on-target

Acalabrutinib (ACP-196), also known as ACP-196, is an orally available inhibitor of Bruton's tyrosine kinase (BTK) with potential antineoplastic activity. Upon administration, ACP-196 inhibits the activity of BTK and prevents the activation of the B-cell antigen receptor (BCR) signaling pathway. This prevents both B-cell activation and BTK-mediated activation of downstream survival pathways. This leads to an inhibition of the growth of malignant B cells that overexpress BTK. BTK, a member of the src-related BTK/Tec family of cytoplasmic tyrosine kinases, is overexpressed in B-cell malignancies; it plays an important role in B lymphocyte development, activation, signaling, proliferation and survival.

Lenvatinib (E7080) is a multi-target receptor tyrosine kinase inhibitor that inhibits VEGFR1-3, FGFR1-4, KIT, PDGFR, and RET, and has oral activity. Lenvatinib has the strongest inhibitory activity on VEGFR2 and VEGFR3 (IC50=4/5.2 nM). Lenvatinib has strong anti-tumor activity.

5-HT1A modulator 1 is a small molecule modulator, a high-affinity multi-target ligand with potent inhibitory activity against 5-HT1A receptor (IC50=2 nM), α1-adrenergic receptor (IC50=10 nM), and dopamine D2 receptor (IC50=40 nM). This compound is primarily used for research on neuropsychiatric disorders such as anxiety, depression, or schizophrenia.

JNK-IN-8 (JNK Inhibitor XVI) is an effective JNK inhibitor that inhibits JNK1, JNK2, and JNK3 with IC₅₀ values of 4.7, 18.7, and 1 nM, respectively. JNK-IN-8 offers the advantages of minimal off-target activity, sustained inhibition, and high specificity. JNK-IN-8 primarily acts by blocking the JNK/c-Jun signaling pathway, inhibiting the phosphorylation of the downstream transcription factor c-Jun, thereby regulating the expression of genes associated with inflammatory responses, apoptosis, and stress responses. JNK-IN-8 can be used in research on tumors, inflammation, and neurological diseases.

Carboxy-pyridostatin is a carboxyl-modified derivative of pyridostatin, a classic G-quadruplex ligand, capable of selectively binding to and stabilizing G-quadruplex structures, thereby influencing the DNA conformation in regions related to telomeres and gene regulation. Carboxy-pyridostatin exhibits high molecular specificity for RNA on DNA G4s and can downregulate the ATF-5 protein. Carboxy-pyridostatin inhibits cell proliferation and impedes the formation of stress granules (SGs).

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].

5-Fluorouridine is a metabolite of 5-fluorouracil that inhibits rRNA synthesis in human colon cancer cells and exhibits antitumor and antiviral activity. 5-Fluorouridine exerts a cytotoxic effect on the growth of L1210 cells, with an IC₅₀ value of 2 nM. 5-Fluorouridine binds to poly-A RNA and exhibits antiproliferative activity. 5-Fluorouridine can be used in studies of nucleic acid metabolism, cancer chemotherapy, and viral replication mechanisms.

Apramycin(Nebramycin II) is an aminoglycoside antibiotic used in veterinary medicine. IC50 value:Target: Apramycin stands out among aminoglycosides for its mechanism of action which is based on blocking translocation and its ability to bind also to the eukaryotic decoding site despite differences in key residues required for apramycin recognition by the bacterial target. The drug binds in the deep groove of the RNA which forms a continuously stacked helix comprising non-canonical C.A and G.A base pairs and a bulged-out adenine. The binding mode of apramycin at the human decoding-site RNA is distinct from aminoglycoside recognition of the bacterial target, suggesting a molecular basis for the actions of apramycin in eukaryotes and bacteria. [1]. Apramycin, From Wikipedia

SR 1903 is an inverse agonist of RORγ and PPARγ (IC₅₀ = 100 nM and 209 nM, respectively) and an agonist of LXR (EC₅₀ = 154 nM). It exerts anti-inflammatory and anti-diabetic effects in mouse models of collagen-induced arthritis and diet-induced obesity.

CDD-3290 represents a highly specialized small molecule inhibitor specifically engineered to target the catalytic activity of Prostate-Specific Antigen (PSA/KLK3) with exceptional inhibitory potency. It effectively facilitates the measurable blockade of PSA-mediated proteolytic cleavage across various preclinical experimental models to evaluate the disruption of the tumor microenvironment during strictly monitored laboratory observation periods and enzyme kinetic assays to ensure high experimental sensitivity.

GSK962 is a GSK963 inactive enantiomer. It can be used to confirm the on-target effects.

Fusaric acid is an orally active multi-target inhibitor capable of inhibiting fibrosis-related signaling pathways such as NF-κB, TGF-β1/SMADs, and PI3K/AKT/mTOR. It also inhibits dopamine β-hydroxylase and reduces endogenous levels of norepinephrine and epinephrine. Fusaric acid activates apoptosis-related proteases such as Caspase-3/7, Caspase-8, and Caspase-9, thereby inducing oxidative stress and apoptosis. It chelates divalent metal cations, damages mitochondrial membrane structure, and exerts effects in improving myocardial fibrosis and alleviating cardiac hypertrophy. Additionally, it is applicable in research on esophageal cancer, liver cancer, and other conditions.

Indole-2-carboxylic acid is an indole carboxylic acid compound with multi-target biological activity, exhibiting neuroprotective, antiviral, and antioxidant properties. Indole-2-carboxylic acid is a competitive antagonist at the glycine site of the NMDA receptor (Ki = 15 μM). Indole-2-carboxylic acid specifically inhibits the potentiating effect of glycine on NMDA-gated currents, blocking the neurotoxicity caused by excessive NMDA receptor activation, and can be used in research on the treatment of neurodegenerative diseases and cerebral ischemic injury. Indole-2-carboxylic acid is also an HIV-1 integrase inhibitor; it interferes with the integration of viral DNA into the host genome and can be used in the development of anti-HIV drugs.

Bavisant dihydrochloride hydrate (JNJ31001074AAC) is a highly selective, orally active antagonist of the human H3 receptor with a novel mechanism of action related to wakefulness and cognition, and it has potential as a treatment for ADHD. In a clinical trial, the mean change from baseline in the total ADHD-RS-IV score at day 42 was -8.8 in the placebo group versus -9.3, -11.2, and -12.2 in the bavisant 1 mg/day, 3 mg/day, and 10 mg/day groups, respectively; however, the change in the 10 mg/day group was not statistically superior to placebo (p=0.161). Statistical comparisons of the 1 mg/day and 3 mg/day groups with placebo based on a step-down closed testing procedure were not performed. Bavisant has completed a phase II ADHD trial, but no results have been reported [1]. Clinical trial: A Study to Characterize the Pharmacokinetics and Effect of Food on JNJ-31001074 in Healthy Volunteers. Phase 2. IC50 Value: Target: H3 receptor in vitro.

DOTAP chloride (1, 2-dioleoyl-3-trimethylammonium-propane chloride) is an efficient cationic lipid, and its target is mainly the negatively charged components on the cell membrane. DOTAP chloride binds to negatively charged nucleic acids (such as DNA and RNA) by electrostatic interaction to form complexes, thereby achieving the delivery of nucleic acids.

Mavoglurant (AFQ056) is a potent, selective, non-competitive, and orally active metabotropic glutamate receptor 5 (mGluR5) antagonist with an IC50 of 30 nM, demonstrating greater than 300-fold selectivity over 238 tested targets, and it is widely applied in research on Fragile X syndrome and L-dopa-induced dyskinesias in Parkinson’s disease, while Mavoglurant incorporated alkyne functional group, which enables copper-catalyzed azide–alkyne cycloaddition click chemistry, facilitating target engagement and molecular tracking studies.

SAR-405 is a potent and selective PIK3C3/Vps34 inhibitor (IC50:1.2 nM; Kd:1.5 nM) that prevents autophagy and synergizes with MTOR inhibition in tumor cells. SAR405 treatment also inhibits autophagy induced either by starvation or by MTOR (mechanistic target of rapamycin) inhibition. Combining SAR405 with everolimus results in a significant synergy on the reduction of cell proliferation using renal tumor cells.

Acid-PEG4-C2-Boc, a linker compound based on polyethylene glycol (PEG) and alkyl/ether, is utilized in the synthesis of PROteolysis TArgeting Chimeras (PROTACs) for inhibiting the mechanistic Target of Rapamycin (mTOR)[1].

AGN 195183 is a potent and selective agonist of RARα(Kd=3 nM) with improved binding selectivity relative to AGN 193836; no activity on RARβ/γ. IC50 value: 3 nM (Kd); 200 nM (EC80, RAR Trans.) Target: RARα agonist Compound 4(AGN-195183) inhibited the growt

AMG 837 sodium salt is a potent GPR40 agonist(EC50=13 nM) with a superior pharmacokinetic profile and robust glucose-dependent stimulation of insulin secretion in rodents. IC50 value: 13 nM (EC50) [1] Target: GPR40 agonist AMG 837 displayed the expected t

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

BHPI is a potent inhibitor of nuclear estrogen receptor ERα–regulated gene expression that induces sustained ERα-dependent activation of the endoplasmic reticulum stress sensor and unfolded protein response, leading to persistent inhibition of protein synthesis, and in ERα-positive cancer cells it hyperactivates plasma membrane PLCγ to generate IP3, deplete ER calcium stores via IP3R channels, and convert the normally protective UPR into a toxic response, making BHPI a valuable probe for estrogen signaling and ER stress–based cancer research.

Biperiden Hydrochloride (KL 373 Hydrochloride) is an anticholinergic antiparkinsonian agent that selectively blocks central M1 cholinoreceptors while exerting atropine-like effects on peripheral parasympathetic structures. Biperiden Hydrochloride is approved for the adjunctive treatment of postencephalitic, idiopathic, and arteriosclerotic Parkinson’s disease, demonstrates minimal impairment of novelty preference compared with other anticholinergics in comparative cognitive studies, and is associated with known adverse effects including drowsiness, vertigo, headache, and dizziness.

PRN694 shows extended target residence time on ITK and RLK, enabling durable attenuation of effector cells in vitro and in vivo. PRN694 is an irreversible, highly selective, and effective covalent interleukin-2-inducible T-cell kinase (ITK) and resting ly