ps6

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.

APS6-45 inhibits RAS MAPK signaling and exhibits anti-tumor activity.

RPS6-IN-1 (Compound 22o) inhibits cell migration and induces apoptosis (increasing the expression of Bax, p53, cleaved-caspase 3, and cleaved-PARP). It reduces mitochondrial membrane potential and activates autophagy (Autophagy) through the PI3K-Akt-mTOR signaling pathway, damaging mitochondria and lysosomes within the cell and causing endoplasmic reticulum stress. RPS6-IN-1 also inhibits the phosphorylation of RPS6. Notably, RPS6-IN-1 is a low systemic toxicity anticancer agent.

Vistusertib (AZD2014) is an orally bioavailable inhibitor of the mammalian target of rapamycin (mTOR) with potential antineoplastic activity.

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.

BTX-6654 is a cereblon-based bifunctional SOS1 PROTAC degrader. This compound exhibits antiproliferative activity against cells with various KRAS mutations by reducing the expression of downstream signaling markers pERK and pS6.

DQ661 is a potent inhibitor of PPT1 and a dimeric quinacrine autophagy (autophagy) inhibitor. It effectively suppresses the activity of mTORC1 and reduces protein expression levels of pS6K T389 and pS6 S240-244. Additionally, DQ661 exhibits anticancer properties.

PIM-IN-1 is a pan-PIM kinase inhibitor with an EC50 of 61 nM in KG-1 and an EC50 of 71 nM in pS6.

PF-05139962 is a novel potent mTOR inhibitor with excellent mTOR biochemical inhibition, cellular potency, kinase selectivity and in vitro ADME properties. PF-05139962 has pS473 and pS6 cellular IC50 = 48 and 6 nM respectively. PF-05139962 has great selectivity against other receptors and kinases. No genotoxicity was observed on this compound and no more than 25% inhibiton was observed for major CYP enzymes (3A4, 1A2, 2C9, 2D6) at 3 uM. This compound has LE = 0.35 and LipE up to 6.8 which is in a very desirable range for a kinase inhibitor.

mTOR inhibitor-11 (Compound 9) is a brain-penetrant compound that inhibits mTOR with an IC50 of 21 nM for pS6 and exhibits inhibitory activity against pCHK1 and PDE4D with IC50 values of 17.2 μM and 17.0 μM, respectively. This compound is utilized in CNS disease research [1].

BC1618 (2-Propanol, 1-[bis(phenylmethyl)amino]-3-[4-(trifluoromethyl)phenoxy]-) is an orally active Fbxo48 inhibitor that stimulates Ampk-dependent signaling. It promotes mitochondrial fission, promotes autophagy and improves hepatic insulin sensitivity.