CAS 778270-11-4|GNF-2

Introduction：Basic information about CAS 778270-11-4|GNF-2, including its chemical name, molecular formula, synonyms, physicochemical properties, and safety information, etc.

Table of Contents

1. Names
2. GNF-2 BiologicalActivity
3. Chemical & Physical Properties
4. Safety Information
5. Articles2
6. Synonyms

Common Name	GNF-2
CAS Number	778270-11-4	Molecular Weight	374.317
Density	1.4±0.1 g/cm3	Boiling Point	536.4±50.0 °C at 760 mmHg
Molecular Formula	C₁₈H₁₃F₃N₄O₂	Melting Point	/
MSDS	ChineseUSA	Flash Point	278.2±30.1 °C
Symbol	GHS07	Signal Word	Warning

Names

Name	3-[6-[4-(trifluoromethoxy)anilino]pyrimidin-4-yl]benzamide
Synonym	More Synonyms

GNF-2 BiologicalActivity

Description	GNF-2 is a highly selective non-ATP competitive inhibitor of oncogenic Bcr-Abl activity (IC50 = 0.14 μM).IC50 value: 0.14 uM [1]Target: Bcr-Ablin vitro: Ba/F3 cells harboring native or T315I mutated Bcr-Abl constructs were treated with GNF-2 and AKIs. We monitored the effect of GNF-2 with AKIs on the proliferation and clonigenicity of the different Ba/F3 cells. In addition, we monitored the auto-phosphorylation activity of Bcr-Abl and JAK2 in cells treated with GNF-2 and AKIs [2]. GNF-2 increased the effects of AKIs on unmutated BCR/ABL. Interestingly, the combination of Dasatinib and GNF-2 overcame resistance of BCR/ABL-T315I in all models used in a synergistic manner [3].GNF-2 dose-dependently inhibited the proliferation of osteoclast precursors through the suppression of the M-CSFR c-Fms. In addition, GNF-2 accelerated osteoclast apoptosis by inducing caspase-3 and Bim expression. Furthermore, GNF-2 interfered with actin cytoskeletal organization and subsequently blocked the bone-resorbing activity of mature osteoclasts [4].in vivo: Combining PDMP and GNF-2 eliminated transplanted-CML-T315I-mutants in vivo and dose dependently sensitized primary cells from CML T315I patients to GNF-2-induced proliferation inhibition and apoptosis[5].
Related Catalog	Signaling Pathways >>Protein Tyrosine Kinase/RTK >>Bcr-AblResearch Areas >>Cancer
References	[1]. Adrián FJ, et al. Allosteric inhibitors of Bcr-abl-dependent cell proliferation. Nat Chem Biol. 2006 Feb;2(2):95-102. [2]. Khateb M, et al. 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. [3]. Mian AA, et al. 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. [4]. Kim HJ, et al. The tyrosine kinase inhibitor GNF-2 suppresses osteoclast formation and activity. J Leukoc Biol. 2013 Oct 15. [5]. Huang WC, et al. 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.

Description

GNF-2 is a highly selective non-ATP competitive inhibitor of oncogenic Bcr-Abl activity (IC50 = 0.14 μM).IC50 value: 0.14 uM [1]Target: Bcr-Ablin vitro: Ba/F3 cells harboring native or T315I mutated Bcr-Abl constructs were treated with GNF-2 and AKIs. We monitored the effect of GNF-2 with AKIs on the proliferation and clonigenicity of the different Ba/F3 cells. In addition, we monitored the auto-phosphorylation activity of Bcr-Abl and JAK2 in cells treated with GNF-2 and AKIs [2]. GNF-2 increased the effects of AKIs on unmutated BCR/ABL. Interestingly, the combination of Dasatinib and GNF-2 overcame resistance of BCR/ABL-T315I in all models used in a synergistic manner [3].GNF-2 dose-dependently inhibited the proliferation of osteoclast precursors through the suppression of the M-CSFR c-Fms. In addition, GNF-2 accelerated osteoclast apoptosis by inducing caspase-3 and Bim expression. Furthermore, GNF-2 interfered with actin cytoskeletal organization and subsequently blocked the bone-resorbing activity of mature osteoclasts [4].in vivo: Combining PDMP and GNF-2 eliminated transplanted-CML-T315I-mutants in vivo and dose dependently sensitized primary cells from CML T315I patients to GNF-2-induced proliferation inhibition and apoptosis[5].

Related Catalog

Signaling Pathways >>Protein Tyrosine Kinase/RTK >>Bcr-AblResearch Areas >>Cancer

References

[1]. Adrián FJ, et al. Allosteric inhibitors of Bcr-abl-dependent cell proliferation. Nat Chem Biol. 2006 Feb;2(2):95-102.

[2]. Khateb M, et al. 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.

[3]. Mian AA, et al. 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.

[4]. Kim HJ, et al. The tyrosine kinase inhibitor GNF-2 suppresses osteoclast formation and activity. J Leukoc Biol. 2013 Oct 15.

[5]. Huang WC, et al. 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.

Chemical & Physical Properties

Density	1.4±0.1 g/cm3
Boiling Point	536.4±50.0 °C at 760 mmHg
Molecular Formula	C₁₈H₁₃F₃N₄O₂
Molecular Weight	374.317
Flash Point	278.2±30.1 °C
Exact Mass	374.099060
PSA	90.13000
LogP	3.68
Appearance of Characters	off-white
Vapour Pressure	0.0±1.4 mmHg at 25°C
Index of Refraction	1.611
InChIKey	WEVYNIUIFUYDGI-UHFFFAOYSA-N
SMILES	NC(=O)c1cccc(-c2cc(Nc3ccc(OC(F)(F)F)cc3)ncn2)c1
Storage condition	2-8°C
Water Solubility	H2O: <2mg/mL

Safety Information

Symbol	GHS07
Signal Word	Warning
Hazard Statements	H315-H319-H335
Precautionary Statements	P261-P305 + P351 + P338
Personal Protective Equipment	dust mask type N95 (US);Eyeshields;Gloves
Hazard Codes	Xi
Risk Phrases	36/37/38
Safety Phrases	26
RIDADR	NONH for all modes of transport

Articles2

Allosteric inhibitors of Bcr-abl-dependent cell proliferation.

Nat. Chem. Biol. 2 , 95-102, (2006)

Chronic myelogenous leukemia (CML) is a myeloproliferative disorder characterized at the molecular level by the expression of Bcr-abl, a 210-kDa fusion protein with deregulated tyrosine kinase activit...

Inhibitors of Bcr-abl... breaking new ground again.

Nat. Chem. Biol. 2nd ed.,, 63-64, (2006)

Synonyms

Benzamide, 3-[6-[[4-(trifluoromethoxy)phenyl]amino]-4-pyrimidinyl]-

3k5v

3-(6-{[4-(Trifluoromethoxy)phenyl]amino}-4-pyrimidinyl)benzamide

GNF-2

Bcr-abl Inhibitor

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