TNF-α

The carboxamide-quinoline LS 2616 is a novel immunomodulator augmenting natural killer (NK) cell activity and T-lymphocyte related effector functions. inoculation of B16-F10 cells significantly reduced tumor take. Continuous treatment of mice with LS 2616 initiated 4 days prior to i.v. injection of tumor cells reduced the number of pulmonary metastases by 85%. When treatment with LS 2616 was started 4 days after i.v. injection of tumor cells, a time when established tumor foci were readily detectable in the lungs, a significant reduction in the number of pulmonary metastases resulted. LS 2616 significantly reduced the number of spontaneous pulmonary metastases developing from a B16-F10 tumor growing in the footpad. When treatment with LS 2616 was initiated after the establishment of grossly visible spontaneous pulmonary metastases, no significant effect on the number of metastases was found after 2 weeks of treatment. However, combined treatment with a dose of cyclophosphamide which in itself was ineffective resulted in a statistically significant 70% reduction in the number of remaining pulmonary metastases. Injection of antibodies to asialomonoganglioside which strongly reduce NK cell activity in various organs was used as a probe for the involvement of NK cells in the effects of LS 2616 on the B16-F10 tumor. The therapeutic efficiency of LS 2616 on tumor take when given from the time of s.c. inoculation, on the number of i.v. induced pulmonary metastases when treatment was started before tumor cell injection, as well as the spontaneous development of pulmonary metastases during exposure to the substance was abrogated by simultaneous injection with antibodies to asialomonoganglioside. In contrast, the beneficial effects of LS 2616 on already established i.v. produced or spontaneous pulmonary metastases were unaltered in mice made NK cell deficient by injection of anti-asialomonoganglioside antibodies. In conclusion, LS 2616 has potent antitumor activities mediated by NK cells as well as non-NK cell related defense mechanisms.[1]

---

Daily oral roquinimex treatment stimulates the immune system and has anticancer efficacy in multiple animal models, this raised the possibility that combining daily oral roquinimex with intermittent cycles of cytotoxic chemotherapy might be a more curative approach for prostate cancer.[2]
The anticancer and antimetastatic responses to roquinimex in rats are associated with a decrease in tumor-infiltrating macrophages and that roquinimex inhibits the ability of rat macrophages to secrete TNF-α, a known angiogenic stimulator, confirming earlier mouse studies. These studies also documented that antitumor, antimetastatic, and antimacrophage effects of roquinimex are unaffected by NK cell depletion in vivo . That human prostate cancer cells growing as xenografts in nude mice are sensitive to apoptotic death induced in vivo by the antiangiogenic effects of roquinimex .[2]

Metabolism / Metabolites
Linomide has known human metabolites that include 4,7-dihydroxy-N,1-dimethyl-2-oxo-N-phenyl-1,2-dihydroquinoline-3-carboxamide, 4-hydroxy-N-(4-hydroxyphenyl)-N,1-dimethyl-2-oxo-1,2-dihydroquinoline-3-carboxamide, 4,6-dihydroxy-N,1-dimethyl-2-oxo-N-phenyl-1,2-dihydroquinoline-3-carboxamide, 4-hydroxy-N-methyl-2-oxo-N-phenyl-1,2-dihydroquinoline-3-carboxamide, 4,8-dihydroxy-N,1-dimethyl-2-oxo-N-phenyl-1,2-dihydroquinoline-3-carboxamide, and 4-hydroxy-1-methyl-2-oxo-N-phenyl-1,2-dihydroquinoline-3-carboxamide.

[1]. PCancer Res . 1986 Jun;46(6):3018-22.

[2]. Expert Opin Investig Drugs . 2010 Oct;19(10):1235-43.

4-hydroxy-N,1-dimethyl-2-oxo-N-phenyl-3-quinolinecarboxamide is an aromatic amide.
Roquinimex is a derivative of quinoline that presents immunostimulant properties. Its effects are suggested to increase the activity of NK cells and macrophage cytotoxicity. Additionally, roquinimex is known to inhibit angiogenesis and to decrease the synthesis of TNF alpha.
Roquinimex is a quinoline-3-carboxamide with potential antineoplastic activity. Roquinimex inhibits endothelial cell proliferation, migration, and basement membrane invasion; reduces the secretion of the angiogenic factor tumor necrosis factor alpha by tumor-associated macrophages (TAMs); and inhibits angiogenesis. This agent is also an immune modulator that appears to alter cytokine profiles and enhance the activity of T cells, natural killer cells, and macrophages. (NCI04)

---

Drug Indication
Roquinimex is investigated to be used as a treatment of a number of cancers and autoimmune conditions. As well, roquinimex is researched to be used as adjuvant therapy after bone marrow transplantation in cases of acute leukemia.

C18H16N2O3

308.33

308.116

C, 70.12; H, 5.23; N, 9.09; O, 15.57

84088-42-6

54676478

White to off-white solid powder

1.4±0.1 g/cm3

436.2±45.0 °C at 760 mmHg

204 °C(dec.)

217.6±28.7 °C

0.0±1.1 mmHg at 25°C

1.686

1.65

1

3

2

23

522

0

O=C(N(C)C1C=CC=CC=1)C1=C(O)C2C(=CC=CC=2)N(C)C1=O

SGOOQMRIPALTEL-UHFFFAOYSA-N

InChI=1S/C18H16N2O3/c1-19(12-8-4-3-5-9-12)17(22)15-16(21)13-10-6-7-11-14(13)20(2)18(15)23/h3-11,21H,1-2H3

4-hydroxy-N,1-dimethyl-2-oxo-N-phenylquinoline-3-carboxamide

Roquinimex; FCF-89; FCF 89; FCF89; LS2616; LS 2616; LS-2616; Linomide. Trade name: Linomide

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.

---

Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)
*Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution.
Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)
Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil)
Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals).

View More

Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)]
*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.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)

---

Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium)
Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose
Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals).

View More

Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders

---

Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

---

 (Please use freshly prepared in vivo formulations for optimal results.)