GNF-5

Names

[ Name ]:
GNF-5

[Synonym ]:
Benzamide,N-(2-hydroxyethyl)-3-(6-((4-(trifluoromethoxy)phenyl)amino)-4-pyrimidinyl)
QC-4300
Benzamide, N-(2-hydroxyethyl)-3-[6-[[4-(trifluoromethoxy)phenyl]amino]-4-pyrimidinyl]-
N-(2-hydroxyethyl)-3-(6-(4-(trifluoromethoxy)phenylamino)pyrimidin-4-yl)benzamide
GNF-5
N-(2-Hydroxyethyl)-3-(6-{[4-(trifluoromethoxy)phenyl]amino}-4-pyrimidinyl)benzamide
UNII-3ZUA56XMQQ

Biological Activity

[Description]:

GNF-5, an analogue of GNF-2 with improved pharmacokinetic properties, is a selective non-ATP competitive inhibitor of Bcr-Abl with an IC50 value of 0.22±0.1 uM (Wild type Abl).IC50 Value: 0.22±0.1 uM (Wild type Abl) [1]Target: Abl GNF-5 is a cell-permeable GNF-2 N-hydroxyethyl carboxamide analog that exhibits in vivo efficacy in suppressing the proliferation of Bcr-abl-expressing Ba/F3 (93% and 83% of no-treatment control, respectively, on days 5 and 7 post treatment; 100 mg/kg b.i.d.) and bone marrow cells (~75% of no-treatment control in both WBC counts and spleen weight on day 7 post treatment; 50 mg/kg b.i.d.) in murine xenograft models of leukemia. Similar to GNF-2, GNF-5 exerts its effect via an allosteric mechanism (IC50 = 0.22 M against wild-type Abl) by targeting the myristate-binding pocket near the c-terminus of Abl kinase domain and thereby altering the conformational dynamics of the ATP-binding pocket. GNF-5 is ineffective toward the myristate-binding site mutant E505K and the ATP-binding site 'gatekeeper' mutant T315I.

[Related Catalog]:

Signaling Pathways >> Protein Tyrosine Kinase/RTK >> Bcr-Abl

Research Areas >> Cancer

[References]

[1]. Zhang J, et al. Targeting Bcr-Abl by combining allosteric with ATP-binding-site inhibitors. Nature. 2010 Jan 28;463(7280):501-6.

[2]. Meirson T, et al. Targeting invadopodia-mediated breast cancer metastasis by using ABL kinase inhibitors. Oncotarget. 2018 Apr 24;9(31):22158-22183.

[Related Small Molecules]

Nocodazole | Asciminib | Degrasyn(WP1130) | Bafetinib (INNO-406) | DCC-2036 (Rebastinib) | KW-2449 | AST 487 | PD173955 | XL228 | DPH | GNF-2 | GNF-7 | GZD824 | Flumatinib | Radotinib

Chemical & Physical Properties

[ Density]:
1.4±0.1 g/cm3

[ Boiling Point ]:
612.4±55.0 °C at 760 mmHg

[ Molecular Formula ]:
C₂₀H₁₇F₃N₄O₃

[ Molecular Weight ]:
418.369

[ Flash Point ]:
324.2±31.5 °C

[ Exact Mass ]:
418.125275

[ PSA ]:
99.86000

[ LogP ]:
3.31

[ Appearance of Characters ]:
white to beige

[ Vapour Pressure ]:
0.0±1.9 mmHg at 25°C

[ Index of Refraction ]:
1.600

[ Storage condition ]:
2-8°C

[ Water Solubility ]:
DMSO: soluble10mg/mL (clear solution)

MSDS

Click to get detail MSDS

Safety Information

[ Symbol ]:

GHS06

[ Signal Word ]:
Danger

[ Hazard Statements ]:
H301-H319

[ Precautionary Statements ]:
P301 + P310-P305 + P351 + P338

[ Hazard Codes ]:
T

[ Risk Phrases ]:
25-36

[ Safety Phrases ]:
22-45

[ RIDADR ]:
UN 2811 6.1 / PGIII

[ HS Code ]:
2933599090

Synthetic Route

Click to get detail synthetic route

Precursor & DownStream

Precursor

DownStream

Customs

[ HS Code ]: 2933599090

[ Summary ]:
2933599090. other compounds containing a pyrimidine ring (whether or not hydrogenated) or piperazine ring in the structure. VAT:17.0%. Tax rebate rate:13.0%. . MFN tariff:6.5%. General tariff:20.0%