PI3K/Akt/mTOR Signaling

<p>HER2-IN-12 is an HER2 inhibitor with an IC50 value of 121 nM and can be used to study cancers such as breast cancer.</p>

<p>Neptinib (NEP010), a derivative of Afatinib, exhibits enhanced antitumor properties and improved pharmacokinetics when administered orally. It demonstrates a notable suppression of tumor expansion in mouse models of non-small cell lung cancer harboring various EGFR mutations. Furthermore, Neptinib effectively inhibits the EGFR kinase family, exhibiting IC 50 values of 0.24 nM for EGFR wt, 7.25 nM for EGFR L858R/T790M, 0.46 nM for EGFR L858R, and 1.79 nM for EGFR T790M.</p>

<p>PI4KIII beta inhibitor 5 (Compound 43) is an inhibitor of PI4KIIIβ with an IC50 of 19 nM. By inhibiting the PI3K/AKT pathway, it induces apoptosis in cancer cells, causes cell cycle arrest at the G2/M phase, and promotes autophagy. Additionally, PI4KIII beta inhibitor 5 demonstrates significant anti-tumor activity in the H446 small cell lung cancer xenograft model. This compound is applicable in cancer research studies.</p>

<p>JBJ-02-112-05 is a potent, mutant-selective, allosteric and orally active inhibitor of EGFR with an IC 50 of 15 nM for EGFR L858R/T790M [1].</p>

<p>Lys(CO-C3-p-I-Ph)-O-tBu, a pharmacokinetic modifier (PK modifier), enhances the pharmacokinetic properties of PSMA ligand molecules by increasing their residence time in plasma through improved binding to albumin and reducing absorption by the salivary glands, potentially extending the active compound's half-life. Moreover, Ac-PSMA-trillium is an effective PSMA-targeting compound for various biological applications when modified with different radioactive isotopes. When labeled with 111 In, it serves as a DOTA chelating agent and imaging agent. Alternatively, when labeled with 225 Ac, it acts as a Macropa chelator for targeted radionuclide therapy (TRT) in researching metastatic castration-resistant prostate cancer (mCRPC) [1] [2].</p>

<p>EG31 is an EGFR inhibitor that effectively suppresses the proliferation of triple-negative breast cancer (TNBC) cells by inhibiting the EGFR signaling pathway. It demonstrates a GI50 value of 498.90 nM for MDA-MB-231 cells and 740.73 nM for Hs578T cells, while also inducing apoptosis. Additionally, EG31 retains its antiproliferative activity against 5-fluorouracil (5-FU) resistant TNBC cells, with a GI50 of 519.5 nM. EG31 is applicable in research on TNBC resistance.</p>

<p>EGFR/HER2-IN-7: Potent, selective dual inhibitor for MCF-7 cancer; IC50: EGFR 0.18μM, HER2 0.146μM, DHFR 0.907μM.</p>

<p>SIK2/3-IN-1 (Compound 7S) is an orally active and selective inhibitor of SIK2/3. It significantly inhibits tumor growth without causing weight loss in the MV4-11 AML mouse CDX model. SIK2/3-IN-1 is applicable for research in MEF2C-dependent acute myeloid leukemia.</p>

<p>EGFR-IN-17: potent, selective EGFR inhibitor, IC50 of 0.2 nM, overcomes C797S drug resistance.</p>

<p>PIKfyve-IN-1: potent, cell-active inhibitor for PIKfyve research, IC50=6.9 nM.</p>

<p>EGFR-IN-38: low-toxic acrylamide-derived EGFR inhibitor, targets NSCLC, patented for research on EGFR mutation-related diseases.</p>

<p>LSD1/EGFR-IN-1 (compound L-1) is an effective inhibitor of LSD1, EGFRT790M/L858R, and EGFRL858R/T790M/C797S, with IC50 values of 6.24, 2.06, and 5.01 μM, respectively. This compound plays a significant role in cancer research.</p>

<p>JBJ-09-063: EGFR inhibitor, IC50s 0.147-0.396 nM for various mutants; hinders EGFR/Akt/ERK1/2 phosphorylation; targets TKI-sensitive/resistant lung cancer.</p>

<p>PI3K-IN-23 is a (E)-9-oxooctadec-10-en-12-ynoic acid analogue that promotes glucose uptake (EC50: 7.00 μM).</p>

<p>Sacibertinib inhibits Trk, targeting EGFR-TK (EC50 110 nM) &amp; HER2 (EC50 244 nM), with anticancer properties.</p>

<p>Vulolisib inhibits PI3K (α: IC50 0.2nM, β: 168nM, γ: 90nM, δ: 49nM), taken orally with anti-cancer properties.</p>

<p>HER2-IN-6, a potent HER2 inhibitor, may target wild/mutant EGFR and HER2-mediated tumors. (Patent WO2021164697A1, compound 11)</p>

<p>Aldometanib (LXY-05-029) is an oral aldolase inhibitor that maintains metabolic balance by blocking FBP and activating lysosomal AMPK.</p>

<p>AZD 3147 inhibits mTORC1 (40.7 nM), mTORC2 (5.75 nM), and PI3Kα/β/δ/γ (912/5495/9333/6310 nM IC50s).</p>

<p>BAY-8400 is an orally active, potent and selective DNA-dependent protein kinase ( DNA-PK ) inhibitor ( IC 50 =81 nM) which shows synergistic efficacy in</p>

<p>EGFR-IN-7 (TQB3804) is a selective and potent EGFR kinase inhibitor.</p>

<p>Sonolisib is an irreversible and pan-isoform inhibitor of PI3K (IC50=0.1 nM (p110α), 1.0 nM (p120γ), 2.9 nM (p110δ)).</p>

<p>Tyrosine-protein kinase ABL, IC50: 1500 nM</p>

<p>HMBD-001 is a humanized IgG1 monoclonal antibody inhibitor that targets HER3. By inhibiting the dimerization of HER3, HMBD-001 suppresses the growth and proliferation of tumor cells. It holds potential for research in cancer treatments, specifically for pancreatic cancer and non-small cell lung cancer.</p>

<p>mTORC1-IN-1 (T1), a rapamycin homologue (rapalog) and selective inhibitor of mTORC1, controls cell growth and metabolism, with implications in various diseases</p>

<p>Nimotuzumab (powder) is a humanized IgG1 monoclonal antibody that specifically targets the epidermal growth factor receptor (EGFR), possessing a dissociation constant (KD) of 0.21 nM. It blocks the binding to its ligand by targeting the extracellular domain of EGFR. Nimotuzumab exhibits strong antitumor activity by inducing both antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC), exerting cytolytic effects on target tumors.</p>

<p>AZD8154 is a newly developed inhaled compound that selectively inhibits dual PI3Kγδ, aimed at treating airway inflammatory diseases.</p>

<p>AS-604850: PI3Kγ inhibitor, ATP-competitive, IC50=2.5μM, 30x&gt; PI3Kδ/β, 18x&gt; PI3Kα.</p>

<p>PDK1-IN-RS2, a PIFtide mimic, selectively inhibits PDK1, blocking S6K1 activation (Kd: 9 μM).</p>

<p>Duligotuzumab (MEHD-7945A) is a bispecific humanised IgG-κ monoclonal antibody targeting HER3 and EGFR, solid tumours, head and neck cancer,colorectal cancer.</p>

<p>Bisindolylmaleimide I HCl is a specific ATP-competitive PKC inhibitor.</p>

<p>EGFR-IN-82 (Compound 8a) is a potent, orally active inhibitor of EGFR, exhibiting IC50 values of 0.09 nM for EGFR L858R/T790M/C797S and 0.06 nM for EGFR Del19/</p>

<p>Duvelisib R enantiomer (IPI-145 R enantiomer) is an enantiomer of Duvelisib with lower activity. Duvelisib is a PI3K inhibitor.</p>

<p>PI3Kδ-IN-13 (compound 89), with an IC50 value of 2.6 nM, is an inhibitor of PI3Kδ, applicable for researching diseases involving cell proliferation, including</p>

<p>MDVN1003 inhibits BTK &amp; PI3Kδ in B cells, blocking NHL growth; it kills lymphoma cells, not erythroblasts.</p>

<p>YK-029A, an orally active EGFR mutant inhibitor, targets both EGFR T790M and EGFRex20ins mutations.</p>

<p>EGFR-IN-123 (compound D06) is an effective EGFR inhibitor. It exhibits inhibitory activity against several cell lines including PC-9G, A549, A431, and HCT116, with IC50 values of 0.74, 1.36, 1.20, and 2.53 μM respectively.</p>

<p>EGFR-IN-122 (compound Yfq07) serves as a potent inhibitor of EGFR. It effectively inhibits the proliferation of PC-9GR and HCC827GR cells.</p>