min-3

ASM-IN-3 (Compound 21b) 是一种选择性且能穿透血脑屏障的acid sphingomyelinase (ASM)抑制剂，其对纯化的人ASM的IC50为3.37 μM。ASM-IN-3 通过抑制海马区的ASM活性并促进神经发生，改善Reserpine诱导的抑郁大鼠的抑郁样行为。

UGM-IN-3 (compound 10a) 是一种 UDP-吡喃半乳糖变位酶 (UGM) 抑制剂，Kd 为 66 μM。UGM-IN-3 抑制结核分枝杆菌的生长，MIC 值为 6.2 μg mL。

Maximin 3是一种抗菌肽，来源于Bombina maxima的皮肤分泌物。它对肿瘤细胞表现出细胞毒性，并具有杀精作用。此外，Maximin 3还展示出显著的抗HIV活性。

Maximin 31 是抗菌肽，源自蟾蜍大脑。该化合物对金黄色葡萄球菌和大肠杆菌表现出抗菌活性，其最小抑菌浓度（MIC）值分别为 37.5 μg mL 和 75 μg mL。

Maximin 32 是源于蟾蜍大脑的抗菌肽，对金黄色葡萄球菌和大肠杆菌表现出活性，其 MIC 值分别为 9.4 和 18.8 μg mL。

Maximin 39为源自蟾蜍大脑的抗菌肽，具有针对金黄色葡萄球菌（Staphylococcus aureus）和大肠杆菌（Escherichia coli）的活性，其最小抑菌浓度（MIC）值分别为18.8 μg mL和37.5 μg mL。

Ovalbumin is the main protein found in egg white, making up 60-65% of the total protein. Ovalbumin is an important protein in several different areas of research, including general studies of protein structure and properties. Ovalbumin is used for studies

Antiflammin 3（MQMNKVLDS）属于抗炎肽类化合物。

AM679 is a potent and selective FLAP inhibitor with IC50s of 2.2 nM 0.6 nM 154 nM for FLAP binding hLA hWB respectively. IC50 value: 2.2 nM 0.6 nM 154 nM(FLAP binding hLA hWB) [1] AM679 showed an improved CYP inhibition profile (IC50 3A4 = 16.7 lM, 2C9 =

CYP3A4-IN-4（compound Δ,Λ-3）是一个结合了Ru(II)与Ir(III)的化合物，能作为人体主要的药物代谢酶CYP3A4的光活性抑制剂使用。这种化合物包含了[Ru(tpy)(Me2bpy)]的光笼结构群，在经过光照处理（λirr=530 nm，tirr=15 min）后，其对微粒体CYP3A4的抑制半数最大效应浓度(IC50)为2.2 μM。此外，CYP3A4-IN-4的光治疗指数（PI）达到5.4。

pan-TEAD-IN-1 (Compound 3) 是一种可口服的TEAD泛抑制剂，通过靶向TEAD的棕榈酰化位点，干扰其与共激活因子YAP TAZ的相互作用，从而抑制Hippo信号通路中癌基因（如Ctgf和Cyr61）的转录上调。pan-TEAD-IN-1 展现出优异的活性，对luciferase的IC50为0.36 nM，对H226细胞的IC50为1.52 nM，并拥有良好的药代动力学特性 (AUC0–∞= 228.7 μg mL·min，T1 2= 183.9 min)。在TEAD依赖型癌症的异种移植小鼠模型中，该化合物显著抑制肿瘤生长，具有研究TEAD依赖型癌症的潜力。

AZD1283是P2Y12受体拮抗剂，EC50为3.0 ug kg min，结合的IC50为11 nM。它剂量依赖性地诱导血流量增加和抑制 ADP 诱导的血小板聚集，抗血栓形成的 ED50 值分别为 3.0 和 10 μg kg min。

PI3Kα-IN-4 is a potent, selective and orally active inhibitor of PI3Kα, with an IC50 of 1.8 nM. PI3Kα-IN-4 has antitumor activity[1]. PI3Kα-IN-4 (compound 10) inhibits PI3Kα, β, δ, and γ, with IC50s of 1.8, 271.0, 13.9, and 13.8 nM, respectively in kinase assays[1].PI3Kα-IN-4 inhibits PI3Kα, β, δ, and γ, with IC50s of 12.1,1393, 183, and >10000 nM, respectively in cell based assays[1]. PI3Kα-IN-4 (compound 10) (30 mg kg; p.o. once daily for 21 d) achieves the best efficacy, which could inhibit tumor growth by 73.0% in mice[1].PI3Kα-IN-4 (15-40 mg kg; p.o. once daily for 30 d) dose dependently suppresses tumor growth by 62.5% (15 mg kg), 86.0% (30 mg kg) and 90.7% (40 mg kg), respectively in mice[1].PI3Kα-IN-4 (15-40 mg kg; p.o. once daily; 1-4 h) inhibits the phosphorylation of Akt in a dose- and time-dependent manner in vivo[1].PI3Kα-IN-4 shows high Cmax (mouse 22167, rat 2327 nM) and good bioavailability (mouse 59.4%, rat 46.9%) following oral administration (mouse 10, rat 3 mg kg)[1].PI3Kα-IN-4 shows t1 2 (mouse 0.99, rat 1.22 h) and low plasma clearance (mouse 4.16, rat 5.28 mL min kg) following intravenous injection (mouse 1, rat 1 mg kg)[1]. [1]. Dong J, et, al. Discovery of 3-Quinazolin-4(3 H)-on-3-yl-2, N-dimethylpropanamides as Orally Active and Selective PI3Kα Inhibitors. ACS Med Chem Lett. 2020 Jun 10; 11(7): 1463-1469.

CC-90005 is a potent, selective and orally active inhibitor of protein kinase C-θ (PKC-θ), with an IC50 of 8 nM. CC-90005 shows selectivity for PKC-θ over PKC-δ (IC50=4440 nM). CC-90005 can inhibit T cell activation by IL-2 expression[1]. CC-90005 shows the exquisite selectivity of CC-90005, with IC50s for all other family members of >3 μM[1].CC-90005 is a moderate inhibitor of both CYP2C9 (IC50=8 μM) and CYP2C19 (IC50=5.9 μM) in human liver microsomes[1].CC-90005 inhibits IL-2 expression in LRS_WBC human PBMCs, with an IC50 of 0.15 μM[1].CC-90005 (1-10 μM; 24 h) inhibits T cell proliferation in PBMCs by 51% at 1 μM and 88% at 3 μM[1]. CC-90005 (3-30 mg kg; p.o. twice daily for 4 days) significantly reduces the popliteal lymph node (PLN) size in a model of chronic T cell activation[1].CC-90005 (100 mg kg; a single p.o.) significantly inhibits plasma and spleen IL-2 release by 51 and 54%, respectively[1].CC-90005 exhibits reasonable oral bioavailability (66 and 46%) and Cmax (1.18 and 1.2 μM) following oral administration (10 and 3 mg kg) in rat and dog, respectively[1].CC-90005 exhibits the mean residence time (0.52 and 2.0 h), CL (69.1 and 20.5 mL min kg) and Vss (2.11 and 2.44 L kg) following intravenous administration (2 and 1 mg kg) in rat and dog, respectively[1]. [1]. Papa P, et, al. Discovery of the Selective Protein Kinase C-θ Kinase Inhibitor, CC-90005. J Med Chem. 2021 Aug 26;64(16):11886-11903.

PKI-179 is a potent and orally active dual PI3K mTOR inhibitor, with IC50s of 8 nM, 24 nM, 74 nM, 77 nM, and 0.42 nM for PI3K-α, PI3K-β, PI3K-γ, PI3K-δ and mTOR, respectively. PKI-179 also exhibits activity over E545K and H1047R, with IC50s of 14 nM and 11 nM, respectively. PKI-179 shows anti-tumor activity in vivo[1][2]. PKI-179 inhibits the cell proliferation, with IC50s of 22 nM and 29 nM for MDA361 and PC3 cells, respectively[1].PKI-179 shows inhibitory activity against a panel of 361 other kinases, hERG and cytochrome P450 (CYP) isoforms at concentrations up to >30 μM, but does have activity for CYP2C8 (IC50=3 μM)[1]. PKI-179 (5-50 mg kg; p.o. once daily for 40 days) inhibits the tumor growth and is well tolerated in nude mice bearing MDA-361 human breast cancer tumors[1].PKI-179 (50 mg kg; p.o.) results in good inhibition of PI3K signaling in nude mice bearing MDA361 tumor xenografts[1].PKI-179 exhibits good oral bioavailability (98% in nude mouse, 46% in rat, 38% in monkey, and 61% in dog) and a high half-life (>60 min) [1]. [1]. Venkatesan AM, et, al. PKI-179: an orally efficacious dual phosphatidylinositol-3-kinase (PI3K) mammalian target of rapamycin (mTOR) inhibitor. Bioorg Med Chem Lett. 2010 Oct 1;20(19):5869-73.[2]. Rehan M. A structural insight into the inhibitory mechanism of an orally active PI3K mTOR dual inhibitor, PKI-179 using computational approaches. J Mol Graph Model. 2015 Nov;62:226-234.

RWJ-56110 dihydrochloride is a potent, selective, peptide-mimetic inhibitor of PAR-1 activation and internalization (binding IC50=0.44 uM) and shows no effect on PAR-2, PAR-3, or PAR-4. RWJ-56110 dihydrochloride inhibits the aggregation of human platelets induced by both SFLLRN-NH2 (IC50=0.16 μM) and thrombin (IC50=0.34 μM), quite selective relative to U46619 . RWJ-56110 dihydrochloride blocks angiogenesis and blocks the formation of new vessels in vivo. RWJ-56110 dihydrochloride induces cell apoptosis[1][2]. Proteinase-activated receptors (PARs) are a family of G protein-coupled receptors activated by the proteolytic cleavage of their N-terminal extracellular domain, exposing a new amino terminal sequence that functions as a tethered ligand to activate the receptors.RWJ56110 inhibits the aggregation of human platelets induced by both SFLLRN-NH2 (IC50=0.16 μM) and thrombin (IC50=0.34 μM) while being quite selective relative to collagen and the thromboxane mimetic U46619 [1].RWJ-56110 dihydrochloride is fully inhibits thrombin-induced RASMC proliferation with an IC50 value of 3.5 μM. RWJ-56110 dihydrochloride shows blockade of thrombin's action with RASMC calcium mobilization (IC50=0.12 μM), as well as with HMVEC (IC50=0.13 μM) and HASMC calcium mobilization (IC50=0.17 μM)[1].RWJ56110 (0.1-10 μM; 24-96 hours) inhibits endothelial cell growth dose-dependently, with half-maximal inhibitory concentration of RWJ56110 is approximately 10 μM[2].RWJ56110 (0.1-10 μM; 6 hours) inhibits DNA synthesis of endothelial cells in a thymidine incorporation assays. Endothelial cells are in fast-growing state (50-60% confluence), RWJ56110 inhibits cell DNA synthesis in a dose-dependent manner, but when cells that are in the quiescent state (100% confluent), the inhibitory effect of PAR-1 antagonists is much less pronounced[2].RWJ56110 (0.1-10 μM; pretreatment for 15 min) inhibits thrombin-induced Erk1 2 activation in a concentration-dependent manner. However, when endothelial cells are stimulated by FBS (final concentration 4%), it reduces partially the activated levels of Erk1 2[2].RWJ56110 (30 μM; 24 hours) has an inhibitory effect on endothelial cell cycle progression. It reduces the percentage of cells in the S phase, while alterations in the percentages of G1 and G2 M cells are less pronounced[2]. Western Blot Analysis[2] Cell Line: Endothelial cells [1]. Andrade-Gordon, et al.Design, synthesis, and biological characterization of a peptide-mimetic antagonist for a tethered-ligand receptor. oc Natl Acad Sci U S A. 1999 Oct 26;96(22):12257-62. [2]. Panagiota Zania, et al. Blockade of angiogenesis by small molecule antagonists to protease-activated receptor-1: association with endothelial cell growth suppression and induction of apoptosis. J Pharmacol Exp Ther. 2006 Jul;318(1):246-54.

LEO 39652 is a dual-soft PDE4 inhibitor with IC50s of 1.2 nM, 1.2 nM, 3.0 nM and 3.8 nM for PDE4A, PDE4B, PDE4C and PDE4D, respectively. LEO 39652 also inhibits TNF-α with an IC50 value of 6.0 nM. LEO 39652 is used for topical research of Atopic dermatitis (AD) [1]. LEO 39652 shows unbound in vitro potency when measured as LPS induced TNF-α release in human peripheral blood mononuclear cells (PBMC), incubated in serum free medium. LEO 39652 shows a relatively high binding to human serum albumin[2]. LEO 39652 is inactivated both in blood and liver (dual-soft) while stabled in the skin[1].Pharmacokinetic AnalysisLEO 39652 exhibits total clearance (rats 930, minipigs 200 and monkey 300 mL min kg) and ratio to total AUC (rats 4, minipigs 6 and monkey 6 %) following intravenous administration (rats 0.075, minipigs 0.5 and monkeys 2.0 mg kg)[1]. [1]. Jens Larsen, et al. Discovery and Early Clinical Development of Isobutyl 1-[8-Methoxy-5-(1-oxo-3 H-isobenzofuran-5-yl)-[1,2,4]triazolo[1,5- a]pyridin-2-yl]cyclopropanecarboxylate (LEO 39652), a Novel Dual-Soft PDE4 Inhibitor for Topical Treatment of Atopic Dermatitis. J Med Chem. 2020 Dec 10;63(23):14502-14521.[2]. Stefan Eirefelt

Piperazine (2HCl) is gamma-aminobutyric acid (GABA) agonists and its major effects appear to be on the central nervous system. Piperazine was the anthelmintic with the greatest number of reports of toxicoses and suspected toxicoses in cats. Piperazine neurotoxicity in cats and dogs usually was manifested by muscle tremors, ataxia, and or behavioral disturbances within 24 hours after estimated daily dose(s) between 20 and 110 mg kg[1]. For di-substituted derivatives, ciprofloxacin was selected and hybrids were synthesized via substitution at piperazinyl-N4. The reaction of piperazinyl-NH of ciprofloxacin with selected drugs resulted in pronounced growth inhibition of standard as well as resistant bacterial strains[2]. The parent piperazine 6 was found to exhibit a reasonable activity toward the HeLa and MDA MB 231 tumor cell lines (IC50= 9.2 and 8.4 μΜ, respectively)[3]. Piperazine adipate (10 mM) causes mortality of A. galli and H. gallinae after a maximum of 30 min exposure, inhibits malate oxidation by 78%, and inhibits aldolase activity in both parasites. Piperazine adipate (10 mM) also inhibits cholinesterase activity by 96% in Ascaridia galli (A. galli) and 93% in Heterakis gallinae (H. gallinae). Piperazine adipate inhibits oxaloacetate reduction by 26% and 55% in A. galli and H. gallinae, resepctively[4].

PD-85639 is a voltage-gated sodium (Na+) channel blocker (75% in 10 min & >95% in 25 min blockage of Na+ current by 25 μM PD85,639; whole-cell patch clamp using primary rat brain neurons) that is shown to target rat brain Nav1.2 with simultaneous high- and low-affinity modes of binding (EC50 = 56 nM 40% & 20 μM 60% at pH 9.0, 5 nM 28% & 3 μM 72% at pH 7.4, against 2 nM [3H]-PD85,639 for binding rat brain synaptosomes; EC50 = 17 nM 39% & 10 μM 61% using at pH 9.0 using rat brain synaptosome membranes) and a fast kinetic (t1 2 = 1.2 at 4°C, <0.5 min at 25°C), competitive against the local anesthetic Na+ channel blockers tetracaine, bupivacaine, and mepivacaine, as well as Na+ channel activators veratridine and batrachotoxin (K1 = 0.26 μM against 5 nM [3H]-BTX for binding rat neocrotical membranes).

A2AR-antagonist-1 (compound 38) 为一种口服活性的腺苷 A2A 受体 (A2AR) 拮抗剂，IC50 值为 29 nM。此化合物展示出抗肿瘤作用，并在小鼠肝微粒体中表现出良好的代谢稳定性，半衰期为 86.1 分钟。同时，A2AR-antagonist-1 能够作为 T 细胞激活剂，通过抑制免疫抑制分子 LAG-3 和 TIM-3，以及增强 GZMB、IFNG 和 IL-2 等效应分子的表达。

CK2-IN-9是一种有效的CK2 kinase选择性抑制剂，IC50值为3 nM。它能降低Wnt报告因子的活性，达到IC50为75 nM。在大鼠体内显示出低暴露量（AUC=0.36 μM h）及高清除率（CL=65 mL min kg）。