apogossypol (CNDO103) / Fortress - LARVOL DELTA

Gossypol and Semi-synthetic Derivatives: Chemistry, Bioactivities and Mechanism of Actions. (PubMed, Chem Biodivers) - "Furthermore, gossypol serves as a core molecule for synthesizing various derivatives, such as gossypol Schiff bases, gossypolone and apogossypol, which are less toxic yet retain similar therapeutic benefits...Recent studies have shown promise in reducing gossypol's toxicity through the synthesis of derivatives, while advanced drug delivery methods, including nanocarriers, have been explored to enhance its therapeutic efficacy. Furthermore, gossypol has demonstrated significant synergistic potential when used in combination with conventional anticancer drugs, offering new avenues for cancer therapy."

Journal • Oncology

Practical Strategy to 1,1'-Dideoxygossypol Derivatives from Gossypol and Its Antitumor Activities. (PubMed, ACS Omega) - "The key step is the successful regioselective deacetylation of hexaacetyl apogossypol 9 and the following reductive removal of hydroxyl groups...The antitumor results illustrate that 1,1'-hydroxyl groups are not necessary for antitumor activities. In addition, 1,1'-dideoxygossypol has superior aqueous solubility (215 mg/L) compared to gossypol (64 mg/L)."

Journal • Oncology

Structure, properties of gossypol and its derivatives-from physiological activities to drug discovery and drug design. (PubMed, Nat Prod Rep) - "The design and synthesis of pharmacologically active derivatives based on the structure of gossypol, such as gossypol Schiff bases, apogossypol, gossypolone, are thoroughly discussed. This review aims to serve as a reference for gossypol-based drug discovery and drug design."

Journal • Review • Oncology

Anti-tumor compounds identification from gossypol Groebke imidazopyridine product. (PubMed, Bioorg Chem) - "Compound 4 was found to display good anti-proliferative activities for 7 human cancer cell lines (0.33-1.7 µM) among them, which were better than separate gossypol and imidazopyridine moiety compounds. It was capable of suppressing antiapoptotic proteins Bcl-2 and Bcl-X demonstrated by mechanism studies, and possible binding model was also illustrated by molecular modelling."

Journal • Oncology • BCL2L1

Apogossypol-mediated reorganisation of the endoplasmic reticulum antagonises mitochondrial fission and apoptosis. (PubMed, Cell Death Dis) - "Strikingly, both ER membrane reorganisation and its resulting inhibition of apoptosis could be reversed by inhibitors of dihydroorotate dehydrogenase (DHODH), namely teriflunomide and its active metabolite, leflunomide. However, neither genetic inhibition of DHODH using RNA interference nor metabolic supplementation with orotate or uridine to circumvent the consequences of a loss of DHODH activity rescued the effects of DHODH inhibitors, suggesting that the effects of these inhibitors in preventing ER membrane reorganisation is most likely independent of their ability to antagonise DHODH activity. Our results strengthen the hypothesis that ER is fundamental for key mitochondrial functions, such as fusion-fission dynamics and apoptosis."

Journal

Broad spectrum BH3 mimetic BI-97D6 induces apoptosis of acute myeloid leukemia cells even when co-cultured with supporting stromal cells (AACR 2012) - Presentation Time: Monday, Apr 02, 2012, 1:00 PM - 5:00 PM; BI-97D6 does not induce CHOP expression or JNK activation; There was no difference in BI-97D6 mediated killing of OCI-AML3 cells whether the cells were treated in co-culture with BM MSC or alone

Oncology