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Lu, Hongbo

Publications and source records attributed to Lu, Hongbo.

6 records
All sourcesNASA NTRSDOE OSTI
DOE OSTI2023

Discovery and characterization of a selective IKZF2 glue degrader for cancer immunotherapy

Malignant tumors can evade destruction by the immune system by attracting immune-suppressive regulatory T cells (Treg) cells. The IKZF2 (Helios) transcription factor plays a crucial role in maintaining function and stability of Treg cells, and IKZF2 deficiency reduces tumor growth in mice. Here we report the discovery of NVP-DKY709, a selective molecular glue degrader of IKZF2 that spares IKZF1/3. We describe the recruitment-guided medicinal chemistry campaign leading to NVP-DKY709 that redirected the degradation selectivity of cereblon (CRBN) binders from IKZF1 toward IKZF2. Selectivity of NVP-DKY709 for IKZF2 was rationalized by analyzing the DDB1:CRBN:NVP-DKY709:IKZF2(ZF2 or ZF2-3) ternary complex X-ray structures. Exposure to NVP-DKY709 reduced the suppressive activity of human Treg cells and rescued cytokine production in exhausted T-effector cells. In vivo, treatment with NVP-DKY709 delayed tumor growth in mice with a humanized immune system and enhanced immunization responses in cynomolgus monkeys. NVP-DKY709 is being investigated in the clinic as an immune-enhancing agent for cancer immunotherapy.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2015

Interfacial nucleation behavior of inkjet-printed 6,13 bis(tri-isopropylsilylethynyl) pentacene on dielectric surfaces

The performance of organic thin film transistors (OTFTs) is heavily dependent on the interface property between the organic semiconductor and the dielectric substrate. Device fabrication with bottom-gate architecture by depositing the semiconductors with a solution method is highly recommended for cost-effectiveness. Surface modification of the dielectric layer is employed as an effective approach to control film growth. Here, we perform surface modification via a self-assembled monolayer of silanes, a spin-coated polymer layer or UV-ozone cleaning, to prepare surfaces with different surface polarities and morphologies. The semiconductor is inkjet-printed on the surface-treated substrates as single-line films with overlapping drop assignment. Surface morphologies of the dielectric before film deposition and film morphologies of the inkjet-printed semiconductor are characterized with polarized microscopy and AFM. Electrical properties of the films are studied through organic thin-film transistors with bottom-gate/bottom-contact structure. With reduced surface polarity and nanoscale aggregation of silane molecules on the substrates, semiconductor nucleates from the interior interface between the ink solution and the substrate, which contributes to film growth with higher crystal coverage and better film quality at the interface. Surface treatment with hydrophobic silanes is a promising approach to fabrication of high performance OTFTs with nonpolar conjugated molecules via solution methods.

75 CONDENSED MATTER PHYSICS, SUPERCONDUCTIVITY AND↗