Synonym
JNJ-38877605; JNJ38877605; JNJ 38877605.
IUPAC/Chemical Name
6-(difluoro(6-(1-methyl-1H-pyrazol-3-yl)-[1,2,4]triazolo[4,3-b]pyridazin-3-yl)methyl)quinoline
InChi Key
HUWHDIWESZXGII-UHFFFAOYSA-N
InChi Code
InChI=1S/C19H13F2N7/c1-27-10-8-16(25-27)15-6-7-17-23-24-18(28(17)26-15)19(20,21)13-4-5-14-12(11-13)3-2-9-22-14/h2-11H,1H3
SMILES Code
CN1N=C(C2=NN3C(C=C2)=NN=C3C(C4=CC=C5N=CC=CC5=C4)(F)F)C=C1
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 soluble in water.
Shelf Life
>5 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
JNJ-38877605 is a small-molecule, ATP-competitive inhibitor of the catalytic activity of c-Met. JNJ-38877605 showed ~600-fold selectivity for c-Met compared with a panel of 250 diverse tyrosine and serine-threonine kinases and was found to potently inhibit HGF-stimulated and constitutively activated c-Met phosphorylation in vitro. (source: Clin Cancer Res April 1, 2009 15; 2207 ).
Biological target:
JNJ-38877605 is an ATP-competitive inhibitor of c-Met with IC50 of 4 nM, 600-fold selective for c-Met than 200 other tyrosine and serine-threonine kinases.
In vitro activity:
To investigate the effect of different concentrations of inhibitor JNJ-38877605 on PC-3 cells with CCK-8 assay, PC-3 cells were incubated with different concentrations (0.125 nM, 0.5 nM, 1 nM, 2.5 nM, 5 nM, 10 nM) of JNJ-38877605 for 48 h at 37°C. The proliferation of PC-3 cells was examined by CCK-8. Different concentrations of JNJ-38877605 did not inhibit PC-3 cell proliferation after 48 h.
Reference: Int J Clin Exp Med. 2015 Apr 15;8(4):6563-7. https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/26131286/
In vivo activity:
To study their ability to metastasize to bone, renal CSCs were injected in NOD/SCID mice implanted with a human bone and the effect of a c-MET inhibitor (JNJ-38877605) was tested on bone metastasis development. JNJ-38877605 inhibited the formation of metastases at bone implant site. It was shown that JNJ-38877605 inhibited the activation of osteoclasts induced by RCC stem cells and it stimulated osteoblast activity, finally resulting in a reduction of bone turnover consistent with the inhibition of bone metastases. The circulating levels of osteotropic factors induced by RCC stem cells in the sera of mice treated with c-Met inhibitor was measured, showing that IL-11 and CCL20 were reduced in mice treated with JNJ-38877605, strongly supporting the involvement of c-MET in the regulation of this process.
Reference: Oncotarget. 2016 Jul 19;7(29):45525-45537. https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/27322553/
|
Solvent |
mg/mL |
mM |
| Solubility |
| DMSO |
30.0 |
79.50 |
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
377.35
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. Li W, Wang Z, Wang L, He X, Wang G, Liu H, Guo F, Wang Z, Chen G. Effectiveness of inhibitor rapamycin, saracatinib, linsitinib and JNJ-38877605 against human prostate cancer cells. Int J Clin Exp Med. 2015 Apr 15;8(4):6563-7. PMID: 26131286; PMCID: PMC4483836.
In vivo protocol:
1. D'Amico L, Belisario D, Migliardi G, Grange C, Bussolati B, D'Amelio P, Perera T, Dalmasso E, Dalle Carbonare L, Godio L, Comoglio P, Trusolino L, Ferracini R, Roato I. C-met inhibition blocks bone metastasis development induced by renal cancer stem cells. Oncotarget. 2016 Jul 19;7(29):45525-45537. doi: 10.18632/oncotarget.9997. PMID: 27322553; PMCID: PMC5216739.
1: De Bacco F, Luraghi P, Medico E, Reato G, Girolami F, Perera T, Gabriele P, Comoglio PM, Boccaccio C. Induction of MET by ionizing radiation and its role in radioresistance and invasive growth of cancer. J Natl Cancer Inst. 2011 Apr 20;103(8):645-61. Epub 2011 Apr 4. PubMed PMID: 21464397.
2: Galimi F, Torti D, Sassi F, Isella C, Corà D, Gastaldi S, Ribero D, Muratore A, Massucco P, Siatis D, Paraluppi G, Gonella F, Maione F, Pisacane A, David E, Torchio B, Risio M, Salizzoni M, Capussotti L, Perera T, Medico E, Di Renzo MF, Comoglio PM, Trusolino L, Bertotti A. Genetic and expression analysis of MET, MACC1, and HGF in metastatic colorectal cancer: response to met inhibition in patient xenografts and pathologic correlations. Clin Cancer Res. 2011 May 15;17(10):3146-56. Epub 2011 Mar 29. PubMed PMID: 21447729.
3: Benvenuti S, Lazzari L, Arnesano A, Li Chiavi G, Gentile A, Comoglio PM. Ron kinase transphosphorylation sustains MET oncogene addiction. Cancer Res. 2011 Mar 1;71(5):1945-55. Epub 2011 Jan 6. PubMed PMID: 21212418.
