JNJ-38877605 (JNJ38877605) is an orally bioavailable small-molecule inhibitor of c-Met with potential antitumor activity. It exhibits 600-fold selectivity for inhibiting c-Met over 200 other kinases and inhibits it with an IC50 of 4 nM.

Physicochemical Properties

Molecular Formula	C19H13F2N7
Molecular Weight	377.35
Exact Mass	377.12
Elemental Analysis	C, 60.48; H, 3.47; F, 10.07; N, 25.98
CAS #	943540-75-8
Related CAS #	943540-75-8
PubChem CID	46911863
Appearance	Off-white to light yellow solid powder
Density	1.5±0.1 g/cm3
Index of Refraction	1.734
LogP	3.13
Hydrogen Bond Donor Count	0
Hydrogen Bond Acceptor Count	7
Rotatable Bond Count	3
Heavy Atom Count	28
Complexity	564
Defined Atom Stereocenter Count	0
SMILES	FC(C1N2C(C=CC(C3=CN(C)N=C3)=N2)=NN=1)(C1C=C2C(N=CC=C2)=CC=1)F
InChi Key	JRWCBEOAFGHNNU-UHFFFAOYSA-N
InChi Code	InChI=1S/C19H13F2N7/c1-27-11-13(10-23-27)16-6-7-17-24-25-18(28(17)26-16)19(20,21)14-4-5-15-12(9-14)3-2-8-22-15/h2-11H,1H3
Chemical Name	6-[difluoro-[6-(1-methylpyrazol-4-yl)-[1,2,4]triazolo[4,3-b]pyridazin-3-yl]methyl]quinoline
Synonyms	JNJ38877605; JNJ 38877605; JNJ-38877605
HS Tariff Code	2934.99.9001
Storage	Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Shipping Condition	Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Biological Activity

Targets	c-Met (IC50 = 4 nM)
ln Vitro	JNJ-38877605 potently inhibits HGF-stimulated and constitutively activated c-Met phosphorylation in vitro and exhibits more than 600-fold selectivity for c-Met when compared to more than 200 other diverse tyrosine and serine-threonine kinases.[1] One important factor in invasive growth that is significantly reduced in EBC1, GTL16, NCI-H1993, and MKN45 cells is JNJ-38877605 (500 nM) phosphorylation of Met and RON.[2] uPAR, IL-6, GROa, and IL-8 secretion in GTL16 cells are all modulated by JNJ-38877605, according to a recent study.
ln Vivo	JNJ-38877605, when administered orally at 40 mg/kg/day for 72 hours in mice with established GTL16 xenografts, causes a statistically significant reduction in human IL-8 plasma levels (from 0.150 ng/mL to 0.050 ng/mL) and GROα plasma levels (from 0.080 ng/mL to 0.030 ng/mL). At the same dosage, however, blood levels of uPAR drop to levels greater than 50%.[3]
Enzyme Assay	JNJ-38877605 is an ATP-competitive inhibitor of c-Met with an IC50 of 4 nM that is 600 times more selective for c-Met than 200 other tyrosine and serine-threonine substrates.
Animal Protocol	GTL16 cells are inoculated subcutaneously into the right posterior flank (or both right and left posterior flanks, for determination of uPAR and IL-6) of 6-week-old immunodeficient nu/nu female mice on Swiss CD1 background. ≤40 mg/kg/day Administered via p.o.
References	[1]. JNJ-38877605: a selective Met kinase inhibitor inducing regression of Met-driven tumor models. [2]. J Natl Cancer Inst . 2011 Apr 20;103(8):645-61. [3]. Int J Cancer . 2012 Mar 15;130(6):1357-66.
Additional Infomation	6-[difluoro-[6-(1-methyl-4-pyrazolyl)-[1,2,4]triazolo[4,3-b]pyridazin-3-yl]methyl]quinoline is a member of quinolines. JNJ-38877605 has been used in trials studying the treatment of Neoplasms. c-Met Inhibitor JNJ-38877605 is an orally bioavailable, small-molecule receptor tyrosine kinase inhibitor with potential antineoplastic activity. c-Met inhibitor JNJ-38877605 selectively inhibits c-Met, a receptor tyrosine kinase (RTK) involved in cancer cell survival and invasiveness, and tumor angiogenesis. c-Met is also known as hepatocyte growth factor receptor (HGFR).

Solubility Data

Solubility (In Vitro)

DMSO: ~37 mg/mL (~98.1 mM) Water: <1 mg/mL Ethanol: <1 mg/mL

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.08 mg/mL (5.51 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.08 mg/mL (5.51 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 3: ≥ 2.08 mg/mL (5.51 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. Solubility in Formulation 4: 30% propylene glycol, 5% Tween 80, 65% D5W: 30 mg/mL  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.6501 mL	13.2503 mL	26.5006 mL
	5 mM	0.5300 mL	2.6501 mL	5.3001 mL
	10 mM	0.2650 mL	1.3250 mL	2.6501 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.