GNF-2

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

Description:GNF-2 is an allosteric inhibitor of Bcr-abl tyrosine kinase activity (IC50 = 267 nM); inhibits proliferation and induces apoptosis in Bcr-abl-expressing cells. Selective for Bcr-abl over a panel of serine, threonine and tyrosine kinases. Non-ATP-competitive.

Price and Availability

GNF-2, 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#: 401473Name: GNF-2CAS#: 778270-11-4Chemical Formula: C18H13F3N4O2Exact Mass: 374.09906Molecular Weight: 374.32Elemental Analysis: C, 57.76; H, 3.50; F, 15.23; N, 14.97; O, 8.55

Synonym:GNF2; GNF-2; GNF 2.

IUPAC/Chemical Name:3-(6-((4-(trifluoromethoxy)phenyl)amino)pyrimidin-4-yl)benzamide

InChi Key:WEVYNIUIFUYDGI-UHFFFAOYSA-N

InChi Code:InChI=1S/C18H13F3N4O2/c19-18(20,21)27-14-6-4-13(5-7-14)25-16-9-15(23-10-24-16)11-2-1-3-12(8-11)17(22)26/h1-10H,(H2,22,26)(H,23,24,25)

SMILES Code:O=C(N)C1=CC=CC(C2=NC=NC(NC3=CC=C(OC(F)(F)F)C=C3)=C2)=C1

Technical Data

Additional Information

References

1: Fallacara AL, Tintori C, Radi M, Schenone S, BottaM. Insight into the allosteric inhibition of Abl kinase. J Chem InfModel. 2014 May 27;54(5):1325-38. doi: 10.1021/ci500060k. Epub 2014 May8. PubMed PMID: 24787133.

2: Chislock EM, Pendergast AM. Abl family kinases regulate endothelialbarrier function in vitro and in mice. PLoS One. 2013 Dec19;8(12):e85231. doi: 10.1371/journal.pone.0085231. eCollection 2013.PubMed PMID: 24367707; PubMed Central PMCID: PMC3868616.

3: Kim HJ, Yoon HJ, Choi JY, Lee IK, Kim SY. The tyrosine kinaseinhibitor GNF-2 suppresses osteoclast formation and activity. J LeukocBiol. 2014 Feb;95(2):337-45. doi: 10.1189/jlb.0713356. Epub 2013 Oct 15.PubMed PMID: 24130113.

4: Khateb M, Ruimi N, Khamisie H, Najajreh Y, Mian A, Metodieva A,Ruthardt M, Mahajna J. Overcoming Bcr-Abl T315I mutation by combinationof GNF-2 and ATP competitors in an Abl-independent mechanism. BMCCancer. 2012 Nov 27;12:563. doi: 10.1186/1471-2407-12-563. PubMed PMID:23186157; PubMed Central PMCID: PMC3561207.

5: Greuber EK, Pendergast AM. Abl family kinases regulate FcγR-mediatedphagocytosis in murine macrophages. J Immunol. 2012 Dec1;189(11):5382-92. doi: 10.4049/jimmunol.1200974. Epub 2012 Oct 24.PubMed PMID: 23100514; PubMed Central PMCID: PMC3504141.

6: Mian AA, Metodieva A, Badura S, Khateb M, Ruimi N, Najajreh Y,Ottmann OG, Mahajna J, Ruthardt M. Allosteric inhibition enhances theefficacy of ABL kinase inhibitors to target unmutated BCR-ABL andBCR-ABL-T315I. BMC Cancer. 2012 Sep 17;12:411. doi:10.1186/1471-2407-12-411. PubMed PMID: 22985168; PubMed Central PMCID:PMC3488316.

7: Wöhrle FU, Halbach S, Aumann K, Schwemmers S, Braun S, Auberger P,Schramek D, Penninger JM, Laßmann S, Werner M, Waller CF, Pahl HL,Zeiser R, Daly RJ, Brummer T. Gab2 signaling in chronic myeloid leukemiacells confers resistance to multiple Bcr-Abl inhibitors. Leukemia. 2013Jan;27(1):118-29. doi: 10.1038/leu.2012.222. Epub 2012 Aug 3. PubMedPMID: 22858987.

8: Hantschel O. Allosteric BCR-ABL inhibitors in Philadelphiachromosome-positive acute lymphoblastic leukemia: novel opportunitiesfor drug combinations to overcome resistance. Haematologica. 2012Feb;97(2):157-9. doi: 10.3324/haematol.2012.061812. PubMed PMID:22298820; PubMed Central PMCID: PMC3269471.

9: Mian AA, Metodieva A, Najajreh Y, Ottmann OG, Mahajna J, Ruthardt M.p185(BCR/ABL) has a lower sensitivity than p210(BCR/ABL) to theallosteric inhibitor GNF-2 in Philadelphia chromosome-positive acutelymphatic leukemia. Haematologica. 2012 Feb;97(2):251-7. doi:10.3324/haematol.2011.047191. Epub 2011 Nov 4. PubMed PMID: 22058195;PubMed Central PMCID: PMC3269486.

10: Huang WC, Tsai CC, Chen CL, Chen TY, Chen YP, Lin YS, Lu PJ, Lin CM,Wang SH, Tsao CW, Wang CY, Cheng YL, Hsieh CY, Tseng PC, Lin CF.Glucosylceramide synthase inhibitor PDMP sensitizes chronic myeloidleukemia T315I mutant to Bcr-Abl inhibitor and cooperatively inducesglycogen synthase kinase-3-regulated apoptosis. FASEB J. 2011Oct;25(10):3661-73. doi: 10.1096/fj.10-180190. Epub 2011 Jun 24. PubMedPMID: 21705667.

11: Yang J, Campobasso N, Biju MP, Fisher K, Pan XQ, Cottom J, GalbraithS, Ho T, Zhang H, Hong X, Ward P, Hofmann G, Siegfried B, Zappacosta F,Washio Y, Cao P, Qu J, Bertrand S, Wang DY, Head MS, Li H, Moores S, LaiZ, Johanson K, Burton G, Erickson-Miller C, Simpson G, Tummino P,Copeland RA, Oliff A. Discovery and characterization of acell-permeable, small-molecule c-Abl kinase activator that binds to themyristoyl binding site. Chem Biol. 2011 Feb 25;18(2):177-86. doi:10.1016/j.chembiol.2010.12.013. PubMed PMID: 21338916.

12: Kim DH, Sim T. Chemical kinomics: a powerful strategy for targetdeconvolution. BMB Rep. 2010 Nov;43(11):711-9. doi:10.5483/BMBRep.2010.43.11.711. Review. PubMed PMID: 21110913.

13: Hassan AQ, Sharma SV, Warmuth M. Allosteric inhibition of BCR-ABL.Cell Cycle. 2010 Sep 15;9(18):3710-4. doi: 10.4161/cc.9.18.13232. Epub2010 Sep 3. Review. PubMed PMID: 20930519.

14: Deng X, Okram B, Ding Q, Zhang J, Choi Y, Adrián FJ, WojciechowskiA, Zhang G, Che J, Bursulaya B, Cowan-Jacob SW, Rummel G, Sim T, GrayNS. Expanding the diversity of allosteric bcr-abl inhibitors. J MedChem. 2010 Oct 14;53(19):6934-46. doi: 10.1021/jm100555f. PubMed PMID:20828158; PubMed Central PMCID: PMC2951064.

15: Fabbro D, Manley PW, Jahnke W, Liebetanz J, Szyttenholm A, FendrichG, Strauss A, Zhang J, Gray NS, Adrian F, Warmuth M, Pelle X, GrotzfeldR, Berst F, Marzinzik A, Cowan-Jacob SW, Furet P, Mestan J. Inhibitorsof the Abl kinase directed at either the ATP- or myristate-binding site.Biochim Biophys Acta. 2010 Mar;1804(3):454-62. doi:10.1016/j.bbapap.2009.12.009. PubMed PMID: 20152788.

16: Zhang J, Adrián FJ, Jahnke W, Cowan-Jacob SW, Li AG, Iacob RE, SimT, Powers J, Dierks C, Sun F, Guo GR, Ding Q, Okram B, Choi Y,Wojciechowski A, Deng X, Liu G, Fendrich G, Strauss A, Vajpai N,Grzesiek S, Tuntland T, Liu Y, Bursulaya B, Azam M, Manley PW, Engen JR,Daley GQ, Warmuth M, Gray NS. Targeting Bcr-Abl by combining allostericwith ATP-binding-site inhibitors. Nature. 2010 Jan 28;463(7280):501-6.doi: 10.1038/nature08675. Epub 2010 Jan 13. PubMed PMID: 20072125;PubMed Central PMCID: PMC2901986.

17: Mian AA, Oancea C, Zhao Z, Ottmann OG, Ruthardt M. Oligomerizationinhibition, combined with allosteric inhibition, abrogates thetransformation potential of T315I-positive BCR/ABL. Leukemia. 2009Dec;23(12):2242-7. doi: 10.1038/leu.2009.194. Epub 2009 Oct 1. PubMedPMID: 19798092.

18: Choi Y, Seeliger MA, Panjarian SB, Kim H, Deng X, Sim T, Couch B,Koleske AJ, Smithgall TE, Gray NS. N-myristoylated c-Abl tyrosine kinaselocalizes to the endoplasmic reticulum upon binding to an allostericinhibitor. J Biol Chem. 2009 Oct 16;284(42):29005-14. doi:10.1074/jbc.M109.026633. Epub 2009 Aug 13. PubMed PMID: 19679652; PubMedCentral PMCID: PMC2781447.

19: Ohren JF, Sebolt-Leopold JS. Inhibitors of Bcr-abl... breaking newground again. Nat Chem Biol. 2006 Feb;2(2):63-4. PubMed PMID: 16421581.

20: Adrián FJ, Ding Q, Sim T, Velentza A, Sloan C, Liu Y, Zhang G, HurW, Ding S, Manley P, Mestan J, Fabbro D, Gray NS. Allosteric inhibitorsof Bcr-abl-dependent cell proliferation. Nat Chem Biol. 2006Feb;2(2):95-102. Epub 2006 Jan 15. PubMed PMID: 16415863.