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Chemical Structure| 943540-75-8 Chemical Structure| 943540-75-8

Structure of JNJ-38877605
CAS No.: 943540-75-8

Chemical Structure| 943540-75-8

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JNJ-38877605 is an ATP-competitive inhibitor of c-Met with IC50 of 4 nM.

4.5 *For Research Use Only !

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Product Details of JNJ-38877605

CAS No. :943540-75-8
Formula : C19H13F2N7
M.W : 377.35
SMILES Code : CN1N=CC(C2=NN3C(C=C2)=NN=C3C(C4=CC=C5N=CC=CC5=C4)(F)F)=C1
MDL No. :MFCD11977274
InChI Key :JRWCBEOAFGHNNU-UHFFFAOYSA-N
Pubchem ID :46911863

Safety of JNJ-38877605

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H317-H319
Precautionary Statements:P280-P305+P351+P338

Related Pathways of JNJ-38877605

RTK

Isoform Comparison

Biological Activity

In Vitro:

Cell Line
Concentration Treated Time Description References
MHCC97L 10-100 nM 4 hours Inhibition of p-MET and its downstream pathways PMC4603939
Huh7 10-100 nM 4 hours Inhibition of HGF-induced p-MET and its downstream pathways PMC4603939
3T3-L1 cells 20 µM 8 days JNJ-38877605 inhibits c-Met phosphorylation, reduces lipid accumulation and triglyceride content, without affecting cell viability. PMC10179087
MHCC97L 315 ± 26.3 nM 72 hours To evaluate the anti-proliferative effect of Tivantinib on HCC cells, results showed that Tivantinib inhibited both MET-dependent and independent HCC cells. PMC4603939
MHCC97H 368 ± 45.4 nM 72 hours To evaluate the anti-proliferative effect of Tivantinib on HCC cells, results showed that Tivantinib inhibited both MET-dependent and independent HCC cells. PMC4603939
Huh7 265 ± 18.7 nM 72 hours To evaluate the anti-proliferative effect of Tivantinib on HCC cells, results showed that Tivantinib inhibited both MET-dependent and independent HCC cells. PMC4603939
HepG2 392 ± 48.7 nM 72 hours To evaluate the anti-proliferative effect of Tivantinib on HCC cells, results showed that Tivantinib inhibited both MET-dependent and independent HCC cells. PMC4603939

In Vivo:

Species
Animal Model
Administration Dosage Frequency Description References
rabbits renal toxicity model oral 75 mg/kg Three times a week, continuous treatment to evaluate the renal toxicity of JNJ-38877605 in rabbits, showing renal crystal formation with degenerative and inflammatory changes PMC4433755
BALB/c nude mice MHCC97L xenograft model Oral 10 nM Single administration To evaluate the effect of JNJ-38877605 on inhibition of MET expression in vivo PMC4603939
Mice RU-P melanoma cell tumor xenografts Oral 200, 300, 350 mg/kg/week 1 month To study the therapeutic efficacy of JNJ-38877605 in vivo, results showed that JNJ-38877605 significantly reduced tumor size, decreased p-c-Met expression, and reduced blood vessel formation. PMC4128856
BALB/c nude mice MHCC97L xenograft model Oral 0.9 g/L Daily, until the end of the experiment To evaluate the anti-tumor effect of Tivantinib in vivo, results showed that Tivantinib significantly inhibited tumor growth and exhibited anti-proliferative and pro-apoptotic effects. PMC4603939

Clinical Trial:

NCT Number Conditions Phases Recruitment Completion Date Locations
NCT00651365 Neoplasms PHASE1 TERMINATED 2025-12-10 -

Protocol

Bio Calculators
Preparing Stock Solutions 1mg 5mg 10mg

1 mM

5 mM

10 mM

2.65mL

0.53mL

0.27mL

13.25mL

2.65mL

1.33mL

26.50mL

5.30mL

2.65mL

Dissolving Methods
Please choose the appropriate dissolution scheme according to your animal administration guide.For the following dissolution schemes, clear stock solution should be prepared according to in vitro experiments, and then cosolvent should be added in turn:

in order to ensure the reliability of the experimental results, the clarified stock solution can be properly preserved according to the storage conditions; The working fluid for in vivo experiment is recommended to be prepared now and used on the same day;

The percentage shown in front of the following solvent refers to the volume ratio of the solvent in the final solution; If precipitation or precipitation occurs in the preparation process, it can be assisted by heating and/or ultrasound.
Protocol 1
Protocol 2

References

[1]Torti D, Sassi F, et al. A preclinical algorithm of soluble surrogate biomarkers that correlate with therapeutic inhibition of the MET oncogene in gastric tumors. Int J Cancer. 2012 Mar 15;130(6):1357-66.

[2]De Bacco F, Luraghi P, et al. 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.

[3]Gentile A, Trusolino L, Comoglio PM. The Met tyrosine kinase receptor in development and cancer. Cancer Metastasis Rev. 2008 Mar;27(1):85-94. doi: 10.1007/s10555-007-9107-6. PMID: 18175071.

[4]Aoyama A, Katayama R, Oh-Hara T, Sato S, Okuno Y, Fujita N. Tivantinib (ARQ 197) exhibits antitumor activity by directly interacting with tubulin and overcomes ABC transporter-mediated drug resistance. Mol Cancer Ther. 2014 Dec;13(12):2978-90. doi: 10.1158/1535-7163.MCT-14-0462. Epub 2014 Oct 13. PMID: 25313010.

[5]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. doi: 10.1158/0008-5472.CAN-10-2100. Epub 2011 Jan 6. PMID: 21212418.

[6]Lolkema MP, Bohets HH, Arkenau HT, Lampo A, Barale E, de Jonge MJA, van Doorn L, Hellemans P, de Bono JS, Eskens FALM. The c-Met Tyrosine Kinase Inhibitor JNJ-38877605 Causes Renal Toxicity through Species-Specific Insoluble Metabolite Formation. Clin Cancer Res. 2015 May 15;21(10):2297-2304. doi: 10.1158/1078-0432.CCR-14-3258. Epub 2015 Mar 5. PMID: 25745036; PMCID: PMC4433755.

[7]Zhan Z, Peng X, Sun Y, Ai J, Duan W. Evaluation of Deuterium-Labeled JNJ38877605: Pharmacokinetic, Metabolic, and in Vivo Antitumor Profiles. Chem Res Toxicol. 2018 Nov 19;31(11):1213-1218. doi: 10.1021/acs.chemrestox.8b00191. Epub 2018 Oct 16. PMID: 30284817.

[8]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.

 

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