nuclear export

Leptomycin B (LMB) 是一种抗真菌抗生素，可阻断真核细胞周期，抑制蛋白出核转运。Leptomycin 通过半胱氨酸残基处的共价修饰使 CRM1 exportin 1失活。

KPT-251 是一种选择性核输出抑制剂。

GNF4877 是一种 DYRK1A (IC50:6 nM) 和 GSK3β (IC50:16 nM) 抑制剂。 它导致激活 T 细胞核因子核输出的阻断和 β 细胞增殖细胞增加。

(E)-KPT330 是一种 CRM1 选择性核输出抑制剂。它抑制细胞核中的蛋白质运输并诱导间皮瘤细胞中的细胞周期停滞和凋亡。

Eltanexor (ONO-7706) 是一种具有口服活性的 exportin-1 (XPO1) 抑制剂。它具有有效的抗白血病活性。 Eltanexor 通过直接靶向 XPO1 抑制 XPO1 依赖性核输出 (EC50=60.9 nM)。 Eltanexor 在一组白血病细胞系中引起半胱天冬酶依赖性细胞凋亡。

Leptomycin A, a metabolite derived from Streptomyces, acts as an inhibitor of CRM1 (exportin 1) and effectively suppresses HIV-1 replication. Compared to Leptomycin B, it exhibits lesser potency. Leptomycin A hampers the interaction between CRM1 and nuclear export signals, effectively hindering the nuclear export of a wide array of proteins.

CBS9106 (SL-801) 是一种可逆的口服 CRM1 抑制剂，具有降解 CRM1 和抗肿瘤活性。CBS9106 可抑制 CRM1 依赖性核输出，降低 CRM1 蛋白水平。CBS9106 抑制肿瘤生长并延长携带肿瘤异种移植物的小鼠的存活时间。

Leptomycin B (GMP)是 Leptomycin B 的 GMP 级别试剂。Leptomycin B 是一种抗真菌抗生素，可阻断真核细胞周期，抑制蛋白出核转运。Leptomycin B (GMP) 通过半胱氨酸残基处的共价修饰使 CRM1 exportin 1失活。

PKF050-638 inhibits the CRM1-mediated Rev nuclear export by disrupting CRM1-NES interaction. PKF050-638 is an effective and selective inhibitor of HIV-1 Rev (IC50=0.04 μM).

Psammaplysene A is a FOXO1a nuclear export inhibitor.

Psammaplysene B is a FOXO1a nuclear export inhibitor.

Bile acids are essential for solubilization and transport of dietary lipids, are the major products of cholesterol catabolism, and are physiological ligands for farnesoid X receptor (FXR), a nuclear receptor that regulates genes involved in lipid metabolism.1They are also inherently cytotoxic, as physiological imbalance contributes to increased oxidative stress.2,3Bile acid-controlled signaling pathways are promising novel targets to treat such metabolic diseases as obesity, type II diabetes, hyperlipidemia, and atherosclerosis.Guggulsterone, derived from resin of the guggul tree, is a competitive antagonist of FXR bothin vitroandin vivo.4Thecisstereoisomer of guggulsterone, (E)-guggulsterone, decreases chenodeoxycholic acid (CDCA)-induced FXR activation with an IC50value of 15 μM.5,6By inhibiting CDCA-induced transactivation of FXR, guggulsterone lowers low-density lipoprotein cholesterol and triglyceride levels in rodents fed a high cholesterol diet.4 1.Makishima, M., Okamoto, A.Y., Repa, J.J., et al.Identification of a nuclear receptor for bile acidsScience2841362-1365(1999) 2.Barbier, O., Torra, I.P., Sirvent, A., et al.FXR induces the UGT2B4 enzyme in hepatocytes: A potential mechanism of negative feedback control of FXR activityGastroenterology1241926-1940(2003) 3.Tan, K.P., Yang, M., and Ito, S.Activation of nuclear factor (erythroid-2 like) factor 2 by toxic bile acids provokes adaptive defense responses to enhance cell survival at the emergence of oxidative stressMol. Pharmacol.72(5)1380-1390(2007) 4.Urizar, N.L., Liverman, A.B., Dodds, D.T., et al.A natural product that lowers cholesterol as an anatagonist ligand for FXRScience296(5573)1703-1706(2002) 5.Cui, J., Huang, L., Zhao, A., et al.Guggulsterone is a farnesoid X receptor antagonist in coactivator association assays but acts to enhance transcription of bile salt export pumpThe Journal of Biological Chemisty278(12)10214-10220(2003) 6.Wu, J., Xia, C., Meier, J., et al.The hypolipidemic natural product guggulsterone acts as an antagonist of the bile acid receptorMolecular Endocrinology16(7)1590-1597(2002)

KPT276 (KPT 276) 是一种口服生物可利用的核输出选择性抑制剂(SINE)，不可逆地与 CRM1 结合并阻断 CRM1 的功能。

TTC-352 is an orally bioavailable selective human estrogen receptor alpha (ERalpha; ESR1; ERa) partial agonist (ShERPA), with potential antineoplastic activity. Upon administration, TTC-352 mimics the naturally-occurring 17beta-estradiol (E2) and targets and binds to ERa located in the nucleus. This causes translocation of ERa to extranuclear sites. Nuclear export of ERa prevents normal ER-mediated signaling and inhibits proliferation of ER-positive tumor cells.

CRM1-IN-1 (Compound KL1) 为非共价CRM1抑制剂，能诱导核CRM1降解（IC50: 0.27 μM），抑制CRM1介导的核输出与细胞增殖，同时触发结直肠癌细胞凋亡 (apoptosis)。

CRM1-IN-2（Compound KL2）为非共价CRM1抑制剂，能够定位CRM1于核外围，耗尽核内CRM1，从而抑制CRM1介导的核输出。该化合物能抑制结直肠癌细胞的生长并诱导细胞凋亡（apoptosis）。

Anti-Influenza agent 5 (Compound IIB-2)为查耳酮类衍生物，具有抑制流感病毒核输出的活性。该化合物能有效抑制对Oseltamivir具有耐药性的病毒株，主要通过阻断流感病毒核蛋白输出作用来抑制病毒复制。