pi3k/mtor inhibitor-2

PI3K mTOR Inhibitor-2 is a potent pan inhibitor of PI3K and mTOR with IC50s of 3.4, 34, 16.1, and 4.7 nM for PI3Kα, PI3Kβ, PI3Kδ, PI3Kγ, and mTOR, respectively. PI3K mTOR Inhibitor-2 demonstrates antitumor activity.

Torin 1 is an effective inhibitor of mTORC1 2 with (IC50: 2 nM 10 nM); has 1000-fold selectivity for mTOR than PI3K.

PKI-402 is a potent PI3K and mTOR inhibitor. PKI-402 inhibits PI3Kα, mTOR, PI3Kβ, PI3Kδ and PI3Kγ with IC50s of 2, 3, 7, 14 and 16 nM, respectively.

PI3K Akt mTOR-IN-2 is a potent PI3K AKT mTOR inhibitor with anticancer effects and selectivity for MDA-MB-231 cells (IC50 2.29 μM). It induces cell cycle arrest and apoptosis in cancer cells.

Torin 2(IC50=0.25 nM), a specific and effective mTOR inhibitor, is the 800-fold greater specific activity for mTOR than PI3K and improves pharmacokinetic properties. The EC50 of Torin 2 for ATM ATR DNA-PK inhibition is 28 nM 35 nM 118 nM, respectively.

Pictilisib dimethanesulfonate (GDC-0941 2 MeSO3H salt) is a potent inhibitor of PI3Kα δ with IC50 of 3 nM, with modest selectivity against p110β (11-fold) and p110γ (25-fold).

NSC781406 is a highly effective inhibitor of PI3K and mTOR (IC50: 2 nM for PI3Kα).

Samotolisib (LY3023414) is an oral ATP competitive inhibitor of the class I PI3K isoforms, DNA-PK, and mTOR. Samotolisib (LY3023414) has been used in trials studying the treatment of Neoplasm, Solid Tumor, COLON CANCER, BREAST CANCER, and Advanced Cancer, among others.

PQR530 is a highly potent dual pan-PI3K mTORC1 2 inhibitor. PQR530 inhibited protein kinase B (PKB, pSer473) and ribosomal protein S6 (pS6, pSer235 236) phosphorylation with IC50 values of 0.07 μM. It also showing antitumor activity.

Apitolisib (RG 7422), an effective, class I PI3K inhibitor for PI3Kα(IC50=5 nM), PI3Kβ(IC50=27 nM), PI3Kδ(IC50=7 nM), PI3Kγ (IC50=14 nM), is used in trials study of solid cancers, breast cancer, prostate cancer, renal cell carcinoma, and endometrial carcinoma, among others.

AKT-IN-25 (Compound 14a) is an inhibitor of Akt that prevents the phosphorylation of Akt, thereby hindering the PI3K Akt mTOR signaling pathway. It arrests the cell cycle at the G1 phase, inhibits the migration of PANC-1 cells, and suppresses the proliferation of cancer cells PANC-1, PATU-T, and SUIT-2, with IC50 values of 3.05, 1.32, and 3.85 μM, respectively.

Topo I II-IN-2 (Compound 3g) is an inhibitor of both Topo I and Topo II. It exhibits inhibitory activity against NCI-H446 and NCI-H1048 cells with IC50 values of 1.30 μM and 1.42 μM, respectively. Topo I II-IN-2 induces mitochondrial apoptosis, disrupts mitochondrial function, and stimulates activity generation. Additionally, it inhibits the PI3K Akt mTOR pathway, effectively preventing the proliferation, invasion, and migration of small cell lung cancer (SCLC) cells in vitro.

Bimiralisib (PI3K-IN-2) is an orally bioavailable pan inhibitor of PI3K and inhibitor of the mTOR, with potential antineoplastic activity. PI3K-IN-2 inhibits the PI3K kinase isoforms alpha, beta, gamma and delta and, to a lesser extent, mTOR kinase, which may result in tumor cell apoptosis and growth inhibition in cells overexpressing PI3K mTOR. Activation of the PI3K mTOR pathway promotes cell growth, survival, and resistance to both chemotherapy and radiotherapy.

Jolkinolide B is a bioactive diterpene isolated from the roots of Euphorbia fischeriana Steud. Jolkinolide B induces apoptosis in cancer cells. Jolkinolide B can be used for studies on preventing and treating osteolysis.

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.

Compound 401 (2-morpholino-4H-pyrimido[2,1-a]isoquinolin-4-one) is a synthetic DNA-PK inhibitor (IC50 = 0.28 μM) that also targets mTOR but not PI3K.

DS-7423 is a dual PI3K and mTOR inhibitor, with IC50 values of 15.6 nM and 34.9 nM for PI3Kα and mTOR, respectively, and exhibits anti-tumor activity[1][2]. It increases TP53 expression, the level of p-TP53 on Ser-46, and induces apoptosis-related TP53 target genes (TP53AIP1 and PUMA) in OCCC cells[1]. DS-7423 also inhibits other isoforms of class I PI3K with IC50 values of 1,143 nM for PI3Kβ, 249 nM for PI3Kγ, and 262 nM for PI3Kδ[2]. [1]. Katsutoshi Oda, et al. Characterization of TP53 and PI3K signaling pathways as molecular targets in gynecologic malignancies. J Obstet Gynaecol Res. 2016 Jul;42(7):757-62. [2]. Tomoko Kashiyama, et al. Antitumor activity and induction of TP53-dependent apoptosis toward ovarian clear cell adenocarcinoma by the dual PI3K mTOR inhibitor DS-7423. PLoS One. 2014 Feb 4;9(2):e87220.

PKI-179 is a potent, orally active compound that functions as a dual PI3K mTOR inhibitor. It demonstrates IC50 values of 8 nM for PI3K-α, 24 nM for PI3K-β, 74 nM for PI3K-γ, 77 nM for PI3K-δ, and 0.42 nM for mTOR. Additionally, it is effective against E545K and H1047R mutations, with IC50s of 14 nM and 11 nM, respectively. In vivo studies have shown that PKI-179 possesses anti-tumor capabilities[1][2].

TBK1 IKKε-IN-4, a 6-aminopyrazolopyrimidine derivative, serves as a potent, selective inhibitor for TBK1 and IKKε, demonstrating IC50 values of 13 nM and 59 nM, respectively. This compound exhibits significantly reduced activity, by 100- to 1000-fold, against other protein kinases, such as PDK1, PI3K family members, and mTOR[1].

PI-103 is a potent, cell-permeable, ATP-competitive inhibitor of PI3K family members (IC50s: 2 3 3 15 30 23 nM for p110α β δ γ, mTOR, and DNA-PK).

PI-103 Hydrochloride is a potent dual inhibitor of PI3K and mTOR, demonstrating inhibitory IC50 values of 8 nM for p110α, 88 nM for p110β, 48 nM for p110δ, 150 nM for p110γ, 20 nM for mTORC1, and 83 nM for mTORC2, respectively. Additionally, it inhibits DNA-PK with an IC50 of 2 nM and induces autophagy [1] [2] [3] [4].

Voxtalisib (XL765) (SAR245409, XL765) is a dual inhibitor of mTOR PI3K, mostly for p110γ with IC50 of 9 nM; also inhibits DNA-PK and mTOR. Phase 1 2.

PI3K mTOR Inhibitor-14 (compound Y-2) is a dual inhibitor of PI3K and mTOR, with IC50 values of 171.4 nM and 10.1 nM, respectively, and exhibits antitumor activities [1].

LY303511, a structural analog of LY294002, selectively inhibits mTOR-dependent phosphorylation of S6K, unlike its counterpart, which acts as a phosphatidylinositol 3-kinase (PI3K) inhibitor. It effectively reduces cell proliferation in human lung epithelial adenocarcinoma cells by hindering G2/M phase progression and suppressing casein kinase 2 activity. Additionally, LY303511 enhances tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) sensitivity in HeLa cells resistant to TRAIL-induced apoptosis and blocks voltage-gated potassium (Kv) channels.