Synonym
GNF5837; GNF-5837; GNF 5837.
IUPAC/Chemical Name
(Z)-1-(3-((3-((1H-pyrrol-2-yl)methylene)-2-oxoindolin-6-yl)amino)-4-methylphenyl)-3-(2-fluoro-5-(trifluoromethyl)phenyl)urea
InChi Key
YYDUWLSETXNJJT-MTJSOVHGSA-N
InChi Code
InChI=1S/C28H21F4N5O2/c1-15-4-6-19(35-27(39)37-25-11-16(28(30,31)32)5-9-22(25)29)13-23(15)34-18-7-8-20-21(12-17-3-2-10-33-17)26(38)36-24(20)14-18/h2-14,33-34H,1H3,(H,36,38)(H2,35,37,39)/b21-12-
SMILES Code
O=C(NC1=CC(C(F)(F)F)=CC=C1F)NC2=CC=C(C)C(NC3=CC(NC/4=O)=C(C=C3)C4=C\C5=CC=CN5)=C2
Appearance
Orange to red 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-5837 is a potent, selective, and orally bioavailable pan-tropomyosin receptor kinase (TRK) inhibitor which display antiproliferative effects in cellular Ba/F3 assays ( IC50 values of 7 nM, 9 nM and 11 nM for cells containing the fusion proteins Tel-TrkC, Tel-TrkB and Tel-TrkA, respectively).
In vitro activity:
GNF‑5837, an inhibitor of TrkA and TrkB, suppressed the cell viability of renal carcinoma 786O and Caki‑2 cells in a concentration‑dependent manner. GNF‑5837 treatment led to decreased activities of TrkA and TrkB signaling, accompanied by reduced phosphorylation levels of AKT and extracellular signal‑regulated kinase (ERK) kinases, which was detected by western blot assay. GNF‑5837 induced G0/G1‑phase arrest and apoptosis. Consistently, GNF‑5837 affected the expression of p21, c‑Myc, and survivin proteins. Meanwhile, a wound healing assay showed that GNF‑5837 inhibited the migration ability of RCC cells by impairing Rac1 activity. GNF‑5837 also enhanced the cytotoxic effects of sunitinib via inhibition of ERK kinase.
Reference: Oncol Rep. 2019 Nov;42(5):2039-2048. https://www.spandidos-publications.com/or/42/5/2039
In vivo activity:
To determine the in vivo PK data, GNF-5837 (compound 22) was administered intravenously to male Balb/c mice and Sprague–Dawley rats, and the drug clearance was found to be low and the volume of distribution moderate (mice) to high (rat). When administered orally by gavage, it gave moderate biovailability in both mice and rats due to poor absorption deriving from a combination of poor permeability and low aqueous solubility (Table 3). In the mice, the drug concentration in the brain after oral delivery was below the limit of quantitation, suggesting that the compound does not effectively cross the blood–brain barrier. To demonstrate in vivo efficacy, compound 22 was administered at ascending doses once daily for 10 days in mice (Figure 2) with established tumor xenografts derived from RIE cells expressing both TRKA and NGF. In this study, 72 and 100% tumor regression was observed at 50 and 100 mg/kg, respectively. At 25 mg/kg, only partial tumor growth inhibition was achieved.
Reference: ACS Med Chem Lett. 2012 Jan 1;3(2):140-5. https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24900443/
|
Solvent |
mg/mL |
mM |
| Solubility |
| DMSO |
32.0 |
59.76 |
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
535.49
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 |
In vitro protocol:
1. Chen Y, Wang H, Chen Y, Wang M, Ding G, Li T. Trk inhibitor GNF‑5837 suppresses the tumor growth, survival and migration of renal cell carcinoma. Oncol Rep. 2019 Nov;42(5):2039-2048. doi: 10.3892/or.2019.7296. Epub 2019 Aug 28. PMID: 31485624.
2. Aristizabal Prada ET, Heinzle V, Knösel T, Nölting S, Spöttl G, Maurer J, Spitzweg C, Angele M, Schmidt N, Beuschlein F, Stalla GK, Blaser R, Kuhn KA, Auernhammer CJ. Tropomyosin receptor kinase: a novel target in screened neuroendocrine tumors. Endocr Relat Cancer. 2018 May;25(5):547-560. doi: 10.1530/ERC-17-0201. Epub 2018 Mar 21. PMID: 29563190.
In vivo protocol:
1. Albaugh P, Fan Y, Mi Y, Sun F, Adrian F, Li N, Jia Y, Sarkisova Y, Kreusch A, Hood T, Lu M, Liu G, Huang S, Liu Z, Loren J, Tuntland T, Karanewsky DS, Seidel HM, Molteni V. Discovery of GNF-5837, a Selective TRK Inhibitor with Efficacy in Rodent Cancer Tumor Models. ACS Med Chem Lett. 2012 Jan 1;3(2):140-5. doi: 10.1021/ml200261d. PMID: 24900443; PMCID: PMC4025649.
Pam Albaugh , Yi Fan , Yuan Mi , Fangxian Sun , Francisco Adrian , Nanxin Li , Yong Jia , Yelena Sarkisova , Andreas Kreusch , Tami Hood , Min Lu , Guoxun Liu , Shenlin Huang , Zuosheng Liu , Jon Loren , Tove Tuntland , Donald S. Karanewsky , H. Martin Seidel , and Valentina Molteni. Discovery of GNF-5837, a Selective TRK Inhibitor with Efficacy in Rodent Cancer Tumor Models. ACS Med. Chem. Lett., 2012, 3 (2), pp 140–145.
