Synthesis of SHAL and SHAL Precursor Standard, CRADA No. TC02174.0 [electronic resource]

 0 Người đánh giá. Xếp hạng trung bình 0

Tác giả:

Ngôn ngữ: eng

Ký hiệu phân loại: 570 Life sciences Biology

Thông tin xuất bản: Livermore, Calif : Oak Ridge, Tenn. : Lawrence Livermore National Laboratory ; Distributed by the Office of Scientific and Technical Information, U.S. Dept. of Energy, 2014

Mô tả vật lý: Size: 15 p. : , digital, PDF file.

Bộ sưu tập: Metadata

ID: 262143

The purpose of this CRADA was to establish a collaborative effort between SHAL Technologies and Lawrence Livermore National Laboratory that would advance the development and testing of a family of small molecule oncology drugs and companion diagnostics called selective high affinity ligands (SHALs) for the treatment of advanced non-Hodgkin?s lymphoma. These compounds were first synthesized by the LLNL chemist participating in this CRADA when the compounds were first developed (2004-2008) by the founders of SHAL Technologies (while they were employed at LLNL). This CRADA initially had five deliverables. Deliverables 1-3 involved LLNL?s synthesis of 10-50 mg of the SHALs SH7133 and SH7139 using the same bench-scale conditions used previously, their purification, and obtaining data needed to demonstrate the mass and purity of the compounds. Deliverable 4, which was to be completed by SHAL Technologies, was the comparison of the bench-scale synthetic products to the same compounds manufactured on the multigram to kilogram scale by the contract research organization (CRO) AmbioPharm Inc. The fifth deliverable was this final report. An amendment was made to add the additional tasks and deliverables needed to synthesize the third SHAL standard SH7129 (the diagnostic) and compare it to product manufactured by AmbioPharm. During the testing of the three standards synthesized by LLNL, the SHAL compounds were found to lack biological activity. When we discovered that a commercial chemical supplier provided both LLNL and our CRO AmbioPharm with a SHAL precursor that had the wrong structure, two amendments to the CRADA were made to add additional tasks and deliverables to enable us to repeat all the syntheses and conduct more extensive testing of the bench scale and manufactured products. Once the final correct products were synthesized and confirmed to have the right structures, a third amendment was added to the CRADA to enable the synthesis of two fragments of the SHALs to determine if these compounds are produced when the SHALs are metabolized. This last synthesis was included to provide the information needed to establish a second, new CRADA between SHAL Technologies and LLNL that would focus on the identifying how the SHALs are metabolized and how their metabolic products may be responsible for the selective killing of tumor cells over-expressing the protein targeted by the SHALs, HLA-DR10.
Tạo bộ sưu tập với mã QR

THƯ VIỆN - TRƯỜNG ĐẠI HỌC CÔNG NGHỆ TP.HCM

ĐT: (028) 71010608 | Email: tt.thuvien@hutech.edu.vn

Copyright @2024 THƯ VIỆN HUTECH