PI3K/Akt/mTOR Signaling

<p>EGFR-IN-17: potent, selective EGFR inhibitor, IC50 of 0.2 nM, overcomes C797S drug resistance.</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>GSK-3β inhibitor20 (compound 3A) is an effective inhibitor of GSK-3β, exhibiting an IC50 value of 74.4 nM.</p>

<p>EGFR-IN-48: potent EGFR inhibitor, oral, IC50: 0.193-66.7 nM, blocks EGFR mutants &amp; BaF3/PC-9 cell proliferation.</p>

<p>EGFR-IN-18 strongly inhibits L858R/T790M/C797S mutant EGFR (4.9 nM) and also targets wild-type EGFR (47 nM).</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>PIKfyve-IN-1: potent, cell-active inhibitor for PIKfyve research, IC50=6.9 nM.</p>

<p>EGFR-IN-159 (compound 12) is a dihydropyrimidine and a potent EGFR inhibitor with an IC50 of 29.00 nM. It exhibits dose-dependent inhibition of EGFR and HER2. The compound shows cytotoxicity against MCF-7 breast cancer cells and Vero cells with IC50 values of 16.07 μg/mL and 35.98 μg/mL, respectively. EGFR-IN-159 does not cross the blood-brain barrier (BBB) and demonstrates significant anticancer activity.</p>

<p>GSK3-IN-9 (0713) is a selective inhibitor of glycogen synthase kinase 3 (GSK3). It holds potential for research into fragile X syndrome, attention deficit hyperactivity disorder (ADHD), childhood epilepsy, intellectual disabilities, diabetes, acute myeloid leukemia (AML), autism, and mental disorders.</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>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>PI3Kδ-IN-23 (compound A11) is a potent inhibitor of PI3Kδ, with an IC50 of 0.27 nM. It binds to PI3Kδ through covalent interaction with Lys779 and plays a significant role in cancer research.</p>

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

<p>SST0116CL1 is an HSP90 inhibitor (IC50: 0.21 μM) that targets the ATP-binding pocket of Hsp90, disrupting its chaperone function and leading to the degradation of client proteins (EGFR, CDK4, and AKT). It induces the degradation of Her2 in BT-474 cells (IC50: 0.2 μM) and exhibits antiproliferative activity, inhibiting tumor growth.</p>

<p>PI3kδ inhibitor 1 is a selective inhibitor of PI3Kδ (IC50 of 3.8 nM).</p>

<p>ETP-47037: strong PI3Kα inhibitor (IC50: 0.99 nM), also targets PI3Kβ, δ, γ; may protect telomeres.</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>Aldometanib (LXY-05-029) is an oral aldolase inhibitor that maintains metabolic balance by blocking FBP and activating lysosomal AMPK.</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>AS-604850: PI3Kγ inhibitor, ATP-competitive, IC50=2.5μM, 30x&gt; PI3Kδ/β, 18x&gt; PI3Kα.</p>

<p>Tyrosine-protein kinase ABL, IC50: 1500 nM</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>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>AZD8154 is a newly developed inhaled compound that selectively inhibits dual PI3Kγδ, aimed at treating airway inflammatory diseases.</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>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>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>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>Duvelisib R enantiomer (IPI-145 R enantiomer) is an enantiomer of Duvelisib with lower activity. Duvelisib is a PI3K inhibitor.</p>

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

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