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Antibiotic Arenavirus Bacterial CMV Enterovirus Filovirus Fungal HBV HCV HCV Protease HIV HIV Integrase HIV Protease HSV Influenza Virus Orthopoxvirus Parasite TMV Reverse Transcriptase RSV SARS-CoV Virus Protease RABV HPV DENV RABV
Apoptosis

Apoptosis Bcl-2 Family Caspase c-Myc DAPK Ferroptosis FKBP IAP Family MDM-2/p53 PKD Necroptosis Pyroptosis RIP kinase Thymidylate Synthase TNF Receptor TRADD Cuproptosis DAPK
Autophagy

Autophagy FKBP LRRK2 Mitophagy OGA ULK Beclin1 Atg4
Cell Cycle/DNA Damage

Antifolate APC ATM/ATR Aurora Kinase BMI-1 Casein Kinase CDK Checkpoint Kinase (Chk) CRISPR/Cas9 Deubiquitinase DNA Alkylator/Crosslinker DNA/RNA Synthesis DNA-PK Early 2 Factor (E2F) Eukaryotic Initiation Factor (eIF) GAK G-quadruplex Haspin Kinase HDAC HSP IRE1 Kinesin LIM Kinase (LIMK) Microtubule/Tubulin Mps1 DNA Stain Nucleoside Antimetabolite/Analog p97 PAK PARP PERK PFKFB3 Polo-like Kinase (PLK) PPAR RAD51 Cyclin G-associated Kinase (GAK) ROCK ATF6 Haspin Kinase Sirtuin SRPK PDI Telomerase TOPK Topoisomerase Wee1 YB-1 poly (ADP ribose) glycohydrolase (PARG) OGG1
Cytoskeletal Signaling

Arp2/3 Complex Dynamin Gap Junction Protein Integrin Kinesin Microtubule/Tubulin Mps1 Myosin PAK ROCK
Epigenetics

AMPK Aurora Kinase DNA Methyltransferase Epigenetic Reader Domain HDAC Histone Acetyltransferase Histone Demethylase Histone Methyltransferase MicroRNA PARP PKC Protein Arginine Deiminase Methionine Adenosyltransferase (MAT) Sirtuin JAK TET Protein
GPCR/G Protein

5-HT Receptor Adenosine Receptor Adenylate Cyclase (AC) Adrenergic Receptor Angiotensin Receptor Bombesin Receptor Bradykinin Receptor Cannabinoid Receptor CaSR CCR CGRP Receptor Cholecystokinin Receptor CRFR CXCR TSH Receptor Neuropeptide Y Receptor Dopamine Receptor EBI2/GPR183 Endothelin Receptor Formyl peptide receptor (FPR) GHSR Glucagon Receptor GNRH Receptor GPR109A GPR119 GPR139 GPR27 GPR55 GPR84 Guanylate Cyclase Histamine Receptor Imidazoline Receptor Leukotriene Receptor LPL Receptor mAChR MCHR1 (GPR24) Melanocortin Receptor Melatonin Receptor mGluR Motilin Receptor Neurokinin Receptor Neurotensin Receptor Opioid Receptor Orexin Receptor (OX Receptor) Oxytocin Receptor P2Y Receptor PKG Prostaglandin Receptor Protease-Activated Receptor (PAR) Apelin Receptor (APJ) Ras GPR88 Free Fatty Acid Receptor RGS GPR4 Secretin Receptor Mas-related G-protein-coupled Receptor (MRGPR) GPR35 GPR52 MCHR1 (GPR24) Leukotriene Receptor GLP Receptor Somatostatin Receptor Arrestin Platelet-activating Factor Receptor (PAFR) Mas-related G-protein-coupled Receptor (MRGPR) Kisspeptin Receptor G Protein-coupled Receptor Kinase (GRK) G protein-coupled Bile Acid Receptor 1 Succinate Receptor 1 TSH Receptor Protease Activated Receptor (PAR) Urotensin Receptor Vasopressin Receptor Motilin Receptor TF
Immunology/Inflammation

Arginase Aryl Hydrocarbon Receptor (AhR) CCR Complement System COX CXCR Cyclic GMP-AMP Synthase (cGAS) TIM-3 TIGIT CTLA-4 FKBP FLAP Galectin IFNAR Interleukin Related IRAK MIF MyD88 NO Synthase NOD-like Receptor (NLR) PD-1/PD-L1 PGE synthase CX3CR1 Pyroptosis Nuclear Factor of activated T Cells (NFAT) Reactive Oxygen Species AP-1 Salt-inducible Kinase (SIK) SOD SPHK STING Thrombopoietin Receptor Toll-like Receptor (TLR) AP-1 PSMA Glucocorticoid Receptor (GR) FAP Histamine Receptor Macrophage migration inhibitory factor (MIF) LAG-3 Mucin Tim3 Mesothelin Nectin-4 P-selectin TROP2 CD79B DPEP3 BCMA MUC16 BAFF CD markers FcRn CSF2 IgE Glycoprotein VI

Epigenetics

表观遗传学包括改变基因活性而不改变 DNA 序列的任何过程，并导致可以传递给子细胞的修饰。已经鉴定了许多类型的表观遗传过程 - 它们包括 DNA 甲基化，组蛋白结构的改变和小的非编码微小 RNA 的基因调节。

已经鉴定出许多不同的 DNA 和组蛋白修饰以确定表观遗传景观。 DNA 甲基化主要由 DNA 甲基转移酶 (DNMT) 介导，有两种已知类型的 DNMT，即 DNMT1，其保留细胞复制后预先存在的甲基化模式，和 DNMT3A/B，即所谓的“从头” DNMT，其中甲基化以前未甲基化的 DNA。组蛋白修饰主要包括乙酰化，甲基化，磷酸化和泛素化。组蛋白的乙酰化可以通过组蛋白乙酰转移酶 (HAT) 和组蛋白去乙酰转移酶 (HDAC) 介导，而组蛋白去甲基化通过两类组蛋白去甲基化酶进行：赖氨酸特异性脱甲基酶 (LSD) 家族蛋白 (LSD1和LSD2) 和含有组蛋白的 JmjC 结构域。脱甲基酶 (JHDM) 。此外，参与表观遗传修饰的酶也可以由 miRNA 控制。例如，miR-34a 可以直接抑制SIRT 1的活性以调节胆固醇体内平衡。

组蛋白的各种翻译后修饰使用了许多参与蛋白上几个共价附着物的添加或删除的酶特定组蛋白残基。这些酶功能的改变或失调是恶性生长的与恶性生长有关的因此，新疗法的发展方向是这些酶对治疗癌症是有益的。目前组蛋白去乙酰化酶抑制剂是临床上唯一被批准的改变组蛋白的表观遗传疗法。然而，正在不断努力开发特定的抑制剂靶向其他各种参与组蛋白改变的酶。下图总结了各种表观遗传药物靶点。

图1 ：各种表观遗传药物靶点

Biswas S, et al. Pharmacol Ther. 2017 May:173:118-134.

累积的证据表明，许多基因，疾病和环境物质是表观遗传学图片的一部分。在 FDA，科学家正在研究许多通过表观遗传机制起作用的药物。已经研究了抑制 DNA 甲基化或组蛋白脱乙酰化的药物用于肿瘤抑制基因的再激活和癌细胞生长的抑制。表观遗传抑制剂也可单独使用或与其他治疗剂组合使用。

参考文献：
[1]. Bob Weinhold. Epigenetics: the science of change. Environ Health Perspect. 2006 Mar; 114(3): A160–A167.
[2]. Xu W, et al. Epigenetics and Cellular Metabolism. Genet Epigenet. 2016 Sep 25;8:43-51.
[3]. Biswas S, et al. Epigenetics in cancer: Fundamentals and Beyond. Pharmacol Ther. 2017 May:173:118-134.
[4]. Perri F, et al. Epigenetics in cancer: Fundamentals and Beyond. Crit Rev Oncol Hematol. 2017 Mar;111:166-172.

Epigenetics 相关靶点

AMPK (84) Aurora Kinase (53) DNA Methyltransferase (24) Epigenetic Reader Domain (142) HDAC (135) Histone Acetyltransferase (42) Histone Demethylase (43) Histone Methyltransferase (107) MicroRNA (14) PARP (105) PKC (82) Protein Arginine Deiminase (8) Methionine Adenosyltransferase (MAT) (6) Sirtuin (72) JAK (128) TET Protein (5)