internalization

CYM5442 是高选择性和口服活性的鞘氨醇 1-磷酸受体激动剂，EC50为 1.35 nM。它激活依赖 S1P1的 p42 p44-MAPK 磷酸化，具有视网膜神经保护作用，可轻松穿过中枢神经系统。

Rasarfin 是Ras 和ARF6双抑制剂。

SEW 2871 是一种可口服的高选择性 S1P1激动剂，EC50为 13.8 nM。它减少血液中的淋巴细胞数量，可用于糖尿病、阿尔茨海默氏病、肝纤维化和炎症相关研究。它激活 ERK、Akt 和 Rac 信号通路，并诱导 S1P1 内在化和再循环。

NUCC-390 是新型的选择性小分子 CXCR4 receptor 受体激动剂。NUCC-390 可以诱导 CXCR4 受体的内化，作用方式与 AMD3100相反。NUCC-390 在动物模型中，有助于神经退行性变后神经功能恢复。

Kukoamine B mesylate 是从地骨皮中提取得到的新型阳离子生物碱，具有抗氧化活性，抑制 Kupffer 和 RAW 264。7 细胞中的 LPS 内化，可用于研究急性炎症和糖尿病。

MPP+ iodide 是一种神经毒素 MPTP 的有毒代谢物，也是一种 5-羟色胺转运体 (SERT) 的高亲和力底物。MPP+ iodide 对多巴胺能神经元有毒，可以在动物模型中导致帕金森症。

ELA-14(human) acetate 是 ELA 的一个片段，它与 APJ 结合，激活 Gαi1 和 β-arrestin-2 信号通路，并类似于其亲本内源性肽诱导受体内化。

ACT-389949 是一种高效的甲酰肽受体 2 脂蛋白 A4 受体(FPR2) (ALX)选择性激动剂，对 FPR2 ALX 进行内化入单核细胞的EC50值为 3 nM。它对炎性疾病具有潜在的研究价值。

Tephrosin induces degradation of of EGFR and ErbB2 by inducing internalization of the receptors, has potent antitumor activities.

R 59-022 (DKGI-I) 是一种二酰基甘油激酶 （DGK） 抑制剂，也 是一种 5-HT Receptor 拮抗剂，可阻断宿主细胞中的丝状病毒内化。R 59-022 可激活蛋白激酶 C (PKC)，抑制肠平滑肌的收缩力，增强由1-油酰基-2-乙酰甘油诱导的 O2-产生。

BQ0413 对 PSMA 展现出优良亲和力，其 KD 为 89 pM。该化合物表现出显著的摄取和内化能力，在 PC3-pip 细胞中的内化率达到 44%。标记 99mTc 的 BQ0413 可用于肿瘤显像剂。

Selective medium-chain free fatty acid receptor GPR84 agonist (EC50 = 139 nM). Exhibits no response at GPR40, GPR41, GPR119 or GPR120 at 100 μM. Activates calcium mobilization, inhibits cAMP accumulation, and induces ERK1/2 phosphorylation, receptor desensitization and internalization in vitro. Liu et al (2016) Design and synthesis of 2-alkylpyrimidine-4,6-diol and 6-alkylpyridine-2,4-diol as potent GPR84 agonists. ACS Med.Chem.Lett. 7 579 PMID:27326330 |Zhang et al (2016) Discovery and characterization of a novel small-molecule agonist for medium-chain free fatty acid receptor G protein-coupled receptor 84. J.Pharmacol.Exp.Ther. 357 337 PMID:26962172

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.

R-8507 is a small molecule antagonist of the TNF-α type 1 receptor (TNF-αRI). It inhibits the expression of intercellular adhesion molecule-1 (ICAM-1) induced by TNF-α and IL-1β with EC50 values of 2.45 and 3.79 μM, respectively, in an ELISA using A549 lung epithelial cells.{|Gururaja2007|} It also disrupts the interaction of the TNF-αRI with receptor interacting protein 1 (RIP1) and TNF-αR-associated death domain protein (TRADD), preventing internalization of the receptor complex.

S1p receptor agonist 1 (S1p-receptor-agonist-1) 是有口服活性的S1P 受体激动剂，具有诱导 S1P1 内化的活性，EC50为9.83 nM。它有潜力用于关节炎和实验性自身免疫性脑炎)的相关研究。

NUCC-390 dihydrochloride 是新型的选择性小分子CXCR4receptor 受体激动剂。NUCC-390 dihydrochloride 可以诱导CXCR4受体的内化，作用方式与 AMD3100 相反。NUCC-390 dihydrochloride 在动物模型中，有助于神经退行性变后神经功能恢复。

HF51116 是 XCR4 的有效拮抗剂。HF51116 能够显著拮抗 SDF-1α 诱导的细胞迁移、钙动员和 CXCR4 内化，并利用 CXCR4 抑制 HIV-1 感染。HF51116 对HIV-1感染、造血干细胞动员和癌症转移表现出研究潜力。

Epofolate is folate receptor-targeting antimitotic agent with potential antineoplastic activity. Folate receptor-targeted epothilone BMS753493 contains an epothilone moiety linked to a single folate molecule. Mediated through the folate moiety, this agent delivers the antimitotic epothilone component into cells expressing folic acid receptors, frequently upregulated in many types of tumor cells. After ligand-receptor internalization, the epothilone moiety induces microtubule polymerization and stabilizes microtubules against depolymerization, resulting in the inhibition of mitosis and cellular proliferation. Check for active clinical trials or closed clinical trials using this agent. (NCI Thesaurus).

PD-1 PD-L1-IN-29(S4-1)，有效PD-1 PD-L1抑制剂，IC50值为6.1 nM。能够结合PD-L1，破坏PD-1 PD-L1相互作用，诱导PD-L1二聚化与内化，有助于改善其对内质网的定位并促进PD-L1进入内质网，展现出抗癌活性。

Bufrolin，作为Cromoglycate（组胺释放抑制剂）的类似物，是一种高效的GPR35激动剂，能够促进β-arrestin-2与人GPR35a或大鼠GPR35之间的相互作用。此外，Bufrolin亦可作为抗过敏性肥大细胞稳定剂，有效抑制内化肽诱导的抗炎反应，并且在内化肽连接药剂的药物递送研究中，被作为抗炎剂使用。

Anticanceragent 81（Compound 37b3）是用于诱导肿瘤细胞发生周期阻滞和凋亡（apoptosis）的化合物。当Anticanceragent 81作为有效载荷与Trastuzumab结合时，可生成抗体药物偶联物（ADC）T-PBA，此ADC保留了Trastuzumab的靶向特性和内化功能。

MC-GGFG-AM-(10Me-11F-Camptothecin) 是ZW251合成的Linker-Payload偶联物。ZW251是靶向人GPC3的抗体-活性分子偶联物(ADC)，包括人源化IgG1抗体、喜树碱(camptothecin)类的扑异构酶1抑制剂ZD06519及连接子（马来酰亚胺锚定和甘酰甘酰苯丙酰甘氨酸(GGFG)-氨基甲基(AM)可切割连接体）。该药物对人和食蟹猴GPC3具高亲和力，在表达GPC3的HCC细胞系中快速内化并可对GPC3阴性癌细胞进行旁观者介导杀伤。

Elabela(19-32) TFA 是ELABELA（ELA）与apelin受体(APJ)结合的活性片段，能激活Gαi1和β-arrestin-2信号通路，EC50值分别为8.6 nM和166 nM。该化合物可诱导受体内在化，降低动脉压，并对心脏具有正性肌力作用。

CCZ01048 TFA 是一种 α-MSH 类似物，与黑素皮质素1受体(MC1R)具有很高的结合亲和力，Ki 值为 0.31 nM。CCZ01048 TFA 具有快速内化 B16F10 黑色素瘤细胞和高体内稳定性。CCZ01048 TFA 是恶性黑色素瘤 PET 显像的一个有前途的制剂。