novel potent, orally bioavailable B-Raf inhibitor in various in vitro and cell-based assays with an IC50 estimate of 0.13 nM against purified B-Raf V600E enzyme and a cellular pERK IC50 of 63 nM in the MALME-3M cell line GDC-0879 is a highly selective, novel potent, orally bioavailable B-Raf inhibitor in various in vitro and cell-based assays with an IC50 estimate of 0.13 nM against purified B-Raf V600E enzyme and a cellular pERK IC50 of 63 nM in the MALME-3M cell line

References

1: Mooz J, Oberoi-Khanuja TK, Harms GS, Wang W,Jaiswal BS, Seshagiri S, Tikkanen R, Rajalingam K. Dimerization of thekinase ARAF promotes MAPK pathway activation and cell migration. SciSignal. 2014 Aug 5;7(337):ra73. doi: 10.1126/scisignal.2005484. PubMedPMID: 25097033.

2: Doma E, Rupp C, Varga A, Kern F, Riegler B, Baccarini M. Skintumorigenesis stimulated by Raf inhibitors relies upon Raf functionsthat are dependent and independent of ERK. Cancer Res. 2013 Dec1;73(23):6926-37. doi: 10.1158/0008-5472.CAN-13-0748. Epub 2013 Oct 15.PubMed PMID: 24129679.

3: Coffee EM, Faber AC, Roper J, Sinnamon MJ, Goel G, Keung L, Wang WV,Vecchione L, de Vriendt V, Weinstein BJ, Bronson RT, Tejpar S, XavierRJ, Engelman JA, Martin ES, Hung KE. Concomitant BRAF and PI3K/mTORblockade is required for effective treatment of BRAF(V600E) colorectalcancer. Clin Cancer Res. 2013 May 15;19(10):2688-98. doi:10.1158/1078-0432.CCR-12-2556. Epub 2013 Apr 2. Erratum in: Clin CancerRes. 2013 Jul 15;19(14):4018. PubMed PMID: 23549875; PubMed CentralPMCID: PMC3815598.

4: Fuchs O. Targeting of NF-kappaB signaling pathway, other signalingpathways and epigenetics in therapy of multiple myeloma. CardiovascHematol Disord Drug Targets. 2013 Mar 1;13(1):16-34. Review. PubMedPMID: 23534949.

5: Chou B, Adler RS, Meng M, Percey S, Dean B, Hop CE, Shin YG.Validation and application of a liquid chromatography-tandem massspectrometric method for the determination of GDC-0879 and itsmetabolite in dog plasma using solid phase extraction. J Pharm BiomedAnal. 2012 Nov;70:354-61. doi: 10.1016/j.jpba.2012.05.029. Epub 2012 Jun1. PubMed PMID: 22717139.

6: Hu J, Yu H, Kornev AP, Zhao J, Filbert EL, Taylor SS, Shaw AS.Mutation that blocks ATP binding creates a pseudokinase stabilizing thescaffolding function of kinase suppressor of Ras, CRAF and BRAF. ProcNatl Acad Sci U S A. 2011 Apr 12;108(15):6067-72. doi:10.1073/pnas.1102554108. Epub 2011 Mar 25. PubMed PMID: 21441104; PubMedCentral PMCID: PMC3076888.

7: Hatzivassiliou G, Song K, Yen I, Brandhuber BJ, Anderson DJ, AlvaradoR, Ludlam MJ, Stokoe D, Gloor SL, Vigers G, Morales T, Aliagas I, Liu B,Sideris S, Hoeflich KP, Jaiswal BS, Seshagiri S, Koeppen H, Belvin M,Friedman LS, Malek S. RAF inhibitors prime wild-type RAF to activate theMAPK pathway and enhance growth. Nature. 2010 Mar 18;464(7287):431-5.doi: 10.1038/nature08833. Epub 2010 Feb 3. PubMed PMID: 20130576.

8: Choo EF, Driscoll JP, Feng J, Liederer B, Plise E, Randolph N, ShinY, Wong S, Ran Y. Disposition of GDC-0879, a B-RAF kinase inhibitor inpreclinical species. Xenobiotica. 2009 Sep;39(9):700-9. doi:10.1080/00498250902991827. PubMed PMID: 19552528.

9: Hoeflich KP, Herter S, Tien J, Wong L, Berry L, Chan J, O"Brien C,Modrusan Z, Seshagiri S, Lackner M, Stern H, Choo E, Murray L, FriedmanLS, Belvin M. Antitumor efficacy of the novel RAF inhibitor GDC-0879 ispredicted by BRAFV600E mutational status and sustained extracellularsignal-regulated kinase/mitogen-activated protein kinase pathwaysuppression. Cancer Res. 2009 Apr 1;69(7):3042-51. doi:10.1158/0008-5472.CAN-08-3563. Epub 2009 Mar 10. PubMed PMID: 19276360.

10: Wong H, Belvin M, Herter S, Hoeflich KP, Murray LJ, Wong L, Choo EF.Pharmacodynamics of 2-[4-[(1E)-1-(hydroxyimino)-2,3-dihydro-1H-inden-5-yl]-3-(pyridine-4-yl)-1H-pyrazol-1-yl]ethan-1-ol (GDC-0879), a potent and selective B-Raf kinaseinhibitor: understanding relationships between systemic concentrations,phosphorylated mitogen-activated protein kinase kinase 1 inhibition, andefficacy. J Pharmacol Exp Ther. 2009 Apr;329(1):360-7. doi:10.1124/jpet.108.148189. Epub 2009 Jan 15. PubMed PMID: 19147858.

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。