mrna

CD19 car mRNA-LNP, a lipid nanoparticle (LNP) encapsulating CD19 car mRNA, is instrumental in assessing RNA delivery, translation efficacy, and cell viability among other applications. This compound is pivotal for chimeric antigen receptor T cell immunotherapy (CAR-CD19), leveraging the CD19 molecule - a critical membrane antigen expressed by B cells (i.e., leukocyte differentiation antigen) that plays a significant role in their proliferation, differentiation, activation, and antibody production, as well as enhancing BCR signal transduction [1] [2].

The COVID-19 Spike Protein mRNA, responsible for expressing the COVID-19 spike protein, is crucial for evaluating RNA delivery, translation efficiency, and cell viability. Positioned on the membrane surface, this spike protein facilitates virus entry into cells by binding to host cell membrane receptors and promoting membrane fusion. It serves as a significant action site for neutralizing antibodies and represents a primary focus in vaccine development [1].

mRNA-Encapsulating Lipid Excipient 1 (Compound 2), a thiocarbamate-based ionizable lipid, serves as an excipient in the formulation of mRNA-encapsulating lipid nanoparticles [1].

COVID-19 Spike Protein mRNA-LNP is a lipid nanoparticle (LNP) formulated with the novel coronavirus pneumonia spike protein, positioned on the membrane surface. It is designed for applications such as RNA delivery, translation efficiency, and cell viability assessment. This spike protein facilitates the COVID-19 virus's entry into host cells by binding to cell membrane receptors and enabling membrane fusion, making it a critical focal point for host neutralizing antibodies and vaccine development [1].

CD19 CAR mRNA is designed to express the CD19 chimeric antigen receptor (CAR) protein, pivotal in chimeric antigen receptor T cell (CAR-CD19) immunotherapy. This receptor targets CD19, a membrane antigen crucial for B cell proliferation, differentiation, activation, and antibody synthesis, playing a significant role in promoting BCR signal transduction.

TVB-3664 significantly decreases tubulin palmitoylation and mRNA expression. TVB-3664 is a reversible and highly bioavailable fatty acid synthase inhibitor (IC50: 18 nM and 12 nM for human and mouse cell palmitate synthesis, respectively).

SM-102 is an ionizable amino lipid utilized in the synthesis of lipid nanoparticles (LNPs)[1]. It exhibits promise in the creation of LNPs dedicated to the transportation of mRNA-based vaccines[2].

Risdiplam (RO7034067) (RG7916) is orally administered. Risdiplam is a centrally and peripherally distributed SMN2 pre-mRNA splicing modifier which increases survival motor neuron (SMN) protein levels[1].

Ceramides Mixture, an endogenous ceramide, consists of hydroxy and non-hydroxy fatty acid-containing ceramides. It is involved in the regulation of cell cycle arrest, growth inhibition, and modulation of telomerase activity.

Taurochenodeoxycholic Acid (12-Deoxycholyltaurine) is one of the main bioactive substances of animals' bile acid.

Ethyl gallate (gallic acid ethyl ester) obviously decreases cell proliferation in MDA-MB-231 and MCF-7 cells in a dose- and time-dependent manner, exhibits cytotoxicity in a dose-dependent manner. Ethyl gallate can inhibit the abilities of invasion of breast cancer in vitro by inhibiting the mRNA levels of MMP-9/MMP-2, phosphorylation of Akt and protein expression of NF-κB and inhibits hydrogen peroxide signaling, may represent an alternative class of vasopressors for use in septic shock. Also, Ethyl gallate suppresses proliferation and invasion in human breast cancer cells by modulating the PI3K/Akt pathway, which may contribute to inhibiting their downstream targets such as NF-κB p-65, Bcl-2/Bax, and mRNA levels of MMP-2 and MMP-9 in breast cancer cells, could be used as potential antioxidants with safe therapeutic application in cancer chemotherapy.

Tetracycline hydrochloride (NCI-c55561) is the hydrochloride salt of the tetracycline, a broad-spectrum naphthacene antibiotic produced semisynthetically from chlortetracycline, an antibiotic isolated from the bacterium Streptomyces aureofaciens. In bacteria, tetracycline blocks binding of aminoacyl-tRNA to the mRNA-ribosome complex, thereby inhibiting protein synthesis and bacterial cell growth. Because naturally, fluorescing tetracycline binds to a newly formed bone at the bone/osteoid interface, tetracycline-labeling of bone and fluorescence microscopy may be used to perform bone histomorphometry.

Enoxacin (NSC-629661) is a broad-spectrum 6-fluoronaphthyridinone antibacterial agent (fluoroquinolones) structurally related to nalidixic acid.

Oxytetracycline Hydrochloride (Dalimycin) is a tetracycline derivative produced by Streptomyces rimosus with antimicrobial activity. It interferes with the binding of aminoacyl-tRNA to the mRNA-ribosome complex, resulting in preventing peptide elongation and inhibiting protein synthesis.

Mevastatin (ML236B) is an HMG-CoA reductase inhibitor that was initially isolated from the mold Pythium ultimum. Mevastatin was the first statin to enter clinical trials.

Tigecycline (GAR-936) is a broad-spectrum glycylcycline antibiotic derived from tetracycline that binds to the 30S ribosomal subunit, disrupting the binding of aminoacyl-tRNA to the mRNA-ribosome complex.

Kasugamycin hydrochloride hydrate (Ksg (hydrochloride hydrate))(Ksg) specifically inhibits translation initiation of canonical but not of leaderless messenger RNAs. Ksg inhibition is thought to occur by direct competition with initiator transfer RNA

Pyrrolidinedithiocarbamate ammonium (1-Pyrrolidinedithiocarboxylic acid ammonium salt), a selective NF-κB inhibitor, inhibits translation of nitric oxide synthase mRNA to prevent induction.

Enoxacin hydrate (AT-2266 hydrate) is a broad-spectrum 6-fluoronaphthyridinone antibacterial agent.

Kasugamycin hydrochloride (Kasumin) is an aminoglycoside antibiotic that was originally isolated in 1965, from Streptomyces kasugaensis, a Streptomyces strain found near the Kasuga shrine in Nara, Japan. Kasugamycin hydrochloride was discovered by Hamao Umezawa, who also discovered kanamycin and bleomycin, as a drug which could prevent growth of a fungus causing rice blast disease.

Budesonide (Pulmicort), an anti-inflammatory corticosteroid, has shown the effective glucocorticoid activitie and few mineralocorticoid activities. According to reports, Budesonide has extensively inhibitory effects against multiple cells types and mediators referred to allergic and nonallergic-mediated inflammatory. What's more, the anti-inflammatory action of budesonide has been revealed to contribute to the effectiveness of asthma.

Paromomycin binds specifically to the RNA oligonucleotide at the A site of bacterial 30S ribosomes, thereby causing misreading and premature termination of translation of mRNA and inhibition of protein synthesis followed by cell death. Paromomycin Sulfate (Aminosidine sulfate) is the sulfate salt form of paromomycin, a structural derivative of neomycin, an aminoglycoside antibiotic with amebicidal and bactericidal effects against predominantly aerobic gram-negative bacteria.

1. 2,5-Dihydroxyacetophenone (Quinacetophenone) possess anti-anxiety, and neuroprotective qualities. 2. 2,5-Dihydroxyacetophenone (Quinacetophenone) reatment can induce a sustained activation of JNK, ERK1/2, and p38 MAPKs, it also can potentiate the pro-apoptotic and anti-proliferative effects of bortezomib in U266 cells. 3. 2,5-Dihydroxyacetophenone (Quinacetophenone) has anti-inflammatory activity in activated macrophages, raising the possibility that this compound has a therapeutic potential for inflammatory conditions. 4. 2,5-Dihydroxyacetophenone (Quinacetophenone) is an uncompetitive inhibitor of murine tyrosinase (K(I) 0.28mm), it strongly inhibits both melanogenesis and cellular tyrosinase activity in vitro in 3-isobutyl-1-methylxanthin-stimulated B16 mouse melanoma cells or in vivo in zebrafish and mouse models.

Azathramycin (Desmethyl Azithromycin) is an antibiotic derived from erythromycin, binding to the 50S subunit of the bacterial ribosome, and thus inhibits translation of mRNA.

Imperatorin (8-Isopentenyloxypsoralene) is a modulator of p38, ERK pathway. Imperatorin increases BMP-2 expression (mRNA) and increases bone density volume and mineralization in vivo.

Taurochenodeoxycholic acid sodium (Sodium taurochenodeoxycholate) is one of the main bioactive substances of animals' bile acid. Taurochenodeoxycholic acid sodium induces apoptosis and shows obvious anti-inflammatory and immune regulation properties. It can increase glucose-induced insulin secretion and stimulate the electrical activity of α2-cells and enhance cytosolic Ca(2+) concentration ([Ca(2+)](c)).

TAT 14 acetate, a 14-mer peptide, is an Nrf2 activator with anti-inflammatory properties. TAT 14 acetate increases Nrf2 protein levels due to targeting the Nrf2 binding site on Keap1, but has no effect on Nrf2 mRNA expression.

Abaperidone is a potent 5-HT2A receptor and dopamine D2 receptor antagonist with an IC50 of 6.2 for 5-HT2A receptors and 17 nM for dopamine D2 receptors.Abaperidone is a potentially atypical anti-psychotropic compound that reduces basal hsp70 mRNA expression in rat striatum and prefrontal cortex. expression in the striatum and prefrontal cortex of rats.

safironil is a novel antifibrotic compound and a competitive inhibitor of collagen synthesis. safironil inhibited in vitro experiments on fibroblast activation monitored by collagen I mRNA or smooth muscle alpha-actin levels, and fibrogenesis as judged by type I and type III collagen and laminin production. safironil had no effect on the size of liver granulomas without altering total hydroxyproline, but altered the pattern of fibrosis by increasing type III and decreasing type I collagen deposition.

12R-LOX-IN-2 is an inhibitor of 12R-lipoxygenase (12R-LOX).12R-LOX-IN-2 inhibits imiquimod (IMQ)-induced hyperproliferation of psoriatic keratinocytes and inhibits colony formation.12R-LOX-IN-2 also decreases the protein level of Ki67 and the mRNA expression of IL-17A in IMQ-induced cells. 12R-LOX-IN-2 may be useful in the study of psoriasis and other skin-associated inflammatory diseases.

FT001 is a potent, selective and orally available inhibitor of BET Bromodomain with antitumor activity. FT001 inhibited the expression of MYC with the IC50 value of 0.46 μM). FT001 has potent antiproliferative effects against MV-4-11 and demonstrates significant MYC mRNA suppression both in vitro and in vivo.

CLK1 2-IN-3 (Cpd-3) is a potent and selective CLK1 and CLK2 inhibitor with antiproliferative activity and inhibits the activities of CLK1, CLK2, SRPK1, SRPK2, and SRPK3.CLK1 2-IN-3 induces nuclear speckle enlargement, which induces S6K pre-mRNA-selective splicing and subsequent inhibition of cell growth of multiple cancer cell types. cancer cell types cell growth.

KYN-101 is an orally active and selective aryl hydrocarbon receptor (AHR) inhibitor with anticancer activity. KYN-101 decreases CYP1A1 mRNA expression and can be used in the study of breast cancer and acute myeloid leukemia. KYN-101 is an orally active and selective aryl hydrocarbon receptor (AHR) inhibitor with anticancer activity.

B I09, an IRE-1 RNase inhibitor with an IC50 of 1230 nM, inhibits splicing of XBP1 mRNA in human WaC3 cells and expression of xbp-1 in LPS-stimulated B cells. B I09 can be used to simulate the defects of XBP-1 in CLL cells., an IRE-1 RNase inhibitor with an IC50 of 1230 nM, inhibits splicing of XBP1 mRNA in human WaC3 cells and expression of xbp-1 in LPS-stimulated B cells. B I09 can be used to simulate the defects of XBP-1 in CLL cells., an IRE-1 RNase inhibitor with an IC50 of 1230 nM, inhibits splicing of XBP1 mRNA in human WaC3 cells and expression of xbp-1 in LPS-stimulated B cells. B I09 can be used to simulate the defects of XBP-1 in CLL cells.

Sinefungin (Adenosyl-Ornithine) is an effective inhibitor of virion mRNA(guanine-7-)-methyltransferase, mRNA(nucleoside-2'-)-methyltransferase, and viral multiplication. Sinefungin is a SET7 9 inhibitor and ameliorates renal fibrosis by inhibiting H3K4 methylation.

Diethylnorspermine HCl (N1,N11-Diethylnorspermine tetrahydrochloride) potently induces SSAT (spermidine/spermine N1-acetyltransferase) mRNA and effectively stabilizes SSAT enzyme activity.

FY-21 is a selective LSD1 inhibitor (IC50= 340 nM) that inhibits proliferation and colony formation of leukemia cells, decreases mRNA levels of the transcription factors HOXA9 and MEIS1, and can be used in the study of leukemia.

SMN-C2 is a selective regulator of SMN2 gene splicing, a risdiplam analogue, a selective RNA-binding ligand that regulates pre-mRNA splicing and acts by binding to SMN2 pre-mRNA.SMN-C2 has the potential to be used in the study of spinal muscular atrophy (SMA).

P53R3 is a potent reactivator of p53, effectively restoring sequence-specific DNA binding to several p53 hot spot mutants, namely p53 R175H, p53 R248W, and p53 R273H. This compound exhibits p53-dependent antiproliferative effects with significantly higher specificity compared to PRIMA-1 and promotes the recruitment of both wild-type p53 and p53 M237I to various target gene promoters. Additionally, P53R3 markedly increases the mRNA, total protein, and cell surface expression of death receptor 5 (DR5), demonstrating its utility in cancer research.

CJ-13,610 is an orally active and nonredox-type inhibitor of 5-lipoxygenase (5-LOX). CJ-13,610 inhibits the biosynthesis of leukotriene B4 and regulates the expression of IL-6 mRNA in macrophages.

HTT-D3 is a potent and orally active huntingtin (HTT) splicing modulator that leads to HTT mRNA degradation and reduction of HTT levels. It also reduces p-glycoprotein (P-gp) efflux and holds significant research value in Huntington's disease.

Hinokiflavone, a novel modulator of pre-mRNA splicing activity both in vitro and in cellulo, inhibits the assembly of the spliceosome, particularly blocking the formation of the B complex. Additionally, it acts as a SUMO protease inhibitor by impeding the activity of sentrin-specific protease 1 (SENP1). Hinokiflavone also demonstrates significant cytotoxicity, including the inhibition of MMP-9.

1. Berberrubine chloride (9-Berberoline Chloride) has antitumor activity. 2. Berberrubine has antidiabetic activity. 3. Berberrubine dose-dependently inhibits IL-8 and MCP-1 protein levels in the media and mRNA expression of the cells stimulated with IL-1beta or TNF-alpha.

DIF-3 is a chemical compound that acts by activating GSK-3β to facilitate the degradation of cyclin D1 and c-Myc, resulting in reduced expression levels of these proteins. In addition, DIF-3 inhibits Wnt β-catenin signaling pathway-related proteins in DLD-1 cells. This compound exerts a potent antiproliferative effect on the HeLa human cervical cancer cell line by inducing cyclin D1 degradation and inhibiting cyclin D1 mRNA expression [1].

Polygalacin D shows anti- proliferation, anti-inflammary, and hepatoprotective activities, it can inhibit the expression of lipopolysaccharide (LPS)-induced iNOS and COX-2 protein and mRNA without an appreciable cytotoxic effect on RAW 264.7 macrophages, and can suppress induction by LPS of pro-inflammatory cytokines such as prostaglandin E2 (PGE2).

Platycodin D may stimulate TNF-α synthesis or inhibit degradation of TNF-α mRNA. Platycodin D (10/30 μM) suppresses prostaglandin E2 production in rat peritoneal macrophages stimulated by the protein kinase C activator 12-O-tetradecanoyl phorbol 13-acetate (TPA). Platycodin D and D3 are useful as expectorant agents in the treatment of various airway diseases, they can increase mucin release from rat and hamster tracheal surface epithelial cell culture and also from intact rat trachea upon nebulization.

Cannabigerol is a high affinity α±2-adrenergic receptor agonist, moderate affinity 5-HT1A receptor antagonist, and low affinity CB1 receptor antagonist ; also binds to the CB2 receptor; it can relieve interocular pressure, which may be of benefit in the treatment of glaucoma.

1. ISOGINKGETIN (4',4'''-Dimethylamentoflavone), a compound derived from the leaves of Ginkgo biloba, to up-regulate adiponectin secretion with potency comparable to that of rosiglitazone, a known modulator of adiponectin production. 2. Isoginkgetin has anti-tumor activity, the mechanistic basis is splicing inhibition , thus, pre-mRNA splicing inhibitors may represent a novel avenue for development of new anti-cancer agents.3. Isoginkgetin can inhibit tumor cell invasion by regulating phosphatidylinositol 3-kinase/Akt-dependent matrix metalloproteinase-9 expression. 4. Isoginkgetin (0.3mg/kg ip for 3d) can reduce the level of O2·- in plasma and erythroeyte and sometimes increase the activity of SOD in anoxic rats, the action being stronger than aspirin.

Talabostat (PT100, Val-boroPro) is a potent, nonselective and orally available dipeptidyl peptidase IV (DPP-IV) inhibitor with a Ki of 0.18 nM. Talabostat is a nonselective DPP-IV inhibitor, inhibiting DPP8/9, FAP, DPP2 and some other DASH family enzymes essentially as potently as it inhibits DPP-IV[1]. Talabostat stimulates the immune system by triggering a proinflammatory form of cell death in monocytes and macrophages known as pyroptosis. The inhibition of two serine proteases, DPP8 and DPP9, activates the proprotein form of caspase-1 independent of the inflammasome adaptor ASC[2]. Talabostat competitively inhibits the dipeptidyl peptidase (DPP) activity of FAP and CD26/DPP-IV, and there is a high-affinity interaction with the catalytic site due to the formation of a complex between Ser630/624 and the boron of talabostat[3]. Talabostat can stimulate immune responses against tumors involving both the innate and adaptive branches of the immune system. In WEHI 164 fibrosarcoma and EL4 and A20/2J lymphoma models, PT-100 causes regression and rejection of tumors. The antitumor effect appears to involve tumor-specific CTL and protective immunological memory. Talabostat treatment of WEHI 164-inoculated mice increases mRNA expression of cytokines and chemokines known to promote T-cell priming and chemoattraction of T cells and innate effector cells[3]. Talabostat treated mice show significant less fibrosis and FAP expression is reduced. Upon PT100 treatment, significant differences in the MMP-12, MIP-1α, and MCP-3 mRNA expression levels in the lungs are also observed. Treatment with PT100 in this murine model of pulmonary fibrosis has an anti-fibro-proliferative effect and increases macrophage activation[4]. [1]. Connolly BA, et al. Dipeptide boronic acid inhibitors of dipeptidyl peptidase IV: determinants of potencyand in vivo efficacy and safety. J Med Chem. 2008 Oct 9;51(19):6005-13. [2]. Okondo MC, et al. DPP8 and DPP9 inhibition induces pro-caspase-1-dependent monocyte and macrophage pyroptosis. Nat Chem Biol. 2017 Jan;13(1):46-53. [3]. Adams S, et al. PT-100, a small molecule dipeptidyl peptidase inhibitor, has potent antitumor effects and augments antibody-mediated cytotoxicity via a novel immune mechanism. Cancer Res. 2004 Aug 1;64(15):5471-80. [4]. Egger C, et al. Effects of the fibroblast activation protein inhibitor, PT100, in a murine model of pulmonary fibrosis. Eur J Pharmacol. 2017 Aug 15;809:64-72.

Crocin (Gardenia Yellow) is a water-soluble carotenoid pigment of saffron (Crocus sativus L. ) that has been used as a spice for flavoring and coloring food preparations, and in Chinese traditional medicine as an anodyne or tranquilizer. Crocin suppresses tumor necrosis factor (TNF)alpha-induced apoptosis of pheochromocytoma (PC12) cells by modulating mRNA expressions of Bcl-2 family proteins, which trigger downstream signals culminating in caspase-3 activation followed by cell death. Crocin prevented the activation of nSMase by enhancing the transcription of gamma-glutamylcysteinyl synthase, which contributes to a stable glutathione supply that blocks the activity of nSMase.