on-target

Acalabrutinib (ACP-196) 是一种不可逆的、高效的、具有口服活性、选择性的第二代BTK 抑制剂。它与 BTK 的 ATP 结合口袋中的 Cys481 共价结合。它在慢性淋巴细胞性白血病 (CLL) 小鼠模型中显示出强大的靶向作用和功效。

Lenvatinib (E7080) 是一种多靶点受体酪氨酸激酶抑制剂，抑制 VEGFR1-3、FGFR1-4、KIT、PDGFR 和 RET 等，具有口服活性。Lenvatinib 对 VEGFR2 和 VEGFR3 的抑制活性最强 (IC50=4 5.2 nM)。Lenvatinib 具有强效抗肿瘤活性。

Triciferol 作为具有结合了 VDR 激动剂和 HDAC 拮抗剂活性的多重配体发挥作用。Triciferol 直接与 VDR 结合 (IC50=87 nM)，在一些 1,25D 靶基因上作为具有 1,25D 样效力的激动剂发挥作用。Triciferol 诱导显著的微管蛋白高乙酰化，并增强组蛋白乙酰化。Triciferol 在体外癌细胞模型中也表现出有效的抗增殖和细胞毒性活性。

SAR-405 是一种选择性 PIK3C3 Vps34 抑制剂，IC50为1.2 nM，Kd 为1.5 nM，可防止自噬并与肿瘤细胞中的 MTOR 抑制协同作用。它抑制饥饿或 mTOR 抑制诱导的自噬，具有抗癌活性。

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].

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 是 GSK963 的非活性对映异构体，可用于确认靶点作用。

Bavisant dihydrochloride hydrate (JNJ31001074AAC) is a highly selective, orally active antagonist of the human H3 receptor with a novel mechanism of action, involving wakefulness and cognition, with potential as a treatment for ADHD. in vivo: Mean change

Acid-PEG4-C2-Boc is a linker compound based on polyethylene glycol (PEG) and alkyl ether. It is utilized in the synthesis of PROteolysis TArgeting Chimeras (PROTACs) for the purpose of 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–ERα-regulated gene expression. Elicits sustained ERα-dependent activation of the endoplasmic reticulum (EnR) stress sensor, the unfolded protein response (UPR), and persistent inhibition of protein synthesis.

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) 是基于 LCL161 衍生物的细胞凋亡蛋白配体，可募集 IAP 泛素连接酶以降解靶蛋白，可用于和雄激素受体配体欧联开发蛋白降解剂，可用于研究前列腺癌。

VH032-cyclopropane-F 是基于 VH032 的 VHL 配体。它能够利用 linker 与靶蛋白配体连接，得到 PROTAC 分子，如 PROTAC 1。PROTAC 1 是 SMARCA2 和 SMARCA4 的部分降解剂。

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 是高选择性STAT3抑制剂。该化合物能特异性阻断STAT3-Tyr705的磷酸化及其靶基因的表达，对胰腺癌细胞表现出明显的细胞毒作用并可诱导细胞凋亡(apoptosis)。在胰腺癌模型的小鼠实验中，WB436B有效抑制了肿瘤的生长与转移，并显著延长了荷瘤小鼠的寿命。

AJI-214 是一种针对 Aurora Kinase A 和 JAK2 的双靶点抑制剂。通过直接阻断 Aurora Kinase A，AJI-214 抑制 T 细胞的有丝分裂进程和细胞极性。此外，它阻止 JAK2 的激活，从而抑制 STAT3 的磷酸化，减缓 TH1 和 TH17 细胞的分化。AJI-214 在调节免疫反应和预防移植物抗宿主病 (GVHD) 的研究中具有应用潜力。

TLX agonist 2 (compound 31) 作为一种高效的TLX激动剂，其激动特性由测定数据证实 (EC50=0.1 μM; Kd=0.16 μM)。该化合物通过与TLX结合，增强其转录活性，从而提升TLX靶基因的表达效率。此外，TLX agonist 2 主要应用于神经退行性疾病的相关研究领域。

DSPE-PEG(2000)-azide是一个基于1,2-distearoyl-sn-glycero-3-PE(1,2-DSPE)的PEG化化合物。该化合物用于将血管细胞黏附分子-1(VCAM-1)抗体与囊泡结合，这些囊泡内含有fingolimod，专门用于将fingolimod运送到模拟缺血后的神经炎症小鼠模型中的炎症血管。此外，DSPE-PEG(2000)-azide也被应用于连接纤维蛋白模拟肽(FMP)至合成血小板，以治疗小鼠模型中由肝损伤引发的无法控制的出血。

(R)-SR-C-107 是一种口服有效的抑制剂，专为ENL（含 YEAST 结构域蛋白）抑制而设计，用于抗急性髓系白血病（AML）。其针对ENL的IC50和KD分别为40 nM和144 nM。在异种移植AML的小鼠模型中表现出体内效能，以每公斤体重200毫克（PO; QD）剂量下，肿瘤消退率达到45%。

CCW16-C9-BocNH，由RING finger protein 4 (RNF4) 招募配体、含有亲水和疏水基团的连接体以及与目标配体羧酸反应的悬挂胺组成，在靶向蛋白降解和PROTAC研究中的蛋白降解剂开发和合成中起重要作用。