GNF-2
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    WARNING: This product is for research use only, not for human or veterinary use.

MedKoo CAT#: 401473

CAS#: 778270-11-4

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

Size
Price

100mg
USD 750
1g
USD 3250
Size
Price

200mg
USD 1250
2g
USD 4650
Size
Price

500mg
USD 2150
5g
USD 6750

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

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Theoretical Analysis

MedKoo Cat#: 401473
Name: GNF-2
CAS#: 778270-11-4
Chemical Formula: C18H13F3N4O2
Exact Mass: 374.09906
Molecular Weight: 374.32
Elemental 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

Appearance:
Solid powder

Purity:
>98% (or refer to the Certificate of Analysis)

Shipping Condition:
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition:
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility:
Soluble in DMSO, not in water

Shelf Life:
>2 years if stored properly

Drug Formulation:
This drug may be formulated in DMSO

Stock Solution Storage:
0 - 4 C for short term (days to weeks), or -20 C for long term (months).

Harmonized System Code:
293490


Additional Information

  
 
 
 


References

1: Fallacara AL, Tintori C, Radi M, Schenone S, Botta M. Insight into the allosteric inhibition of Abl kinase. J Chem Inf Model. 2014 May 27;54(5):1325-38. doi: 10.1021/ci500060k. Epub 2014 May 8. PubMed PMID: 24787133.

2: Chislock EM, Pendergast AM. Abl family kinases regulate endothelial barrier function in vitro and in mice. PLoS One. 2013 Dec 19;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 kinase inhibitor GNF-2 suppresses osteoclast formation and activity. J Leukoc Biol. 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 combination of GNF-2 and ATP competitors in an Abl-independent mechanism. BMC Cancer. 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-mediated phagocytosis in murine macrophages. J Immunol. 2012 Dec 1;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 the efficacy of ABL kinase inhibitors to target unmutated BCR-ABL and BCR-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 leukemia cells confers resistance to multiple Bcr-Abl inhibitors. Leukemia. 2013 Jan;27(1):118-29. doi: 10.1038/leu.2012.222. Epub 2012 Aug 3. PubMed PMID: 22858987.

8: Hantschel O. Allosteric BCR-ABL inhibitors in Philadelphia chromosome-positive acute lymphoblastic leukemia: novel opportunities for drug combinations to overcome resistance. Haematologica. 2012 Feb;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 the allosteric inhibitor GNF-2 in Philadelphia chromosome-positive acute lymphatic 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 myeloid leukemia T315I mutant to Bcr-Abl inhibitor and cooperatively induces glycogen synthase kinase-3-regulated apoptosis. FASEB J. 2011 Oct;25(10):3661-73. doi: 10.1096/fj.10-180190. Epub 2011 Jun 24. PubMed PMID: 21705667.

11: Yang J, Campobasso N, Biju MP, Fisher K, Pan XQ, Cottom J, Galbraith S, 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, Lai Z, Johanson K, Burton G, Erickson-Miller C, Simpson G, Tummino P, Copeland RA, Oliff A. Discovery and characterization of a cell-permeable, small-molecule c-Abl kinase activator that binds to the myristoyl 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 target deconvolution. 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. Epub 2010 Sep 3. Review. PubMed PMID: 20930519.

14: Deng X, Okram B, Ding Q, Zhang J, Choi Y, Adrián FJ, Wojciechowski A, Zhang G, Che J, Bursulaya B, Cowan-Jacob SW, Rummel G, Sim T, Gray NS. Expanding the diversity of allosteric bcr-abl inhibitors. J Med Chem. 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, Fendrich G, Strauss A, Zhang J, Gray NS, Adrian F, Warmuth M, Pelle X, Grotzfeld R, Berst F, Marzinzik A, Cowan-Jacob SW, Furet P, Mestan J. Inhibitors of 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, Sim T, 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 allosteric with 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. Oligomerization inhibition, combined with allosteric inhibition, abrogates the transformation potential of T315I-positive BCR/ABL. Leukemia. 2009 Dec;23(12):2242-7. doi: 10.1038/leu.2009.194. Epub 2009 Oct 1. PubMed PMID: 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 kinase localizes to the endoplasmic reticulum upon binding to an allosteric inhibitor. J Biol Chem. 2009 Oct 16;284(42):29005-14. doi: 10.1074/jbc.M109.026633. Epub 2009 Aug 13. PubMed PMID: 19679652; PubMed Central PMCID: PMC2781447.

19: Ohren JF, Sebolt-Leopold JS. Inhibitors of Bcr-abl... breaking new ground 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, Hur W, Ding S, Manley P, Mestan J, Fabbro D, Gray NS. Allosteric inhibitors of Bcr-abl-dependent cell proliferation. Nat Chem Biol. 2006 Feb;2(2):95-102. Epub 2006 Jan 15. PubMed PMID: 16415863.