DHW-221

DHW-221 is a potent orally active dual PI3K/mTOR inhibitor, exhibiting low nanomolar potency against all four Class I PI3K isoforms and mTOR (PI3Kα, IC50 = 0.50 nM; PI3Kβ, IC50 = 1.9 nM; PI3Kγ, IC50 = 1.8 nM; PI3Kδ, IC50 = 0.74 nM; mTOR, IC50 = 3.9 nM) . DHW-221 exerts antitumor effects by blocking the PI3K/Akt/mTOR pathway and inducing mitochondrial apoptosis and paraptosis (via Endoplasmic Reticulum (ER) stress and MAPK signaling) and arrests cell cycle, thereby inhibiting cell migration, invasion and angiogenesis. DHW-221 inhibits tumor growth in both the A549/Taxol (HY-B0015) and the HCC827 xenograft mouse models. DHW-221 can be used for non-small cell lung cancer (NSCLC), colon and breast cancer research[1][2][3].

Product Specifications

CAS Number

[2378831-21-9]

UNSPSC

12352005

Target

Akt; Apoptosis; CDK; HIF/HIF Prolyl-Hydroxylase; Mitochondrial Metabolism; MMP; mTOR; p38 MAPK; Paraptosis; P-glycoprotein; PI3K; VEGFR

Related Pathways

Apoptosis; Cell Cycle/DNA Damage; MAPK/ERK Pathway; Membrane Transporter/Ion Channel; Metabolic Enzyme/Protease; PI3K/Akt/mTOR; Protein Tyrosine Kinase/RTK

Applications

Cancer-Kinase/protease

Field of Research

Cancer

Smiles

O=S(C1=CC=C(F)C=C1F)(NC2=CC(C3=CC=C4C(N(C5=CC=C(OCCO)C=C5)C=N4)=C3)=CN=C2OC)=O

Molecular Formula

C27H22F2N4O5S

Molecular Weight

552.55

References & Citations

[1]Ding HW, et al. Design, synthesis, and biological evaluation of some novel 4-aminoquinazolines as Pan-PI3K inhibitors. Bioorg Med Chem. 2019 Jul 1;27 (13) :2729-2740.|[2]Liu M, et al. DHW-221, a Dual PI3K/mTOR Inhibitor, Overcomes Multidrug Resistance by Targeting P-Glycoprotein (P-gp/ABCB1) and Akt-Mediated FOXO3a Nuclear Translocation in Non-small Cell Lung Cancer. Front Oncol. 2022 May 13;12:873649.|[3]Qin X, et al. Dual blocking of PI3K and mTOR signaling by DHW-221, a novel benzimidazole derivative, exerts antitumor activity in human non-small cell lung cancer. Clin Transl Med. 2021 Sep;11 (9) :e514.