Tag: M.W=200-250

Gil-Martinez, Jon published the artcileTherapeutic targeting of fumaryl acetoacetate hydrolase in hereditary tyrosinemia type I, Safety of 3-Amino-4-methyl-N-(4-methyl-2-pyridyl)benzamide, the publication is International Journal of Molecular Sciences (2021), 22(4), 1789, database is CAplus and MEDLINE.

Fumarylacetoacetate hydrolase (FAH) is the fifth enzyme in the tyrosine catabolism pathway. A deficiency in human FAH leads to hereditary tyrosinemia type I (HT1), an autosomal recessive disorder that results in the accumulation of toxic metabolites such as succinylacetone, maleylacetoacetate, and fumarylacetoacetate in the liver and kidney, among other tissues. The disease is severe and, when untreated, it can lead to death. A low tyrosine diet combined with the herbicidal nitisinone constitutes the only available therapy, but this treatment is not devoid of secondary effects and long-term complications. In this study, we targeted FAH for the first-time to discover new chem. modulators that act as pharmacol. chaperones, directly associating with this enzyme. After screening several thousand compounds and subsequent chem. redesign, we found a set of reversible inhibitors that associate with FAH close to the active site and stabilize the (active) dimeric species, as demonstrated by NMR spectroscopy. Importantly, the inhibitors are also able to partially restore the normal phenotype in a newly developed cellular model of HT1.

International Journal of Molecular Sciences published new progress about 1019398-93-6. 1019398-93-6 belongs to amides-buliding-blocks, auxiliary class Pyridine,Amine,Benzene,Amide, name is 3-Amino-4-methyl-N-(4-methyl-2-pyridyl)benzamide, and the molecular formula is C14H15N3O, Safety of 3-Amino-4-methyl-N-(4-methyl-2-pyridyl)benzamide.

Referemce:
https://en.wikipedia.org/wiki/Amide,
Amide – an overview | ScienceDirect Topics

Stolley, Ryan M. published the artcileNickel-Catalyzed [2+2+2] Cycloaddition of Diynes and Cyanamides, SDS of cas: 2451-91-4, the publication is European Journal of Organic Chemistry (2011), 2011(20-21), 3815-3824, database is CAplus and MEDLINE.

A variety of bicyclic N,N-disubstituted 2-aminopyridines have been prepared from diynes and cyanamides by nickel-catalyzed [2+2+2] cycloaddition reactions. The reactions proceeded at room temperature with low catalyst loading to afford 2-aminopyridines in good to excellent yields. E.g., in presence of Ni(cod)₂ and IMes [1,3-bis(2,4,6-trimethylphenyl)imidazol-2-ylidene], [2+2+2] cycloaddition of MeCCCH₂C(CO₂Me)₂CH₂CCMe and N-cyanopyrrolidine gave 98% 2-aminopyridine derivative I. The method is amenable to both internal and terminal diynes and proceeds in a regioselective manner. A number of cyanamides with diverse functional group tolerance were used. The intermol. version employing 3-hexyne and N-cyanopyrrolidine also afforded the desired N,N-disubstituted 2-aminopyridine in good yield.

European Journal of Organic Chemistry published new progress about 2451-91-4. 2451-91-4 belongs to amides-buliding-blocks, auxiliary class Nitrile,Amine,Benzene, name is N,N-Dibenzylcyanamide, and the molecular formula is C5H7N3S3, SDS of cas: 2451-91-4.

Referemce:
https://en.wikipedia.org/wiki/Amide,
Amide – an overview | ScienceDirect Topics

Dong, Peng published the artcileThe enhanced antitumor activity of the polymeric conjugate covalently coupled with docetaxel and docosahexaenoic acid, Formula: C11H22N2O4, the publication is Biomaterials Science (2022), 10(13), 3454-3465, database is CAplus and MEDLINE.

Docetaxel (DTX) has been widely used for the treatment of many types of cancer. However, DTX is poorly water-soluble and com. DTX is formulated in non-ionic surfactant polysorbate 80 and ethanol, thereby leading to hypersensitivity and serious side effects. Herein, a polymer dual drug conjugate was synthesized by coupling DTX and docosahexaenoic acid (DHA) with bifunctionalized dextran. The polysaccharide conjugate dextran-DHA-DTX possessed high water solubility and was self-assembled into nanoparticles with a diameter of 98.0 ± 6.4 nm. Pharmacokinetic and biodistribution studies showed that the dextran-DHA-DTX dual drug conjugate not only had significantly prolonged blood circulation but was also selectively accumulated in the tumor with reduced drug distribution in normal tissues. The conjugate exhibited a superior therapeutic effect in both xenograft nude mice models without causing any systemic side effects. Notably, the conjugate nearly eliminated all xenograft tumors in nude mice bearing breast cancer cells MCF-7. This study revealed that the dextran-based dual drug delivery system may provide an effective strategy to selectively deliver DTX to tumor sites.

Biomaterials Science published new progress about 2418-95-3. 2418-95-3 belongs to amides-buliding-blocks, auxiliary class Chiral,Carboxylic acid,Amine,Aliphatic hydrocarbon chain,Ester,Amino acide derivatives, name is H-Lys(Boc)-OH, and the molecular formula is C11H22N2O4, Formula: C11H22N2O4.

Referemce:
https://en.wikipedia.org/wiki/Amide,
Amide – an overview | ScienceDirect Topics

Zhu, Yongyan published the artcileVinblastine-Loaded Nanoparticles with Enhanced Tumor-Targeting Efficiency and Decreasing Toxicity: Developed by One-Step Molecular Imprinting Process, Name: H-Lys(Boc)-OH, the publication is Molecular Pharmaceutics (2019), 16(6), 2675-2689, database is CAplus and MEDLINE.

Molecularly imprinted polymers have exhibited good performance as carriers on drug loading and sustained release. In this paper, vinblastine (VBL)-loaded polymeric nanoparticles (VBL-NPs) were prepared by a one-step mol. imprinting process, avoiding the waste and incomplete removal of the template, and evaluated as targeting carriers for VBL delivery after modification. Using acryloyl amino acid comonomers and disulfide cross-linkers, VBL-NPs were synthesized and then conjugated with poly(ethylene glycol)-folate. The dynamic size of the obtained VBL-NPs-PEG-FA was 258.3 nm (PDI = 0.250), and the encapsulation efficiency was 45.82 ± 1.45%. The nanoparticles of VBL-NPs-PEG-FA were able to completely release VBL during 48 h under a mimic tumor intracellular condition (pH 4.5, 10 mM glutathione (GSH)), displaying significant redox responsiveness, whereas the release rates were much slower in the mimic body liquid (pH 7.4, 2μM GSH) and tumor extracellular environment (pH 6.5, 2μM GSH). Furthermore, the carriers NPs-PEG-FA, prepared without VBL, showed satisfactory intrinsic hemocompatibility, cellular compatibility, and tumor-targeting properties: they could rapidly and efficiently accumulate to folate receptor pos. Hela cells and then internalized via receptor-mediated endocytosis, and the retention in tumor tissues could last for over 48 h. Interestingly, VBL-NPs-PEG-FA could evidently increase the accumulation of VBL in tumor tissues while decreasing the distribution of VBL in organs, exert similar anticancer efficacy against Hela tumors in the xenograft model of nude mice to VBL injection, and significantly improve the abnormality of liver and spleen observed in VBL injection. VBL-NPs-PEG-FA has the potential to be the delivery carrier for VBL by enhancing the tumor-targeting efficacy of VBL and decreasing toxicity to normal tissues.

Molecular Pharmaceutics published new progress about 2418-95-3. 2418-95-3 belongs to amides-buliding-blocks, auxiliary class Chiral,Carboxylic acid,Amine,Aliphatic hydrocarbon chain,Ester,Amino acide derivatives, name is H-Lys(Boc)-OH, and the molecular formula is C13H15NO6S, Name: H-Lys(Boc)-OH.

Referemce:
https://en.wikipedia.org/wiki/Amide,
Amide – an overview | ScienceDirect Topics

Li, Wenjing published the artcileDiesel exhaust particle promotes tumor lung metastasis via the induction of BLT1-mediated neutrophilic lung inflammation, COA of Formula: C12H23N3S, the publication is Cytokine+ (2018), 530-540, database is CAplus and MEDLINE.

BLT1, the primary functional receptor of Leukotriene B4 (LTB4), is involved in tissue inflammation by mediating leukocyte recruitment, and recently LTB4-dependent inflammation was reported to promote lung tumor growth. In this study, we found that DEP exposure led to acute lung inflammation, characterized by abundant infiltration of neutrophils and elevated lung levels in LTB4, as well as several pro-inflammatory cytokines and chemokines, including IL-1β, IL-6, TNF-α, CXCL1/2. BLT1 blockade by its specific antagonist U75302 significantly inhibited neutrophilic lung inflammation following DEP exposure. Importantly, BLT1 blockade before the onset of inflammation significantly reduced DEP-enhanced lung metastasis, which was associated with greatly decreased infiltrating neutrophils in lungs. Interestingly, BLT1 blockade after the occurrence of lung metastases had no effect on the magnitude of lung metastasis, suggesting that inhibition of BLT1-mediated lung inflammation was insufficient to suppress established metastatic tumor. Administration of BLT2 inhibitor LY255283 fails to inhibit DEP-induced lung inflammation and tumor metastasis. Collectively, our results demonstrate that DEP exposure causes BLT1-mediated lung neutrophilic inflammation, which is critical for tumor lung metastasis, and suggest that interruption of the LTB4-BLT1 axis could be useful for preventing PM_2.5-induced inflammation and subsequent susceptible to lung metastasis.

Cytokine+ published new progress about 321673-30-7. 321673-30-7 belongs to amides-buliding-blocks, auxiliary class Immunology/Inflammation,Scavenger receptor, name is [(2-Hexylcyclopentylidene)amino]thiourea, and the molecular formula is C12H23N3S, COA of Formula: C12H23N3S.

Referemce:
https://en.wikipedia.org/wiki/Amide,
Amide – an overview | ScienceDirect Topics

Yang, Fangping published the artcileFacile Preparation of Polysaccharide-Polypeptide Conjugates via a Biphasic Solution Ring-Opening Polymerization, Category: amides-buliding-blocks, the publication is ACS Macro Letters (2022), 11(5), 663-668, database is CAplus and MEDLINE.

Polysaccharide-polypeptide conjugates have gained a broad interest in mimicking the structure and bioactivity of peptidoglycans or proteoglycans for biomedical applications. Efficient and precise preparation of the conjugates is challenging and unresolved, mainly because of the mismatched solubility between polysaccharide initiators and N-carboxyanhydrides (NCAs), which frequently results in competing side reactions and oligomeric polypeptide chain. Herein, we report a facile and efficient strategy to prepare the conjugates with well-controlled polypeptide chain length (l_p) directly from unmodified polysaccharides via a biphasic solution ring-opening polymerization The effect of l_p on surface antibacterial properties has been investigated. Elongating the l_p can significantly potentiate the antibiofilm property of the conjugate coatings. Our results may provide opportunities to develop various polypeptide-based conjugates with well-defined structures toward versatile uses.

ACS Macro Letters published new progress about 2418-95-3. 2418-95-3 belongs to amides-buliding-blocks, auxiliary class Chiral,Carboxylic acid,Amine,Aliphatic hydrocarbon chain,Ester,Amino acide derivatives, name is H-Lys(Boc)-OH, and the molecular formula is C8H11NO, Category: amides-buliding-blocks.

Referemce:
https://en.wikipedia.org/wiki/Amide,
Amide – an overview | ScienceDirect Topics

Prado, Morgana K. B. published the artcileLeukotriene B₄ is essential for lung host defence and alpha-defensin-1 production during Achromobacter xylosoxidans infection, Related Products of amides-buliding-blocks, the publication is Scientific Reports (2017), 7(1), 1-13, database is CAplus and MEDLINE.

Leukotriene B₄ (LTB₄) is essential for host immune defense. It increases neutrophil recruitment, phagocytosis and pathogen clearance, and decreases edema and inflammasome activation. The host response and the role of LTB₄ during Achromobacter xylosoxidans infection remain unexplored. Wild-type (129sv) and LTB₄ deficient (Alox5^-/-) mice were intratracheally infected with A. xylosoxidans. Wild-type 129sv infected mice survived beyond the 8th day post-infection, exhibited increased levels of LTB₄ in the lung on the 1st day, while levels of PGE₂ increased on the 7th day post-infection. Infected Alox5^-/- mice showed impaired bacterial clearance, increased lung inflammation, and succumbed to the infection by the 7th day. We found that exogenous LTB₄ does not affect the phagocytosis of A. xylosoxidans by alveolar macrophages in vitro. However, treatment of infected animals with LTB₄ protected from mortality, by reducing the bacterial load and inflammation via BLT₁ signalling, the high affinity receptor for LTB₄. Of importance, we uncovered that LTB₄ induces gene and protein expression of α-defensin-1 during the infection. This mol. is essential for bacterial clearance and exhibits potent antimicrobial activity by disrupting A. xylosoxidans cell wall. Taken together, our data demonstrate a major role for LTB₄ on the control of A. xylosoxidans infection.

Scientific Reports published new progress about 321673-30-7. 321673-30-7 belongs to amides-buliding-blocks, auxiliary class Immunology/Inflammation,Scavenger receptor, name is [(2-Hexylcyclopentylidene)amino]thiourea, and the molecular formula is C12H23N3S, Related Products of amides-buliding-blocks.

Referemce:
https://en.wikipedia.org/wiki/Amide,
Amide – an overview | ScienceDirect Topics

Serfling, Robert published the artcileDesigner tRNAs for efficient incorporation of non-canonical amino acids by the pyrrolysine system in mammalian cells, Formula: C11H22N2O4, the publication is Nucleic Acids Research (2018), 46(1), 1-10, database is CAplus and MEDLINE.

The pyrrolysyl-tRNA synthetase/tRNAPyl pair is the most versatile and widespread system for the incorporation of non-canonical amino acids (ncAAs) into proteins in mammalian cells. However, low yields of ncAA incorporation severely limit its applicability to relevant biol. targets. Here, we generate two tRNAPyl variants that significantly boost the performance of the pyrrolysine system. Compared to the original tRNAPyl, the engineered tRNAs feature a canonical hinge between D- and T-loop, show higher intracellular concentrations and bear partially distinct post-transcriptional modifications. Using the new tRNAs, we demonstrate efficient ncAA incorporation into a G-protein coupled receptor (GPCR) and simultaneous ncAA incorporation at two GPCR sites. Moreover, by incorporating last-generation ncAAs for bioorthogonal chem., we achieve GPCR labeling with small organic fluorophores on the live cell and visualize stimulus-induced GPCR internalization. Such a robust system for incorporation of single or multiple ncAAs will facilitate the application of a wide pool of chem. tools for structural and functional studies of challenging biol. targets in live mammalian cells.

Nucleic Acids Research published new progress about 2418-95-3. 2418-95-3 belongs to amides-buliding-blocks, auxiliary class Chiral,Carboxylic acid,Amine,Aliphatic hydrocarbon chain,Ester,Amino acide derivatives, name is H-Lys(Boc)-OH, and the molecular formula is C5H4N2O, Formula: C11H22N2O4.

Referemce:
https://en.wikipedia.org/wiki/Amide,
Amide – an overview | ScienceDirect Topics

Zheng, Hao published the artcileDownregulation of COX-2 and CYP 4A signaling by isoliquiritigenin inhibits human breast cancer metastasis through preventing anoikis resistance, migration and invasion, Quality Control of 321673-30-7, the publication is Toxicology and Applied Pharmacology (2014), 280(1), 10-20, database is CAplus and MEDLINE.

Flavonoids exert extensive in vitro anti-invasive and in vivo anti-metastatic activities. Anoikis resistance occurs at multiple key stages of the metastatic cascade. Here, we demonstrate that isoliquiritigenin (ISL), a flavonoid from Glycyrrhiza glabra, inhibits human breast cancer metastasis by preventing anoikis resistance, migration and invasion through downregulating cyclooxygenase (COX)-2 and cytochrome P 450 (CYP) 4A signaling. ISL induced anoikis in MDA-MB-231 and BT-549 human breast cancer cells as evidenced by flow cytometry and the detection of caspase cleavage. Moreover, ISL inhibited the mRNA expression of phospholipase A2, COX-2 and CYP 4A and decreased the secretion of prostaglandin E₂ (PGE₂) and 20-hydroxyeicosatetraenoic acid (20-HETE) in detached MDA-MB-231 cells. In addition, it decreased the levels of phospho-PI3K (Tyr⁴⁵⁸), phospho-PDK (Ser²⁴¹) and phospho-Akt (Thr³⁰⁸). Conversely, the exogenous addition of PGE₂, WIT003 (a 20-HETE analog) and an EP4 agonist (CAY10580) or overexpression of constitutively active Akt reversed ISL-induced anoikis. ISL exerted the in vitro anti-migratory and anti-invasive activities, whereas the addition of PGE₂, WIT003 and CAY10580 or overexpression of constitutively active Akt reversed the in vitro anti-migratory and anti-invasive activities of ISL in MDA-MB-231 cells. Notably, ISL inhibited the in vivo lung metastasis of MDA-MB-231 cells, together with decreased intratumoral levels of PGE₂, 20-HETE and phospho-Akt (Thr³⁰⁸). In conclusion, ISL inhibits breast cancer metastasis by preventing anoikis resistance, migration and invasion via downregulating COX-2 and CYP 4A signaling. It suggests that ISL could be a promising multi-target agent for preventing breast cancer metastasis, and anoikis could represent a novel mechanism through which flavonoids may exert the anti-metastatic activities.

Toxicology and Applied Pharmacology published new progress about 321673-30-7. 321673-30-7 belongs to amides-buliding-blocks, auxiliary class Immunology/Inflammation,Scavenger receptor, name is [(2-Hexylcyclopentylidene)amino]thiourea, and the molecular formula is C7H8BClO2, Quality Control of 321673-30-7.

Referemce:
https://en.wikipedia.org/wiki/Amide,
Amide – an overview | ScienceDirect Topics

Kwon, Hongmok published the artcileStructure-activity relationship studies of prostate-specific membrane antigen (PSMA) inhibitors derived from α-amino acid with (S)- or (R)-configuration at P1′ region, HPLC of Formula: 2418-95-3, the publication is Bioorganic Chemistry (2020), 104304, database is CAplus and MEDLINE.

Prostate-specific membrane antigen (PSMA), a type II membrane glycoprotein, is considered an excellent target for the diagnosis or treatment of prostate cancer. We previously investigated the effect of β- and γ-amino acids with (S)- or (R)-configuration in the S1 pocket on the binding affinity for PSMA. However, comprehensive studies on the effect of α-amino acid with (R)-configuration in the S1′ pocket has not been reported yet. We selected ZJ-43 (1) and DCIBzL (5) as templates and synthesized their analogs with (S)- or (R)-configuration in the P1 and P1′ regions. The PSMA-inhibitory activities of compounds with altered chirality in the P1′ region were dropped dramatically, with their IC₅₀ values changing from nM to μM ranges. The compounds with (S)-configuration at both P1 and P1′ regions were more potent than the others. The findings of this study may provide insights regarding the structural modification of PSMA inhibitor in the S1′ binding pocket.

Bioorganic Chemistry published new progress about 2418-95-3. 2418-95-3 belongs to amides-buliding-blocks, auxiliary class Chiral,Carboxylic acid,Amine,Aliphatic hydrocarbon chain,Ester,Amino acide derivatives, name is H-Lys(Boc)-OH, and the molecular formula is C11H22N2O4, HPLC of Formula: 2418-95-3.

Referemce:
https://en.wikipedia.org/wiki/Amide,
Amide – an overview | ScienceDirect Topics