Category: 115204-76-7

Lin, Guimiao published the artcileA conjugate of octamer-binding transcription factor 4 and toll-like receptor 7 agonist prevents the growth and metastasis of testis embryonic carcinoma, Formula: C13H7Cl2N5, the publication is Journal of Translational Medicine (2015), 1-20, database is CAplus and MEDLINE.

Background: The immune non-recognition is often the underlying cause of failure in tumor immunotherapeutic. This is because most tumor-related antigens are poorly immunogenic, and fail to arouse an efficient immune response against cancers. Here we synthesized a novel TLR7 agonist, and developed a safe and effective immunotherapeutic vaccine by conjugating this TLR7 agonist with the pluripotency antigen OCT4. Methods: Purified recombinant OCT4 protein was covalently linked with a novel TLR7 agonist to form a TLR7-OCT4 conjugate (T7-OCT4). After conjugation, the in vitro release of IL-12 and IFN-γ was observed in spleen lymphocytes. Mice were immunized with TLR7-OCT4, and the release of IFN-γ, the percentages of CD3+/CD8+ T cells and the OCT4-specific cytotoxicity rates were measured. The immunized mice were challenged with mouse embryonic carcinoma (EC), and the tumor volume and tumor weight were determined Blood routine examination was performed to evaluate the biosafety of TLR7 agonist and TLR7-OCT4 conjugate in mice. Results T7-OCT4 conjugate significantly increased the in vitro release of IL-12 and IFN-γ by mouse spleen lymphocytes. In addition, the release of IFN-γ, the percentages of CD3+/CD8+ T cells and the tumor-specific cytotoxicity rates in immunized mice were significantly higher. Importantly, in EC xenografted mice, immunization with T7-OCT4 conjugate decreased the growth of the tumor dramatically up to 90 %, as compared to mice immunized with OCT4 protein or TLR7 agonist alone. Furthermore, blood routine examination demonstrated that no abnormalities of the blood cells and components in the blood fluids were detected by T7-OCT4 and TLR7 agonist injections. Conclusions: Our results showed that conjugating OCT4 protein to the novel TLR7 agonist produced a vaccine which is effective and safe in preventing tumor growth in mice. Our results suggest that this type of vaccine formulation has great potentiality in preventive vaccines against OCT4 expressing tumors.

Journal of Translational Medicine published new progress about 115204-76-7. 115204-76-7 belongs to nitriles-buliding-blocks, auxiliary class 5.6_Aromatics,Purines, name is 4-((2,6-Dichloro-9H-purin-9-yl)methyl)benzonitrile, and the molecular formula is C13H7Cl2N5, Formula: C13H7Cl2N5.

Referemce:
https://en.wikipedia.org/wiki/Nitrile,
Nitriles – Chemistry LibreTexts

Kelley, James L. published the artcile9-Benzyl-6-(dimethylamino)-9H-purines with antirhinovirus activity, Related Products of nitriles-buliding-blocks, the publication is Journal of Medicinal Chemistry (1988), 31(10), 2001-4, database is CAplus and MEDLINE.

A series of 9-benzyl-6-(dimethylamino)-9H-purines and 9-benzyl-2-chloro-6-(dimethylamino)-9H-purines were synthesized and tested in cell culture for activity against rhinovirus type 1B. The 9-benzylpurines that were unsubstituted in the 2-position had weak activity. However, introduction of a 2-chloro substituent resulted in a substantial increase in antiviral activity. One of the most active compounds, 2-chloro-6-(dimethylamino)-9-(4-methylbenzyl)-9H-purine (I, R = Me), had an IC₅₀ value of 0.08 μM against serotype 1B. I (R = Cl, Me, Et, Me₂CH) were tested against 18 other rhinovirus serotypes, but the majority tested were less sensitive than type 1B. The range of serotype sensitivity for I (R = Me) varied from 0.08 to 14 μM. These 9-benzyl-2-chloro-9H-purines represent a new class of antiviral agents with in vitro activity against rhinoviruses.

Journal of Medicinal Chemistry published new progress about 115204-76-7. 115204-76-7 belongs to nitriles-buliding-blocks, auxiliary class 5.6_Aromatics,Purines, name is 4-((2,6-Dichloro-9H-purin-9-yl)methyl)benzonitrile, and the molecular formula is C13H7Cl2N5, Related Products of nitriles-buliding-blocks.

Referemce:
https://en.wikipedia.org/wiki/Nitrile,
Nitriles – Chemistry LibreTexts

Wu, Christina C. N. published the artcileImmunotherapeutic activity of a conjugate of a Toll-like receptor 7 ligand, Quality Control of 115204-76-7, the publication is Proceedings of the National Academy of Sciences of the United States of America (2007), 104(10), 3990-3995, database is CAplus and MEDLINE.

The immunotherapeutic activity of Toll-like receptor (TLR) activators has been difficult to exploit because of side effects related to the release and systemic dispersion of proinflammatory cytokines. To overcome this barrier, we have synthesized a versatile TLR7 agonist, 4-[6-amino-8-hydroxy-2-(2-methoxyethoxy)purin-9-ylmethyl]benzaldehyde (UC-1V150), bearing a free aldehyde that could be coupled to many different auxiliary chem. entities through a linker mol. with a hydrazine or amino group without any loss of activity. UC-1V150 was covalently coupled to mouse serum albumin (MSA) at a 5:1 molar ratio to yield a stable mol. with a characteristically altered UV spectrum. Compared with the unconjugated TLR7 agonist, the UC-1V150/MSA was a 10-to 100-fold more potent inducer of cytokine production in vitro by mouse bone marrow-derived macrophage and human peripheral blood mononuclear cells. When administered to the lung, the conjugate induced a prolonged local release of cytokines at levels 10-fold or more higher than those found in serum. Under the same conditions, the untethered TLR7 ligand induced quick systemic cytokine release with resultant toxicity. In addition, two pulmonary infectious disease models were investigated wherein mice were pretreated with the conjugate and then challenged with either Bacillus anthracis spores or HIN1 influenza A virus. Significant delay in mortality was observed in both disease models with UC-1V150/MSA-pretreated mice, indicating the potential usefulness of the conjugate as a localized and targeted immunotherapeutic agent.

Proceedings of the National Academy of Sciences of the United States of America published new progress about 115204-76-7. 115204-76-7 belongs to nitriles-buliding-blocks, auxiliary class 5.6_Aromatics,Purines, name is 4-((2,6-Dichloro-9H-purin-9-yl)methyl)benzonitrile, and the molecular formula is C9H8O4, Quality Control of 115204-76-7.

Referemce:
https://en.wikipedia.org/wiki/Nitrile,
Nitriles – Chemistry LibreTexts

Gadd, Adam J. R. published the artcileHigh potency of lipid conjugated TLR7 agonist requires nanoparticulate or liposomal formulation, COA of Formula: C13H7Cl2N5, the publication is European Journal of Pharmaceutical Sciences (2018), 268-276, database is CAplus and MEDLINE.

Here, we studied the effect of formulation on potency of a 1,2-di-(9Z-octadecenoyl)-sn-glycero-3-phosphoethanolamine (DOPE) conjugated TLR7 agonist (DOPE-TLR7a) alongside assessing phys. form using Dynamic Light Scattering (DLS), Nanosight Particle Tracking (NTA) anal. and Small Angle X-ray Scattering (SAXS). A very high potency of DOPE-TLR7a conjugate (EC₅₀ around 9 nM) was observed either when prepared by direct dilution from DMSO or when formulated into 400-700 nm large multilamella liposomes containing dimethyldioctadecylammonium bromide salt (DDA) and DOPE. When prepared by dissolution in DMSO followed by dilution in aqueous culture medium, 93 ± 5 nm nanoparticles were formed. Without dilution from solution in DMSO, no nanoparticles were observed and no immunostimulatory activity could be detected without this formulation step. SAXS anal. of the conjugate after DMSO dissolution/water dilution revealed a lamellar order with a layer spacing of 68.7 Å, which correlates with arrangement in groups of 3 bilayers. The addition of another immunostimulatory glycolipid, trehalose-6,6-dibehenate (TDB), to DOPE:DDA liposomes gave no further increase in immunostimulatory activity beyond that provided by incorporating DOPE-TLR7a. Given the importance of nanoparticle or liposomal formulation for activity, we conclude that the major mechanism for increased potency when TLR7 agonists are conjugated to macromols. is through alteration of phys. form.

European Journal of Pharmaceutical Sciences published new progress about 115204-76-7. 115204-76-7 belongs to nitriles-buliding-blocks, auxiliary class 5.6_Aromatics,Purines, name is 4-((2,6-Dichloro-9H-purin-9-yl)methyl)benzonitrile, and the molecular formula is C13H7Cl2N5, COA of Formula: C13H7Cl2N5.

Referemce:
https://en.wikipedia.org/wiki/Nitrile,
Nitriles – Chemistry LibreTexts