HDAC
Histone deacetylases (HDACs) are enzymes that catalyze the removal of acetyl functional groups from the lysine residues of both histone and nonhistone proteins. In humans, there are 18 HDAC enzymes that use either zinc- or NAD+-dependent mechanisms to deacetylate acetyl lysine substrates. The Class I proteins (HDAC1, HDAC2, HDAC3, and HDAC8) have sequence similarity to the yeast Rpd3 protein. The Class II proteins (HDAC4, HDAC5, HDAC6, HDAC7, HDAC9, and HDAC10) have sequence similarity to the yeast Hda1 protein. The Class III proteins (SIRT1, SIRT2, SIRT3, SIRT4, SIRT5, SIRT6, and SIRT7) have sequence similarity to the yeast Sir2 protein. The Class IV protein (HDAC11) shares sequence similarity to both Class I and II proteins.
HDAC1 is phosphorylated by cAMP-dependent kinase PKA and protein kinase CK2. HDAC3 can also be phosphorylated by GSK-3b, and inhibition of GSK-3b protects against HDAC3-induced neurotoxicity. The subcellular localization is regulated by the binding of the 14-3-3 proteins to a phosphorylated HDAC4. . Aurora A (AurA) phosphorylates HDAC6 to activate tubulin deacetylase activity. Cell cycle –dependent kinase cyclin B/Cdk1 phosphorylates SIRT1, JNK1 phosphorylates SIRT1 at S27, S47, and T530, and this phosphorylation of SIRT1 increased its nuclear localization and enzymatic activity. HDACs modulate the function of many proteins through nonhistone deacetylation, HDACs potentially play a role in nearly every aspect of health and disease. Numerous reports document the involvement of HDACs in cancer, neurodegenerative diseases, metabolic disorders, inflammatory diseases, immunological disorders, cardiac diseases, and pulmonary diseases.
References
1.Seto E, Yoshida M. Cold Spring Harb Perspect Biol 2014;6:a018713
HDAC1 is phosphorylated by cAMP-dependent kinase PKA and protein kinase CK2. HDAC3 can also be phosphorylated by GSK-3b, and inhibition of GSK-3b protects against HDAC3-induced neurotoxicity. The subcellular localization is regulated by the binding of the 14-3-3 proteins to a phosphorylated HDAC4. . Aurora A (AurA) phosphorylates HDAC6 to activate tubulin deacetylase activity. Cell cycle –dependent kinase cyclin B/Cdk1 phosphorylates SIRT1, JNK1 phosphorylates SIRT1 at S27, S47, and T530, and this phosphorylation of SIRT1 increased its nuclear localization and enzymatic activity. HDACs modulate the function of many proteins through nonhistone deacetylation, HDACs potentially play a role in nearly every aspect of health and disease. Numerous reports document the involvement of HDACs in cancer, neurodegenerative diseases, metabolic disorders, inflammatory diseases, immunological disorders, cardiac diseases, and pulmonary diseases.
References
1.Seto E, Yoshida M. Cold Spring Harb Perspect Biol 2014;6:a018713
Cell Cycle/DNA Damage
ABC(12)
AChR(104)
Antifolate(12)
ATM/ATR(26)
Aurora Kinase(51)
CLK(15)
c-Myc(22)
DHFR(16)
DNA Alkylator(34)
DNA gyrase(11)
DNA Repair Protein(21)
DNA/RNA Synthesis(187)
DNA-PK(15)
GPR(97)
HDAC(152)
Hec1/Nek2(9)
Integrin(77)
LIM Kinase (LIMK)(7)
Mps1/TTK(2)
Nucleoside Antimetabolite/Analog(48)
Other Targets(4)
PAK(13)
PARP(67)
PLK(26)
Potassium Channel(146)
RAD51(1)
Rho(16)
ROCK(42)
Telomerase(12)
Topoisomerase(88)
Wee1(7)
HDAC
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YPX-C-05
产品货号 : M37338
cas no: 2894823-79-9
YPX-C-05 是一种基于异羟肟酸的 HDAC 抑制剂。YPX-C-05 具有显着的血管舒张作用。YPX-C-05 对 HDAC 表现出抑制作用,并增加内皮细胞中的组蛋白 H4 乙酰化。YPX-C-05 可用于高血压研究。 -
HDAC-IN-57
产品货号 : M36851
cas no: 2716217-79-5
HDAC-IN-57 是一种具有口服活性的组蛋白脱乙酰酶 (HDAC) 泛抑制剂,对 HDAC1, HDAC2, HDAC6, HDAC8 的 IC50 值分别为 2.07 nM, 4.71 nM, 2.4 nM 和 107 nM。HDAC-IN-57 可抑制 LSD1,对 LSD1 的 IC50 值为 1.34 μΜ。HDAC-IN-57 诱导凋亡 (apoptosis),具有抗肿瘤活性。 -
MC2590
产品货号 : M36538
cas no: 2284460-01-9
MC2590 是一种有效的含吡啶的组蛋白脱乙酰酶 (HDAC) 抑制剂。MC2590 是 HDAC1-3、-6、-8 和 -10 的抑制剂 (I/IIb 类选择性抑制剂),IC50 为 0.015 μM-0.156 μM。MC2590 还抑制其他 HDAC 型, HDAC4、HDAC5、HDAC7 、HDAC9、HDAC11,IC50 为 1.35 μM-3.98 μM。MC2625 诱导 G2/M 细胞周期停滞并调节促凋亡和抗凋亡 microRNA 以诱导细胞凋亡。 -
TYA-018
产品货号 : M36531
cas no: 2653254-31-8
TYA-018 是一种口服有效且高度选择性的 HDAC6 抑制剂。TYA-018 可以保护小鼠的心脏功能。TYA-018 还通过增加与脂肪酸代谢、蛋白质代谢和氧化磷酸化相关的靶标的表达来增强小鼠的能量。 -
ITF3756
产品货号 : M36305
cas no: 2247608-27-9
ITF 3756 是一种有效的选择性 HDAC6 抑制剂。ITF 3756 在体外降低人单核细胞和 CD8 T 细胞上 PD-L1 的表达,并显示出抗肿瘤活性。