target 5

Target 5 has a wide range of applications in life science related research.

WAY-600 is a potent, ATP-competitive, and selective inhibitor of mTOR with an IC50 of 9 nM; it blocks mTORC1 P-S6K(T389) and mTORC2 P-AKT(S473) but not P-AKT(T308), and is selective for mTOR over PI3Kα (>100-fold) and PI3Kγ (>500-fold).

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.

Liothyronine Sodium is the sodium salt form of liothyronine, a synthetic form of the levorotatory isomer of the naturally occurring thyroid hormone triiodothyronine (T3). Liothyronine sodium (3,3',5-Triiodo-L-thyronine sodium) binds to nuclear thyroid receptors which then bind to thyroid hormone response elements of target genes. As a result, liothyronine sodium induces gene expression that is required for normal growth and development. Liothyronine sodium is more potent and has a more rapid action than thyroxine (T4).

5-fluorouridine is also known as FUrd, 5-Fluorouracil 1-beta-D-ribofuranoside, 5-Fur, or 5-Fluoro-uridine. 5-fluorouridine is a solid. This compound belongs to the pyrimidine nucleosides and analogues. These are compounds comprising a pyrimidine base attached to a sugar. 5-fluorouridine is known to target uridine phosphorylase. FUrd is often used in chemical and biochemical comparison studies with fluorouracil and thymine analogs.

5-Methyluridine (Thymine riboside) is an endogenous methylated nucleoside found in human fluids; methylated purine bases are present in higher amounts in tumor-bearing patients compared to healthy controls.DNA hypermethylation is a common finding in malignant cells and has been explored as a therapeutic target for hypomethylating agents.

D-α-Hydroxyglutaric acid disodium [Disodium (R)-2-Hydroxyglutarate] is a competitive inhibitor of α-ketoglutarate-dependent dioxygenases with a Ki of 0.628 mM.

Sarpogrelate hydrochloride (MCI-9042) , a selective 5-HT2 antagonist, has been widely used as an anti-platelet agent for the treatment of PAD. Target: 5-HT2 Recepter Sarpogrelate is a drug which acts as an antagonist at the 5HT2A and 5-HT2B receptors. Sarpogrelate hydrochloride was shown to have the same affinity as ritanserin for 5-HT2A receptors, with a Ki value of 8.39 nM. Sarpogrelate hydrochloride lacked prominent 5-HT1-like, 5-HT3, beta, H1, H2 and M3 antagonist activity and weakly blocked alpha 1-adrenoceptors (pKB = 6.30). (S)-M-1 showed weak affinity for 5-HT1-like receptors (pKB = 6.30), alpha 1- (pKB = 6.80) and beta- (pKB = 6.54) adrenoceptors, while (R)-M-1 was a weak antagonist at histamine H1 receptors (pKB = 6.49). After 12 weeks of sarpogrelate administration, FBF and LBF responses during RH showed significant increases from 13.2 + - 1.7 to 18.1 + - 2.2 mL min per 100 mL tissue (P < 0.01) and from 8.2 + - 0.9 to 14.2 + - 2.1 mL min per 100 mL tissue (P < 0.05), respectively. Sarpogrelate hydrochloride -induced augmentation of FBF and LBF responses to RH was maintained at 24 weeks. Long-term oral administration of sarpogrelate improves vascular function in patients with PAD.

Thymine is one of the four bases of DNA and is able to act as a target for 5-fluorouracil in animal cancer models with Km=2.3 μM.

2'-Deoxyguanosine 5'-monophosphate disodium (5'-dGMP disodium) is a GTP derivative that serves as an oxidizable target and is used in forming polycomplexes with other compounds.

5-Aminouridine (4-Chloro-2-isopropyl-5-methylphenol(chlorothymol)) modifies nucleobases and is incorporated into the target DNA. 5-Aminouridine inhibits the growth of tumors, viruses, and fungi.

SB 242084 hydrochloride is a 5-HT2C receptor antagonist(pKi=9.0) that displays 158- and 100-fold selectivity over 5-HT2A and 5-HT2B receptors respectively.IC50 value: 9.0(pKi) [1]Target: 5-HT2C antagonistin vitro: SB 242084 had over 100-fold selectivity over a range of other 5-HT, dopamine and adrenergic receptors. In studies of 5-HT-stimulated phosphatidylinositol hydrolysis using SH-SY5Y cells stably expressing the cloned human 5-HT2C receptor, SB 242084 acted as an antagonist with a pKb of 9.3, which closely resembled its corresponding receptor binding affinity [1].in vivo: SB 242084 potently inhibited m-chlorophenylpiperazine (mCPP, 7 mgkg i.p. 20 min pre-test)-induced hypolocomotion in rats, a model of in vivo central 5-HT2C receptor function, with an ID50 of 0.11 mg kg i.p., and 2.0 mg kg p.o. SB 242084 (0.1-1 mg kg i.p.) exhibited an anxiolytic-like profile in the rat social interaction test, increasing time spent in social interaction, but having no effect on locomotion. SB 242084 (0.1-1 mg kg i.p.) also markedly increased punished responding in a rat Geller-Seifter conflict test of anxiety, but had no consistent effect on unpunished responding [1].

WHI-P97 is a rationally designed potent inhibitor of JAK-3. IC50 value: Target: JAK3 Treatment of mast cells with WHI-P97 inhibited the translocation of 5-lipoxygenase (5-LO) from the nucleoplasm to the nuclear membrane and consequently 5-LO-dependent leukotriene (LT) synthesis after IgE receptor/FcepsilonRI crosslinking by >90% at low micromolar concentrations. WHI-P97 did not directly inhibit the enzymatic activity of 5-LO, but prevented its translocation to the nuclear membrane without affecting the requisite calcium signal.

Diflapolin is a highly active dual 5-lipoxygenase-activating protein (FLAP) and soluble epoxide hydrolase (sEH) inhibitor, exhibiting marked anti-inflammatory efficacy and high target selectivity.

Thalidomide 5'-amine-alkylC6-amine serves as a specialized cereblon ligand for PROTAC research and development, combining an E3 ligase ligand and an alkylC6 linker with a terminal amine for target protein ligand conjugation. It is among a series of functionalized tool molecules designed for PROTAC R&D.

Functionalized von-Hippel-Lindau protein ligand (VHL) for PROTAC research and development; incorporates an E3 ligase ligand plus alkylC4 linker with terminal carboxylic acid ready for conjugation to a target protein ligand. Part of a range of functionalized tool molecules for PROTAC R&D. This product has been recently renamed. The previous name for this product was VH 032 - linker 5 PROTAC is a registered trademark of Arvinas Operations, Inc., and is used under license.

LYP-IN-1 is a powerful LYP inhibitor that demonstrates high potency, selectivity, and specificity, with a Ki of 110 nM and an IC 50 of 0.259 μM. Beyond its primary target, LYP-IN-1 also exhibits selectivity towards a wide range of PTPs, including SHP1 (IC 50 = 5 μM) and SHP2 (IC 50 = 2.5 μM). Additionally, LYP-IN-1 demonstrates remarkable efficacy in T- and mast cells, making it a valuable tool for investigating autoimmune disorders.

UCSF678 is a 42 nM arrestin-biased partial agonist at the 5-HT5AR with a more restricted off-target profile and decreased assay liabilities compared to the commercial antagonist SB-699551. UCSF678 is a selective probe for studying the function of the 5-HT5AR [1].

Lipid-derived lipoxins are produced at the site of vascular and mucosal inflammation where they down-regulate polymorphonuclear leukocyte recruitment and function. 15(R)-Lipoxin A4 (15(R)-LXA4) is derived from the aspirin-triggered formation of 15(R)-HETE from arachidonic acid. [1] [2] 15(R)-LXA4 inhibits LTB4-induced chemotaxis, adherence, and transmigration of neutrophils with twice the potency of LXA4 demonstrating activity in the nM range.[2] [3] The anti-inflammatory effects of aspirin may be ascribed in part to the ability of 15(R)-LXA4 to regulate leukocyte function.[4] 15(R)-LXA4 is reported to promote resolution of inflammation in LPS-treated stromal cells derived from intermediate-stage diseased supraspinatus tendons as evidenced by increased expression of the STAT-6 pathway target genes, ALOX15 and CD206.[5]

MK-8245 trifluoroacetate is a phenoxy piperidine isoxazole derivative functioning as a potent, liver-targeting stearoyl-CoA desaturase (SCD) inhibitor, demonstrating significant anti-diabetic and anti-dyslipidemic effects. It showcases high specificity and efficacy against SCD1 across various species, with IC50 values of 1 nM for human SCD1 and 3 nM for both rat and mouse SCD1. MK-8245's mechanism includes a tetrazole acetic acid moiety that facilitates liver-targeting through OATPs recognition. Its inhibition potency in rat hepatocyte assays (IC50 of 68 nM) surpasses that in HepG2 cell assays devoid of active OATPs (IC50 of ~1 μM), highlighting its liver specificity. Moreover, MK-8245 exhibits over 100,000-fold selectivity against Δ-5 and Δ-6 desaturases in comparative assays. In vivo studies reveal MK-8245's preferential liver distribution in mice, rats, dogs, and rhesus monkeys, underscoring its potential for minimizing adverse effects in non-target tissues. Additionally, its administration in eDIO mice before glucose challenges significantly improves glucose clearance, indicating its therapeutic promise in diabetes management.

NHC-triphosphate triammonium is an active phosphorylated intracellular metabolite of β-d-N4-Hydroxycytidine (NHC) as a triphosphate form[1]. NHC-triphosphate triammonium is a weak alternative substrate for the viral polymerase and can be incorporated into HCV replicon RNA[1][2]. In an intracellular metabolism assay, HCV replicon cells are treated with 10 μM 3H-labeled NHC, and intracellular nucleotide levels are determined after 1, 2 and 8 hours incubations. NHC is rapidly convered into the mono-, di-, and triphosphate forms, and NHC-TP reaches up to 71.12 pM after 8 hours[1].NHC-triphosphate triammonium (NHC-TP) (5-40 μM) absence leads to full-length polymerization products, it can be a weak alternative substrate. In addition, incorporation of NHC-TP instead of CTP increases the molecular weight of the polymerization product by 16 (one extra oxygen) for each event and an obvious electrophoretic shift is observed in cell-free HCV NS5B polymerization reactions[1].Huh-7 cells are incubated with (10-50 μM; 4 h) NHC or a McGuigan phosphoramidate prodrug of NHC. Intracellular levels of the parental compounds and phosphorylated metabolites are measured using LC-MS/MS. Small amounts of NHC-monophosphate (MP) and NHC-diphosphate (DP) can be observed, while NHC-triphosphate triammonium remains the most abundant metabolite[2].NHC-triphosphate triammonium (NHC-TP) metabolite may directly target the viral polymerase and behave as a nonobligate chain terminator. It plays a prominent role in inhibiting early negative-strand RNA synthesis, either through chain termination or mutagenesis, which may in turn interfere with correct replicase complex formation. [1]. Stuyver LJ,et al. Ribonucleoside analogue that blocks replication of bovine viral diarrhea and hepatitis C viruses in culture.Antimicrob Agents Chemother. 2003 Jan;47(1):244-54. [2]. Maryam Ehteshami, et al. Characterization of β-d- N4-Hydroxycytidine as a Novel Inhibitor of Chikungunya Virus.

Adenosine 5’-methylenediphosphate is an inhibitor of ecto-5’-nucleotidase, also known as CD73, with a Kivalue of 37 nM.1It inhibits cAMP accumulation induced by adenosine 5’-monophosphate , adenosine 5’-diphosphate , or adenosine 5’-triphosphate but not adenosine in VA-13 human fibroblasts when used at a concentration of 100 μM. Adenosine 5’-methylenediphosphate reduces proliferation of U138MG glioma cells, as well as inhibits the invasion and migration of MHCC97H hepatocellular carcinoma (HCC) cells in a migration assay.2,3It increases tumor infiltration of CD3+CD8+T cells and reduces tumor growth in a K1735 murine melanoma model when administered at a dose of 400 μg/mouse.4 1.Bruns, R.F.Adenosine receptor activation by adenine nucleotides requires conversion of the nucleotides to adenosineNaunyn Schmiedebergs Arch. Pharmacol.315(1)5-13(1980) 2.Braganhol, E., Tamajusuku, A.S.K., Bernardi, A., et al.Ecto-5′-nucleotidase/CD73 inhibition by quercetin in the human U138MG glioma cell lineBiochim. Biophys. Acta1770(9)1352-1359(2007) 3.Shali, S., Yu, J., Zhang, X., et al.Ecto\5′\nucleotidase (CD73) is a potential target of hepatocellular carcinomaJ. Cell Physiol.234(7)10248-10259(2018) 4.Forte, G., Sorrentino, R., Montinaro, A., et al.Inhibition of CD73 improves B cell-mediated anti-tumor immunity in a mouse model of melanomaJ. Immunol.189(5)2226-2233(2021)

Bimiralisib (PI3K-IN-2) is an orally bioavailable pan inhibitor of PI3K and inhibitor of the mTOR, with potential antineoplastic activity. PI3K-IN-2 inhibits the PI3K kinase isoforms alpha, beta, gamma and delta and, to a lesser extent, mTOR kinase, which may result in tumor cell apoptosis and growth inhibition in cells overexpressing PI3K/mTOR. Activation of the PI3K/mTOR pathway promotes cell growth, survival, and resistance to both chemotherapy and radiotherapy.

Quorum sensing is a regulatory system used by bacteria for controlling gene expression in response to increasing cell density. Controlling bacterial infections by quenching their quorum sensing systems is a promising field of study. The expression of specific target genes, such as transcriptional regulators belonging to the LuxIR family of proteins, is coordinated by the synthesis of diffusible acylhomoserine lactone (AHL) molecules. N-3-oxo-tetradecanoyl-L-homoserine lactone (3-oxo-C14-HSL) is a small diffusible signaling molecule involved in quorum sensing, thereby controlling gene expression and affecting cellular metabolism in bacteria.[1] [2] [3] It appears later than shorter acyl chain AHLs in developing biofilms [4] and, like other long chain 3-oxo-AHLs, stimulates the production of putisolvin, [5] which in turn, inhibits biofilm formation.

XJB-5-131 is a synthetic, bi-functional antioxidant specifically designed to target mitochondria for the scavenging of reactive oxygen species (ROS) and electrons, thereby acting as a radical scavenger. Additionally, it serves as an effective protector and mitigator against ionizing irradiation for cord blood mononuclear cells (CB MNCs).

PRMT5-IN-22 (compound 53), an inhibitor of protein arginine methyltransferase 5 (PRMT5), exhibits anti-tumor activity. As a protein arginine methyltransferase, PRMT5 represents a novel anti-tumor target associated with epigenetic modification [1].

CBB1007 trihydrochloride is a cell-permeable amidino-guanidinium compound that acts as a potent, reversible and substrate competitive LSD1 selective inhibitor (IC50 = 5.27 μM for hLSD1). IC50 Value: 5.27 uM Target: hLSD1 CBB1007 efficiently can block LSD1-mediated demethylation of H3K4Me2 and H3K4Me (IC50 ≤ 5 μM) with no effect on H3K4Me3 and H3K9Me2, and LSD2 and JARID1A activities. Increases H3K4Me2 and H3K4Me contents (IC50 ≤ 5 μM), and causes activation of epigenetically suppressed CHRM4/M4-ArchR and SCN3A genes in F9 cells (IC50 ≤ 3.74 μM). CBB1007 was Shown to preferentially arrest the growth of pluripotent tumors with minimal effect on non-pluripotent cancer or normal somatic cells (IC50 ≥ 100 μM).

YW3-56 is a potent peptidylarginine deiminase (PAD) inhibitor, with an IC50 of 1-5 μM for PAD4. Compared with Cl-amidine, YW3-56 shows >60-fold increase in cell growth inhibition efficacy (IC50 about 2.5 μM) but only 5-fold increase in PAD4 inhibition (IC sub>50 about 1-5 μM). At 2-4 μM concentrations, YW3-56 displays mainly cytostatic effects by slowing cell division, whereas at higher concentrations, it exerts cytotoxic effects by altering cell morphology and killing cells[1]. [1]. Wang Y, et al. Anticancer peptidylarginine deiminase (PAD) inhibitors regulate the autophagy flux and t he mammalian target of rapamycin complex 1 activity. J Biol Chem. 2012 Jul 27;287(31):25941-53.

PQR626 is a rapamycin derivative that acts as a highly potent, selective, orally active, and brain-penetrant mTOR inhibitor. It exhibits remarkable inhibitory effects on the mammalian target of the rapamycin (mTOR) pathway, with an IC50 value of 5 nM and a Ki value of 3.6 nM. This compound, PQR626, holds promise for advancing research in the field of neurological disorders.

Thalidomide-5-NH-PEG1-NH2 hydrochloride is a Thalidomide-based cereblon ligand designed for CRBN protein recruitment. It facilitates the formation of PROTAC molecules by linking to target protein ligands, such as THAL-SNS-032, via a connector.

Reslizumab is humanized monoclonal antibodies that target interleukin-5 (IL-5) for the treatment of eosinophilic asthma.

DL-5-Hydroxylysine hydrochloride (5-hydroxylysine hydrochloride) is a racemic mixture of D- and L- enantiomers of 5-hydroxylysine which may be used as potential target markers for radical-induced protein oxidation.

JPC0323 is a dual positive allosteric modulator of the 5-HT2C and 5-HT2A receptors, featuring on-target properties, acceptable plasma exposure, and adequate brain penetration. It is utilized in research pertaining to neurological diseases [1].

Aldose reductase-IN-3 (Compound 5) is an effective and moderately selective aldose reductase (AR) inhibitor (IC50=3.99 μM) with research potential in sepsis, a molecular target involved in various inflammatory diseases (including sepsis).

Antiviral agent 5 is a crucial intermediate utilized in the development of antiviral agents that specifically target 3C and 3CL proteases, which includes the SARS-CoV-2 M pro enzyme.

PKI-179 is a potent, orally active compound that functions as a dual PI3K mTOR inhibitor. It demonstrates IC50 values of 8 nM for PI3K-α, 24 nM for PI3K-β, 74 nM for PI3K-γ, 77 nM for PI3K-δ, and 0.42 nM for mTOR. Additionally, it is effective against E545K and H1047R mutations, with IC50s of 14 nM and 11 nM, respectively. In vivo studies have shown that PKI-179 possesses anti-tumor capabilities[1][2].

YW3-56 is an inhibitor of protein arginine deiminase 2 (PAD2) and PAD4 (IC50s = 0.5-1 and 1-5 μM, respectively).1It inhibits the growth of U2OS osteosarcoma cells (IC50= ~2.5 μM) in a p53-dependent mannerviainduction of SESN2 and subsequent inhibition of mTORC1. YW3-56 (10 mg/kg) reduces tumor growth in an S-180 murine sarcoma tumor model. It also inhibits tumor growth in the 1883 MDA-MB-231 breast cancer bone metastasis mouse xenograft model.2 1.Wang, Y., Li, P., Wang, S., et al.Anticancer peptidylarginine deiminase (PAD) inhibitors regulate the autophagy flux and the mammalian target of rapamycin complex 1 activityThe Journal of Biological Chemisty287(31)25941-25952(2012) 2.Wang, S., Chen, X.A., Hu, J., et al.ATF4 gene network mediates cellular response to the anticancer PAD inhibitor YW3-56 in triple-negative breast cancer cellsMol. Cancer Ther.14(4)877-888(2015)

Icapamespib, also known as PU-HZ 151, is a heat shock protein 90 (HSP90) inhibitor. PU-HZ151 showed EC50 of 5 nM in the FP assay as compared to 11 nM for PU-H71 and a logD of 2.37 as compared to 1.21 for PU-H71. PU-HZ151 and radiolabeled PU-HZ151 showed selectivity for epichaperomes over the individual chaperome members. Icapamespib demonstrated the ability to productively engage the target in cells, mice, and humans.

AS-99 is a first-in-class, potent, and selective ASH1L histone methyltransferase inhibitor (IC50= 0.79 μM, Kd= 0.89 μM) with anti-leukemic activity, blocking cell proliferation, inducing apoptosis and differentiation, downregulating MLL fusion target genes, and reducing the leukemia burden in vivo[1].

TLS-IN-5, also known as Rev1-IN-5, is the first small molecule inhibitor of translesion synthesis (TLS) that target Rev1-CT.

AS-99 TFA is a first-in-class, potent, and selective ASH1L histone methyltransferase inhibitor (IC50= 0.79 μM, Kd= 0.89 μM) with anti-leukemic activity. It blocks cell proliferation, induces apoptosis and differentiation, downregulates MLL fusion target genes, and reduces the leukemia burden in vivo[1].

AZD7687 is a potent and selective DGAT1 inhibitor with an IC50 value of 80 nM (hDGAT1). IC50 value: 80 nM [1] Target: DGAT1 in vitro: Plasma AZD7687 exposure was measured repeatedly. AZD7687 markedly reduced postprandial TAG excursion with a steep concent

MRTX9768 hydrochloride is a potent, orally active PRMT5 inhibitor. MRTX9768 hydrochloride is a synthetic lethal-based inhibitor binding the PRMT5-MTA complex[1]. MRTX9768 inhibits SDMA and cell proliferation in HCT116 MTAP-del cells (SDMA IC50 3 nM; prolif. IC50 11 nM) with marked selectivity over HCT116 MTAP-WT cells (SDMA IC50 544 nM; prolif. IC50 861 nM)[1].MRTX9768 selectively targets MTAP CDKN2A-deleted tumors[2][1]. In xenograft studies, oral administration of MRTX9768 demonstrates dose-dependent inhibition of SDMA in MTAP-del tumors, with less SDMA modulation observed in bone marrow[1]. [1]. Christopher R. Smith, et al. Abstract LB003: Fragment based discovery of MRTX9768, a synthetic lethal-based inhibitor designed to bind the PRMT5-MTA complex and selectively target MTAP CDKN2A-deleted tumors. AACR Annual Meeting 2021; April 10-15, 2021 and May 17-21, 2021; Philadelphia, PA.[2]. Yingqing Chen, et al. Targeting protein arginine methyltransferase 5 in cancers: Roles, inhibitors and mechanisms. Biomed Pharmacother. 2021 Oct 4;144:112252.

Thalidomide-5-NH-PEG3-NH2 hydrochloride is a cereblon ligand based on Thalidomide that targets CRBN proteins. It utilizes a linker to attach to a target protein ligand, facilitating the formation of a PROTAC molecule, such as THAL-SNS-032.

Relamorelin (RM-131) acetate is a pentapeptide ghrelin analog that acts as a selective agonist for the ghrelin growth hormone secretagogue receptor (GHSR). It exhibits a high affinity for the GHS-1a receptor, with a Ki value of 0.42 nM. Notably, Relamorelin acetate can cross the blood-brain barrier and target the central nervous system. This compound effectively increases growth hormone levels and promotes faster gastric emptying. Due to these properties, Relamorelin acetate holds promise for its potential applications in research related to cachexia, gastroparesis, and gastric intestinal dysmobility disorders [4] [5].

PRMT5-IN-23 (compound 50), an inhibitor of protein arginine methyltransferase 5 (PRMT5), exhibits anti-tumor activity. As a novel anti-tumor target associated with epigenetic modification, PRMT5 belongs to the protein arginine methyltransferase family [1].

Pozelimab (REGN3918), a fully human IgG4 monoclonal antibody, is designed to target and bind with high affinity to both C5 and its variants, effectively inhibiting complement-mediated hemolysis. It holds potential for research into complement-mediated diseases [1].

FGFR1 Inhibitor 7 (compound 5), a potent FGFR1 tyrosine kinase inhibitor, exhibits an IC50 of 0.33 nM against its target and demonstrates broad-spectrum cytotoxicity against human cancer cell lines. Additionally, it inhibits MOLT3 cells with an IC50 of 2.1 μM [1].