target 1

Target 1 has a wide range of applications in life science related research.

(+)-JQ-1 (JQ1) is a BET bromine domain inhibitor that inhibits BRD4 (1 2) (IC50=77 33 nM) with specificity and reversibility. (+)-JQ-1 induces cell autophagy and inhibits cell proliferation.

DL-Mannitol is a osmotic diuretic, it may play a role in reducing off-target 68Ga-PSMA renal uptake

PARP1/2/TNKS1/2-IN-1 is a multi-target inhibitor of PARP-1, PARP-2, TNKS1 and TNKS2.PARP1/2/TNKS1/2-IN-1 has potential anti-tumor activity and induces apoptosis.

AR antagonist 1 is a potent antagonist of the androgen receptor. It binds to E3 ligase ligands with weak binding affinities to VHL protein in the synthesis of PROTAC ARD-266.

MCT1-IN-3 is a monocarboxylate transporter 1 (MCT1) inhibitor. The solute carrier (SLC) monocarboxylate transporter 1 (MCT1; SLC16A1) represents a promising target for the treatment of cancer. MCT1-IN-3 (compound 24) showed the highest MCT1 transport inhibition with an IC50 value of 81.0 Nm. MCT1-IN-3 has also significant inhibitivity against the multidrug transporter ABCB1.

MKC-1 (Ro-31-7453) is an orally bioavailable, small-molecule, bisindolylmaleimide cell cycle inhibitor with potential antineoplastic activity. MKC-1 and its metabolites inhibit tubulin polymerization, blocking the formation of the mitotic spindle, which may result in

BMS-1166-N-piperidine-CO-N-piperazine dihydrochloride is a resorcinol di-Ph ether scaffold-based programmed cell death-1 (PD-1)/programmed cell death ligand 1 (PD-L1) inhibitor that inhibits the PD-1/PD-L1 interaction with an IC50 of 39.2 nM.BMS-1166-N-piperidine-CO-N-piperazine dihydrochloride contains the target protein PD-1/PD-L1 ligand and PROTAC linker.BMS-1166-N-piperidine-CO-N-piperazine dihydrochloride can be used to synthesize PROTAC linker. BMS-1166-N-piperidine-CO-N-piperazine dihydrochloride can be used to synthesize PROTAC PD-1/PD-L1 degrader-1. BMS-1166-N-piperidine-CO-N-piperazine dihydrochloride has anticancer activity. BMS-1166-N-piperidine-CO-N-piperazine dihydrochloride can be used as a diluent for the preparation of tablets for direct compression.

Crebinostat is a potent histone deacetylase (HDAC) inhibitor, inhibiting HDAC1, HDAC2, HDAC3, and HDAC6 with IC50s of 0.7 nM, 1.0 nM, 2.0 nM, and 9.3 nM, respectively.Crebinostat increases the density of synapsin-1 punctae along dendrites in neurons in vitro. Crebinostat increased the density of synapsin-1 punctae along dendrites in neurons in vitro. crebinostat modulated chromatin-mediated neuroplasticity and enhanced memory in mice. crebinostat induced histone H3 and histone H4 acetylation and enhanced the expression of the cAMP-responsive element binding protein (CREB) target gene, Egr1. Crebinostat induces histone H3 and histone H4 acetylation and enhances the expression of Egr1, a cAMP response element binding protein (CREB) target.

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

Triciferol acts as a multiple ligand with combined VDR agonist and HDAC antagonist activities. Triciferol binds directly to the VDR ( IC 50 =87 nM), and functions as an agonist with 1,25D-like potency on several 1,25D target genes. Triciferol induces marked tubulin hyperacetylation, and augments histone acetylation. Triciferol also exhibits efficacious antiproliferative and cytotoxic activities in cancer cell models in vitro [1].

FASN-in-1 is an effective, specific inhibitor of fatty acid synthase (FASN), a compound specifically designed to target and inhibit the activity of the enzyme involved in fatty acid synthesis, potentially disrupting fatty acid production and affecting various cellular processes.

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].

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.

Dactolisib (BEZ235) is an orally bioavailable inhibitor of PI3K and mTOR (IC50s: 4 nM/5 nM/7 nM/75 nM, and 20.7 nM for p110α/p110γ/p110δ/p110β and mTOR).

Mirin is a potent Mre11-Rad50-Nbs1 (MRN) complex inhibitor. Mirin prevents MRN-dependent activation of ATM (IC 50 =12 μM) without affecting ATM protein kinase activity, and it inhibits Mre11-associated exonuclease activity. Consistent with its ability to target the MRN complex, Mirin abolishes the G2/M checkpoint and homology-dependent repair in mammalian cells [1].

Polyphyllin D induces apoptosis via the mitochondrial apoptotic pathway as evidenced by decreased Bcl-2 expression levels, disruption of MMP and increased Bax, cytochrome C, and cleaved-caspase-3 levels. Polyphyllin D has an anti-angiogenic effect. Polyphyllin D has toxicity in human RBCs as well as its underlying mechanism for the hemolysis and eryptosis/erythroptosis. Polyphyllin D has strong anticancer activity, can overcome drug resistance in R-HepG2 cells and elicit programmed cell death via mitochondrial dysfunction.

Torin 1 is an effective inhibitor of mTORC1/2 with (IC50: 2 nM/10 nM); has 1000-fold selectivity for mTOR than PI3K.

WYE-354(IC50=5 nM) is an effective, selective and ATP-competitive mTOR inhibitor. It blocks mTORC2 P-AKT(S473) and mTORC1 P-S6K(T389), not P-AKT(T308). The selectivity for mTOR is higher than PI3Kα (>100-fold) and PI3Kγ (>500-fold).

ERK-IN-2, an ERK2 inhibitor, exhibits an IC50 value of 1.8 nM. At doses greater than 10 μM, it may induce off-target toxicity and/or activity [1].

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)

MC-VC-PABC-C6-alpha-Amanitin is an antibody-drug conjugate that combines the anticancer toxin alpha-Amanitin with the monoclonal antibody MC-VC-PABC-C6. Alpha-Amanitin acts as a potent inhibitor of RNA polymerase IIα, enabling the conjugate to selectively target and recognize HER2-positive tumor cells. This specificity makes MC-VC-PABC-C6-alpha-Amanitin a valuable research tool in the study of breast and gastric cancers [1].

Quazomotide, a class II peptide epitope of WT1 with the sequence RSDELVRHHNMHQRNMTKL, elicits a peptide-specific CD4(+) response to target WT1(+) tumor cells. It serves both as an immunological agent for active immunization and as an antineoplastic agent [1] [2].

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.

Ormutivimab (rhRIG), a recombinant human monoclonal antibody designed to target the rabies virus, effectively neutralizes various strains and demonstrates strong efficacy as a post-exposure prophylaxis (PEP) treatment in model studies [1] [2].

PTD2 (Ac-Gly-Val-Nle-Arg-Ile-NH2) serves as a potent and selective WHSC1 inhibitor, exhibiting micromolar affinity for this target [1].

Etigilimab (OMP-313M32), a humanized IgG1 monoclonal antibody, inhibits TIGIT from interacting with PVR (CD155; poliovirus receptor) and suppresses subsequent signaling, resulting in target cell death [1].

Activated C Subunit is utilized in synthesizing exon jumping oligomer conjugates that complement specific target sites within the human anti-muscular atrophy protein gene to promote exon 51 skipping, offering a research avenue for muscular dystrophy [1].

TCRS-417 (T417), a small molecule compound, selectively binds to the interface between PBX1 and its specific DNA target sequence, disrupting the PBX1-DNA interaction. This compound has potential research applications in cancer, developmental, inflammatory, autoimmune, and neurodegenerative diseases [1].

SAR441255 is a potent unimolecular peptide that acts as a GLP-1/GIP/GCG receptor triagonist, demonstrating balanced activation across all three target receptors. It has shown positive acute glucoregulatory effects in diabetic obese monkeys [1].

PROTAC EGFR degrader 4 is a potent molecule designed to target and degrade mutant EGFR, showcasing its effectiveness by inducing degradation of EGFR del19 and EGFR L858R/T790M with DC50 values of 0.51 nM and 126 nM, respectively. Furthermore, it significantly inhibits the growth of HCC827 and H1975 cell lines, demonstrating IC50 values of 0.83 nM and 203.1 nM, respectively. The induced degradation of EGFR by this compound is associated with autophagy [1].

Romilkimab (SAR156597) is a chimeric humanized immunoglobulin (Ig) antibody designed to specifically target interleukins 4 and 13 (IL-4 and IL-13) [1].

Activated EG3 Tail facilitates the synthesis of exon-skipping oligomer conjugates that target specific sites within the human anti-muscular atrophy protein gene, promoting exon 51 skipping. This compound holds potential for research into muscular dystrophy treatments [1].

Syk-IN-4 is a potent, selective, and orally bioavailable inhibitor of SYK, demonstrating an IC50 of 0.31 nM. It targets SYK, which has been identified as a potential therapeutic target for autoimmunity and hematological cancers[1].

Anticancer agent 126 (compound 12), a WDR5 inhibitor, exhibits anticancer properties by disrupting the WDR5-MYC interaction in cells, subsequently reducing MYC target gene expression [1].

α-Hemolysin (Staphylococcus aureus), a polypeptide virulence factor of Staphylococcus aureus, disrupts host cell plasma membranes. Upon binding to the cell surface, its monomers create a homoheptamic prepore, which evolves into a mature transmembrane pore, facilitating K+ and Ca2+ ion transport that induces necrotic death in target cells [1].

AP-III-a4 hydrochloride (ENOblock hydrochloride) is a novel small molecule which is the first, nonsubstrate analogue that directly binds to enolase and inhibits its activity (IC50=0.576 uM); inhibit cancer cell metastasis in vivo. IC50 value: 0.576 uM [1]

BNM-III-170 is able to inhibit HIV-1 viral entry into target cells.

Antagonist of 14.3.3 proteins (KD ≈80 nM). Competitively inhibits 14.3.3-ligand interactions without requiring phosphorylation. Blocks the ability of 14.3.3 to bind to target proteins such as Raf-1, Bad, ASK1 and exoenzyme S.

Ipatasertib-NH2 (GDC-0068-NH2;RG7440-NH2) is a ligand for target protein AKT for PROTAC, binds to lenalidomide, a ligand of ubiquitin E3 ligase cereblon (CRBN), via a ten-hydrocarbon linker to form INY-03-041 to degrade AKT[1].

Biperiden Hydrochloride (KL 373 Hydrochloride) is an antiparkinsonian agent, which is the selective central M1 cholinoreceptors blocker and it is used for the adjunctive treatment of all forms of Parkinson's disease (postencephalitic, idiopathic, and arte

SIC5-6 is a potent inhibitor of Separase, a substantial cysteine protease implicated in critical cellular processes such as chromosome segregation during mitosis and meiosis, DNA damage repair, centrosome disengagement and duplication, as well as spindle stabilization and elongation. Given its overexpression in many solid cancers, Separase presents an attractive target for chemotherapy [1].

Lenzilumab (KB 003) is a humanized monoclonal antibody designed to target CSF2/GM-CSF, with applications in COVID-19 and studies on chronic myelomonocytic leukemia (CMML) and juvenile myelomonocytic leukemia (JMML) [1] [2].

Mal-amido-PEG12-NHS ester is a polyethylene glycol (PEG)-derived linker for proteolysis-targeting chimeras (PROTACs)[1]. It is employed in the synthesis of PROTACs, enabling the conjugation of desired target-specific ligands for protein degradation[1].

Isoguaiacin, a natural product [1], exhibits (hass) the potential to be (to exist as) an (a) effective pharmacological agent due to its (its) ability to inhibit (the inhibition of) mushroom tyrosinase. This (The) inhibition is (taking place) in a manner that demonstrates greater (a higher) selectivity towards mushroom tyrosinase compared to human tyrosinase, suggesting a reduced (a lower) risk of off-target effects in humans. Additionally, isoguaiacin shows (displays) promising (promising) activity against (in combating) certain cancer cell lines, further affirming its potential as (an) anticancer agent.

Angoline hydrochloride, a selective inhibitor of the IL6/STAT3 signaling pathway, demonstrates potent activity with an IC50 value of 11.56 μM. It effectively inhibits STAT3 phosphorylation and the expression of its target genes, subsequently reducing cancer cell proliferation [1].

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. AS-99 TFA blocks cell proliferation, induces apoptosis and differentiation, downregulates MLL fusion target genes, and reduces the leukemia burden in vivo[1]. AS-99 TFA is tested against a panel of 20 histone methyltransferases, including NSD1, NSD2, NSD3, and SETD2. NO significant inhibition is observed at 50 μM of AS-99 TFA on any of the tested histone methyltransferases, indicating over 100-fold selectivity towards ASH1L[1].AS-99 TFA shows effect on the growth of the MLL leukemia cells (MV4;11, MOLM13, KOPN8, RS4;11) with the GI50 values ranging from 1.8 μM to 3.6 μM[1].AS-99 (1-8 μM; 7 days) TFA also induces apoptosis in the MLL leukemia cells, but not in the K562 cells, as assessed by the quantification of the Annexin V positive cells[1].AS-99 TFA suppresses MLL fusion driven transcriptional programs[1]. AS-99 (30 mg/kg; i.p.; q.d., treated for 14 consecutive days) TFA reduces leukemia burden in mice[1].AS-99 TFA is used for in vivo studies in mice, which reveals favorable exposure in plasma upon i.v. and i.p. administration (AUC = 9701 hr* ng/mL and 10,699 hr* ng/mL, respectively), suitable half-life (~5-6 h) and Cmax >10 μM[1]. [1]. David S. Rogawski, Jing Deng, Hao Li, Tomasz Cierpicki, Jolanta Grembecka, et al. Discovery of first-in-class inhibitors of ASH1L histone methyltransferase with anti-leukemic activity. Nat Commun. 2021 May 14;12(1):2792.

Cofetuzumab (PF-06523435) is a humanized IgG1-κ monoclonal antibody designed to target PTK7, with Chinese Hamster Ovary (CHO) cells acting as the primary expression system [1].

PROTAC TTK degrader-1, a potent threonine tyrosine kinase (TTK) PROTAC degrader, demonstrates DC50 values of 1.7 nM in COLO-205 cells and 5.8 nM in HCT-116 cells, indicating effective target degradation. Furthermore, it shows anticancer efficacy in a xenograft mouse model with COLO-205 human colorectal cancer cells [1].

Activated T Subunit is employed in synthesizing exon-jumping oligomer conjugates that target specific sites within the human anti-muscular atrophy protein gene to induce exon 51 skipping, a potential avenue for muscular dystrophy research [1].