WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 407257
CAS#: 839706-07-9
Description: GNF-7 is a type-II T315I inhibitor. GNF-7 inhibits Ack1 and germinal center kinase (GCK). GNF-7 displayed significant in vivo efficacy against T315I-Bcr-Abl without appreciable toxicity in a bioluminescent xenograft mouse model using a transformed T315I-Bcr-Abl-Ba/F3 cell line that has a stable luciferase expression. GNF-7 is among the first type-II inhibitors capable of inhibiting T315I to be described and will serve as a valuable lead to design the third generation Bcr-Abl kinase inhibitors.
MedKoo Cat#: 407257
Name: GNF-7
CAS#: 839706-07-9
Chemical Formula: C28H24F3N7O2
Exact Mass: 547.1944
Molecular Weight: 547.5422
Elemental Analysis: C, 61.42; H, 4.42; F, 10.41; N, 17.91; O, 5.84
Synonym: GNF-7; GNF7; GNF 7.
IUPAC/Chemical Name: N-(4-methyl-3-(1-methyl-7-((6-methylpyridin-3-yl)amino)-2-oxo-1,4-dihydropyrimido[4,5-d]pyrimidin-3(2H)-yl)phenyl)-3-(trifluoromethyl)benzamide
InChi Key: SZNYUUZOQHNEKB-UHFFFAOYSA-N
InChi Code: InChI=1S/C28H24F3N7O2/c1-16-7-9-21(34-25(39)18-5-4-6-20(11-18)28(29,30)31)12-23(16)38-15-19-13-33-26(36-24(19)37(3)27(38)40)35-22-10-8-17(2)32-14-22/h4-14H,15H2,1-3H3,(H,34,39)(H,33,35,36)
SMILES Code: O=C(NC1=CC=C(C)C(N2CC3=CN=C(NC4=CC=C(C)N=C4)N=C3N(C)C2=O)=C1)C5=CC=CC(C(F)(F)F)=C5
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
| Biological target: | GNF-7 is a Bcr-Abl inhibitor, with IC50s of 133 nM and 61 nM for Bcr-AblWT and Bcr-AblT315I, respectively. GNF-7 also possesses inhibitory activity against both ACK1 (activated CDC42 kinase 1) and GCK (germinal center kinase) with IC50s of 25 nM and 8 nM, respectively. |
| In vitro activity: | GNF-7 effectively suppressed proliferation of cancer cells harboring mtRAS with submicromolar potencies (GI50s = 0.169 to 0.938 µM). Reference: Front Oncol. 2021 Dec 9;11:768022. https://pubmed.ncbi.nlm.nih.gov/34956887/ |
| In vivo activity: | TBD |
| Solvent | Max Conc. mg/mL | Max Conc. mM | |
|---|---|---|---|
| Solubility | |||
| DMF | 10.0 | 18.26 | |
| DMF:PBS (pH 7.2) (1:2) | 0.3 | 0.55 | |
| DMSO | 20.6 | 37.61 | |
| Ethanol | 0.1 | 0.18 |
The following data is based on the product molecular weight 547.5422 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 N, Shin I, Kim Y, Jeon E, Lee J, Lee C, Nam Y, Lee S, Ju E, Kim C, Son W, Ryu S, Ko M, Sim T. Novel Small Molecules Capable of Blocking mtRAS-Signaling Pathway. Front Oncol. 2021 Dec 9;11:768022. doi: 10.3389/fonc.2021.768022. PMID: 34956887; PMCID: PMC8695447. |
| In vitro protocol: | 1. Kim N, Shin I, Kim Y, Jeon E, Lee J, Lee C, Nam Y, Lee S, Ju E, Kim C, Son W, Ryu S, Ko M, Sim T. Novel Small Molecules Capable of Blocking mtRAS-Signaling Pathway. Front Oncol. 2021 Dec 9;11:768022. doi: 10.3389/fonc.2021.768022. PMID: 34956887; PMCID: PMC8695447. |
| In vivo protocol: | TBD |
1: Liang X, Liu X, Wang B, Zou F, Wang A, Qi S, Chen C, Zhao Z, Wang W, Qi Z, Lv
F, Hu Z, Wang L, Zhang S, Liu Q, Liu J. Discovery of
2-((3-amino-4-methylphenyl)amino)-N-(2-methyl-5-(3-(trifluoromethyl)benzamido)phe
nyl)-4-(methylamino)pyrimidine-5-carboxamide (CHMFL-ABL-053) as a potent,
selective and orally available BCR-ABL/SRC/p38 kinase inhibitor for Chronic
Myeloid Leukemia. J Med Chem. 2016 Jan 20. [Epub ahead of print] PubMed PMID:
26789553.
2: Lu X, Zhang Z, Ren X, Pan X, Wang D, Zhuang X, Luo J, Yu R, Ding K. Hybrid
pyrimidine alkynyls inhibit the clinically resistance related Bcr-Abl(T315I)
mutant. Bioorg Med Chem Lett. 2015 Sep 1;25(17):3458-63. doi:
10.1016/j.bmcl.2015.07.006. Epub 2015 Jul 9. PubMed PMID: 26195136.
3: Nonami A, Sattler M, Weisberg E, Liu Q, Zhang J, Patricelli MP, Christie AL,
Saur AM, Kohl NE, Kung AL, Yoon H, Sim T, Gray NS, Griffin JD. Identification of
novel therapeutic targets in acute leukemias with NRAS mutations using a
pharmacologic approach. Blood. 2015 May 14;125(20):3133-43. doi:
10.1182/blood-2014-12-615906. Epub 2015 Apr 1. PubMed PMID: 25833960; PubMed
Central PMCID: PMC4432008.
4: Choi HG, Ren P, Adrian F, Sun F, Lee HS, Wang X, Ding Q, Zhang G, Xie Y, Zhang
J, Liu Y, Tuntland T, Warmuth M, Manley PW, Mestan J, Gray NS, Sim T. A type-II
kinase inhibitor capable of inhibiting the T315I "gatekeeper" mutant of Bcr-Abl.
J Med Chem. 2010 Aug 12;53(15):5439-48. doi: 10.1021/jm901808w. PubMed PMID:
20604564; PubMed Central PMCID: PMC4134510.
