GNF-5 | CAS#778277-15-9 | Bcr-Abl inhibitor

MedKoo Cat#: 407206 | Name: GNF-5

Description:

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

GNF-5 is a selective allosteric inhibitor of Bcr-Abl (IC50 = 220 nM for wild-type Abl). GNF-5 has improved pharmacokinetic properties, when used in combination with the ATP-competitive inhibitors imatinib or nilotinib, suppressed the emergence of resistance mutations in vitro, displayed additive inhibitory activity in biochemical and cellular assays against T315I mutant human Bcr-Abl and displayed in vivo efficacy against this recalcitrant mutant in a murine bone-marrow transplantation model.

Chemical Structure

GNF-5

CAS#778277-15-9

Theoretical Analysis

MedKoo Cat#: 407206

Name: GNF-5

CAS#: 778277-15-9

Chemical Formula: C20H17F3N4O3

Exact Mass: 418.1253

Molecular Weight: 418.38

Elemental Analysis: C, 57.42; H, 4.10; F, 13.62; N, 13.39; O, 11.47

Price and Availability

Size	Price	Availability
10mg	USD 110.00	Ready to ship
25mg	USD 220.00	Ready to ship
50mg	USD 385.00	Ready to ship
100mg	USD 685.00	Ready to ship
200mg	USD 1,250.00	Ready to ship
500mg	USD 2,650.00	Ready to ship
1g	USD 4,250.00	2 weeks
2g	USD 6,650.00	2 weeks

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Related CAS #

No Data

Synonym

GNF-5; GNF 5; GNF5.

IUPAC/Chemical Name

N-(2-Hydroxyethyl)-3-[6-[[4-(trifluoromethoxy)phenyl]amino]-4-pyrimidinyl]benzamide

InChi Key

IIQUYGWWHIHOCF-UHFFFAOYSA-N

InChi Code

InChI=1S/C20H17F3N4O3/c21-20(22,23)30-16-6-4-15(5-7-16)27-18-11-17(25-12-26-18)13-2-1-3-14(10-13)19(29)24-8-9-28/h1-7,10-12,28H,8-9H2,(H,24,29)(H,25,26,27)

SMILES Code

O=C(NCCO)C1=CC=CC(C2=NC=NC(NC3=CC=C(OC(F)(F)F)C=C3)=C2)=C1

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).

HS Tariff Code

2934.99.9001

More Info

Product Data

Product Data

Certificate of Analysis

View CoA: current batch, Lot#A9T09K23

QC Data

View QC data: current batch, Lot#A9T09K23

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

Biological target:

GNF-5 is a Bcr-Abl inhibitor with an IC50 of 220 nM.

In vitro activity:

To investigate the growth of SK-HEP1 (human hepatocarcninoma) cells following treatment with imatinib, GNF5 and GNF2, the change in the morphology, proliferation and colony formation of SK-HEP1 cells for 24, 48, and 72 hours was examined. Figure 2A shows that all drugs at 20 μM time-dependently inhibited the proliferation of SK-HEP1 cells. Particularly, imatinib and GNF5 significantly decreased cell viability by more than 50% at 72 hours, which was confirmed by the cell morphology images (Fig. 2B). Additionlly, the colony formation assay showed that all compound-treated cells formed fewer colonies compared to the control group (Fig. 2B). Collectively, these results demonstrate that imatinib and GNF5 significantly inhibited the growth of SK-HEP1 cells, compared to the same concentration of GNF2. Reference: J Cancer Prev. 2018 Dec;23(4):170-175. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6330986/

In vivo activity:

TBD

	Solvent	mg/mL	mM
Solubility
	DMSO	46.0	109.85
	Ethanol	10.1	24.21
	DMF	25.0	59.75
	DMF:PBS (pH 7.2) (1:2)	0.3	0.60

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 418.38 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Concentration / Solvent Volume / Mass	1 mg	5 mg	10 mg
1 mM	1.15 mL	5.76 mL	11.51 mL
5 mM	0.23 mL	1.15 mL	2.3 mL
10 mM	0.12 mL	0.58 mL	1.15 mL
50 mM	0.02 mL	0.12 mL	0.23 mL

Formulation protocol:

1. Kim SH, Kim MO, Kim KR. Anti-growth Effects of Imatinib and GNF5 via Regulation of Skp2 in Human Hepatocellular Carcinoma Cells. J Cancer Prev. 2018 Dec;23(4):170-175. doi: 10.15430/JCP.2018.23.4.170. Epub 2018 Dec 30. Erratum in: J Cancer Prev. 2019 Mar;24(1):63. PMID: 30671399; PMCID: PMC6330986.

In vitro protocol:

In vivo protocol:

TBD

1: Skora L, Kempf D, Mestan J, D'Orazio D, Jahnke W. Phosphorylation of Tyr245 in the open-inhibited state of Abelson kinase does not induce downstream signaling. Eur J Haematol. 2015 Jul 7. doi: 10.1111/ejh.12627. [Epub ahead of print] PubMed PMID: 26154982. 2: Karunakaran U, Park SJ, Jun do Y, Sim T, Park KG, Kim MO, Lee IK. Non-receptor tyrosine kinase inhibitors enhances β-cell survival by suppressing the PKCδ signal transduction pathway in streptozotocin-induced β-cell apoptosis. Cell Signal. 2015 Jun;27(6):1066-74. doi: 10.1016/j.cellsig.2015.01.018. Epub 2015 Feb 12. PubMed PMID: 25683919. 3: Chen S, Tang DD. c-Abl tyrosine kinase regulates cytokinesis of human airway smooth muscle cells. Am J Respir Cell Mol Biol. 2014 Jun;50(6):1076-83. doi: 10.1165/rcmb.2013-0438OC. PubMed PMID: 24392933; PubMed Central PMCID: PMC4068917. 4: Skora L, Mestan J, Fabbro D, Jahnke W, Grzesiek S. NMR reveals the allosteric opening and closing of Abelson tyrosine kinase by ATP-site and myristoyl pocket inhibitors. Proc Natl Acad Sci U S A. 2013 Nov 19;110(47):E4437-45. doi: 10.1073/pnas.1314712110. Epub 2013 Nov 4. PubMed PMID: 24191057; PubMed Central PMCID: PMC3839726. 5: Cleary RA, Wang R, Wang T, Tang DD. Role of Abl in airway hyperresponsiveness and airway remodeling. Respir Res. 2013 Oct 11;14:105. doi: 10.1186/1465-9921-14-105. PubMed PMID: 24112389; PubMed Central PMCID: PMC3852349. 6: Iacob RE, Zhang J, Gray NS, Engen JR. Allosteric interactions between the myristate- and ATP-site of the Abl kinase. PLoS One. 2011 Jan 10;6(1):e15929. doi: 10.1371/journal.pone.0015929. PubMed PMID: 21264348; PubMed Central PMCID: PMC3018526. 7: 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. 8: 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. 9: 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.

Description:

Chemical Structure

Theoretical Analysis

Price and Availability

Preparing Stock Solutions

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