pi3k/mtor inhibitor 1

PI3K mTOR Inhibitor-1 is a potent, orally bioavailable dual inhibitor of PI3K mTOR (PI3Kα PI3Kβ PI3Kδ PI3Kγ mTOR with IC50s of 20 376 204 46 186 nM)

PI3K mTOR Inhibitor-12为口服有效且选择性的PI3K mTOR抑制剂，对PI3Kα和mTOR的IC50分别为0.06 nM及3.12 nM，表现出抗肿瘤活性且肝毒性较低。

PI3K mTOR Inhibitor-17 (compound 5nh) 是一种有效的 PI3K mTOR 抑制剂，对 PI3Kα 和 mTOR 的抑制浓度分别为 0.45 nM 和 2.9 nM。这种化合物在癌症研究中具有显著作用。

PI3K mTOR Inhibitor-13 是一种具有口服活性的磷酸肌醇 3-激酶 (PI3K) 和mTOR 激酶双重抑制剂。PI3K mTOR Inhibitor-13 在性疾病、实体瘤和特发性肺纤维化 (IPF) 中有潜在应用。

Torin 1 是一种 mTOR 抑制剂，可以抑制 mTORC1 和 mTORC2 (IC50=2 10 nM)，具有选择性和 ATP 竞争性。Torin 1 可以诱导细胞自噬，具有抗肿瘤、抗炎、抗衰老活性。

Dactolisib (BEZ235) 是一种可口服的 pan-class IPI3K 和 mTOR 抑制剂，抑制 mTORC1和 mTORC2，作用于 p110α γ δ β和 mTOR，IC50分别为 4 nM 5 nM 7 nM 75 nM 和 20.7 nM。

PI3K-IN-1 (Voxtalisib Analogue) 是 PI3K 抑制剂，PI3K-IN-1(25 μM) 能够阻断 PI3K Akt 信号通路。

AKT-IN-25 (Compound 14a) 是一种Akt抑制剂，通过抑制Akt的磷酸化，抑制PI3K Akt mTOR信号通路。AKT-IN-25 导致细胞周期在 G1 期停滞，抑制 PANC-1 的细胞迁移，并抑制癌细胞 PANC-1、PATU-T 和 SUIT-2 的增殖，其IC50分别为 3.05、1.32 和 3.85 μM。

Hederacolchiside A1 (Raddeanoside R13) 是从白头翁中分离的一种有抗利什曼原虫和抗肿瘤增殖活性的天然产物。

DCBCI0901 is an inhibitor of phosphatidylinositide 3-kinase (PI3K), raptor-mTOR (mTOR complex 1 or mTORC1) and rictor-mTOR (mTOR complex 2 or mTORC2) with potential antineoplastic activity.

DS-7423 是PI3K 和mTOR 的有效抑制剂，抑制PI3Kα 和 mTOR 的IC50分别为15.6 nM 和 34.9 nM。DS-7423表现出抗癌活性。

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.

Phosphoinositide 3-kinase (PI3K) and mammalian target of rapamycin (mTOR) act synergistically in promoting cancer. Wortmannin is a potent inhibitor of PI3K enzymes, while rapamycin blocks mTOR Complex 1 TORC1. Wortmannin-rapamycin conjugate consists of analogs of 17-hydroxy wortmannin and rapamycin conjugated via a prodrug linker. Hydrolysis of the prodrug linker in vivo releases the inhibitors. The wortmannin-rapamycin conjugate inhibits the growth of HT-29 colon tumors and A498 renal tumors in mice better than rapamycin alone. Also, the conjugate, when given in combination with the VEGF-blocker bevacizumab, produces substantial regression of larger A498 tumors. Finally, the wortmannin-rapamycin conjugate is tolerated better than an equivalent mixture of the inhibitors.

TBK1 IKKε-IN-4 is a 6-aminopyrazolopyrimidine derivative and a potent, selective TBK1 and IKKε inhibitor with IC50 values of 13 nM and 59 nM, respectively. TBK1 IKKε-IN-4 shows 100- to 1000-fold less activity against other protein kinases including PDK1, PI3K family members and mTOR[1]. TBK1 IKKε-IN-4 (Compound II; 96 hours; A549 andHCC44 cells) treatmentdisplays selective toxicity in TBK1-dependent cancer cell lines (IC50 of ~ 4.2 μM for H441 cells and IC50 of ~0.4 μM for A549 cells)[1].TBK1 IKKε-IN-4 (Compound II; 0-2 μM; 30 minutes; HCC44 cells) treatment inhibits the AKT activity[1].TBK1 IKKε-IN-4 (Compound II) inhibits LPS-induced expression of IFNβ (IC50 =62 nM), and the IFNβ target genes IP10 (IC50 =78 nM) and Mx1 (IC50=20 nM). TBK1 IKKε-IN-4 effectively blocksTLR3-dependent IRF3 nuclear translocation in cells with an IC50 under 100 nM, but does not impair TNFR1-dependent p65 NFκB nuclear translocation with doses as high as 20 μM[1]. [1]. Ou YH, et al. TBK1 directly engages Akt PKB survival signaling to support oncogenic transformation. Mol Cell. 2011 Feb 18;41(4):458-70.

PI-103 Hydrochloride 是一种有效的PI3K 和mTOR 双重抑制剂，抑制p110α，p110β，p110δ，p110γ，mTORC1和mTORC2，IC50分别为 8 nM，88 nM，48 nM，150 nM，20 nM 和 83 nM。PI-103 Hydrochloride 也可抑制DNA-PK，IC50为 2 nM。PI-103 Hydrochloride 诱导细胞自噬 (autophagy)。

PI3K mTOR Inhibitor-3 (compound 12) is an imidazoline compound with potent dual inhibitory effects on PI3K and mTOR. This compound exhibits notable anti-cancer activity [1].

PI3K mTOR Inhibitor-9 (Compound 1) 是一种 mTOR 和 PI3K 的有效抑制剂，能够作用于 mTOR (IC50: 38 nM)、PI3Kα (IC50: 6.6 nM)、PI3Kγ (IC50: 6.6 nM) 和 PI3Kδ (IC50: 0.8 nM)。

HDAC-IN-43 是一种强效的 HDAC 1 3 6 抑制剂，对 HDAC 1、HDAC 3 和 HDAC 6 的 IC50 值分别为 82 nM、45 nM 和 24 nM。HDAC-IN-43 是一种弱的 PI3K mTOR 抑制剂，对 PI3K 和 mTOR 的 IC50 值分别为 3.6 μM 和 3.7 μM。HDAC-IN-43 具有广谱的抗增殖效果。

ATM Inhibitor -4 是选择性的、强效的 ATM 抑制剂 (IC50: 0.32 nM)，较强的抑制PI3K 激酶家族的活性，并表现出良好的代谢稳定性。ATM Inhibitor-4 在 1 μM 时能完全抑制mTOR。

WYE-687 是 ATP 竞争性的 mTOR 抑制剂，其 IC50=7 nM。它能够抑制PI3Kα和PI3Kγ，IC50分别为 81 nM 和 3.11 μM。它能够抑制mTORC1和mTORC2活化。

Voxtalisib (XL765) 是一种PI3K 抑制剂，抑制p110α，p110β，p110γ和p110δ。它抑制mTORC1和mTORC2，IC50s 分别为 160 和 910 nM。它也抑制 DNA-PK (其 IC50=150 nM) 和 mTOR (其 IC50=157 nM)。

HSP90 mTOR-IN-1 是一种有效的Hsp90和mTOR 抑制剂，IC50分别为 69 nM 和 29 nM。HSP90 mTOR-IN-1 通过过度激活PI3K AKT mTOR 通路抑制 SW780 细胞增殖。HSP90 mTOR-IN-1 通过对HSP90和mTOR 的选择性抑制来诱导细胞凋亡 (apoptosis) 和细胞自噬 (autophagy)。HSP90 mTOR-IN-1 在异种移植小鼠体内也表现出良好的抗肿瘤活性。HSP90 mTOR-IN-1 可用于膀胱癌的研究。

PI3K mTOR Inhibitor-14（化合物 Y-2）是一种针对PI3K和mTOR的双重抑制剂，其IC50值分别为171.4 nM 和10.1 nM ，具备抗肿瘤活性。

ARI-1是一种针对受体酪氨酸激酶样孤儿受体ROR1的抑制剂，对于ROR1异常表达所致的非小细胞肺癌(NSCLC)及EGFR-TKI诱导的耐药性治疗具有显著效果。该化合物能够特异性结合至ROR1的胞外卷曲结构域，并以ROR1依赖性方式抑制PI3K AKT mTOR信号通路，进而有效地阻断NSCLC细胞的增殖和迁移。此外，ARI-1还展现了显著的体内抗肿瘤活性。