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.

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].

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

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

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.

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 ERα inhibitor that blocks nuclear estrogen–ERα-regulated gene expression effectively. It triggers sustained ERα-dependent activation of the endoplasmic reticulum (EnR) stress sensor, notably the unfolded protein response (UPR), and consistently inhibits protein synthesis. With an IC50 value targeting ERα, BHPI's mechanism involves the rapid hyperactivation of PLCγ on the plasma membrane in ERα(+) cancer cells, which produces inositol 1,4,5-triphosphate (IP3). This, in turn, opens EnR IP3R calcium channels, leading to a rapid depletion of EnR Ca(2+) stores. SIGNIFICANTLY, BHPI alters estrogen-ERα's usual effect of causing mild and transient UPR activation by inducing a severe and prolonged UPR activation, transforming the UPR from a protective to a toxic response.

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

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

cIAP1 ligand 1 (E3 ligase Ligand 12) is an apoptotic protein ligand based on the LCL161 derivative that recruits IAP ubiquitin ligases to degrade target proteins, and can be used in conjunction with androgen receptor ligands for the development of protein degradation agents that can be used in the study of prostate cancer.

VH032-cyclopropane-F is a VHL ligand based on VH032. It is able to utilize linkers to ligands of target proteins to yield PROTAC molecules such as PROTAC 1. PROTAC 1 is a partial degrader of SMARCA2 and SMARCA4.

Imazamethabenz is a herbicide. Imazamethabenz-methyl is used on cereals and sunflowers, especially against wild oat. Activity and selectivity are due to differential de-esterification to the active parent acid in target and crop species.

WB436B, a highly selective STAT3 inhibitor, effectively targets and inhibits STAT3-Tyr705 phosphorylation along with the expression of STAT3 target genes. It exhibits cytotoxic effects on pancreatic cancer cells by inducing apoptosis. Furthermore, WB436B suppresses tumor growth and metastasis in pancreatic cancer mouse models, thereby prolonging the survival of tumor-bearing mice.

AJI-214 functions as a dual-target inhibitor that specifically blocks Aurora kinase A and JAK2. By directly inhibiting Aurora kinase A, AJI-214 prevents mitotic progression and cell polarity in T cells while concurrently suppressing JAK2 activation to reduce STAT3 phosphorylation. This inhibition decreases the differentiation of TH1 and TH17 cells. AJI-214 is utilized in research focused on the modulation of immune responses and the prevention of graft-versus-host disease (GVHD).

TLX agonist 2 (compound 31) is a TLX agonist with an EC50 of 0.1 μM and a Kd of 0.16 μM. This compound enhances transcriptional activity by binding to TLX, thereby boosting the expression of TLX target genes. TLX agonist 2 is utilized in research on neurodegenerative diseases.

DSPE-PEG(2000)-azide is a PEGylated derivative based on 1,2-distearoyl-sn-glycero-3-phosphoethanolamine (1,2-DSPE). This compound is utilized for attaching vascular cell adhesion molecule-1 (VCAM-1) antibodies to vesicles that encapsulate fingolimod, aiming to target the delivery of fingolimod to inflammatory vessels in mouse models simulating post-ischemic neuroinflammation. Additionally, DSPE-PEG(2000)-azide is employed to link fibrinogen mimetic peptides (FMP) to the surface of synthetic platelets used in treating uncontrollable bleeding caused by liver damage in mouse models.

(R)-SR-C-107 is an orally active inhibitor developed based on ENL (containing YEAST domain protein), designed to target acute myeloid leukemia (AML). The inhibitor has an IC50 of 40 nM and a KD of 144 nM for ENL. In a xenograft mouse model of AML, (R)-SR-C-107 demonstrated in vivo efficacy, achieving a tumor regression rate of 45% at a dosage of 200 mg kg (PO; QD).

CCW16-C9-BocNH is composed of an RING finger protein 4 (RNF4)-recruiting ligand, includes a linker with both hydrophobic and hydrophilic elements, and features a pendant amine that reacts with a carboxylic acid on the target ligand. It is crucial for synthesizing protein degraders used in targeted protein degradation and PROTAC research.