CB002 / Fox Chase Cancer Center, Pennsylvania State University - LARVOL DELTA

A subset of CB002 xanthine analogs bypass p53-signaling to restore a p53 transcriptome and target an S-phase cell cycle checkpoint in tumors with mutated-p53. (PubMed, Elife) - "CB002 and structural-analogs restore p53 signaling in tumors with mutant-p53 but we find that unlike other xanthines such as caffeine, pentoxifylline, and theophylline, they do not deregulate the G2 checkpoint. Preliminary in vivo studies demonstrate anti-tumor efficacy in mice. Thus, a novel class of anti-cancer drugs shows the activation of p53 pathway signaling in tumors with mutated p53, and targets an S-phase checkpoint."

Journal • Oncology • CCNA2 • RPA2 • TP53

First report: Co-infection of Sarcococca hookeriana (sweetbox) by Coccinonectria pachysandricola and Calonectria pseudonaviculata causes a foliar disease of sweetbox in Pennsylvania. (PubMed, Plant Dis) - "BLASTn comparisons against NCBI GenBank revealed JAC 18-61 sequences (MT318150 and MT328399) shared 100% identity with Cps sequences (JX535321 and JX535307 from isolate CB002)...This is also the first report of co-infection of Cpa and Cps on diseased sweetbox foliage. Given the capacity of Cpa to infect both sweetbox and boxwood, inspection for Cpa on both hosts is advisable."

Journal

[VIRTUAL] A subgroup of potent CB002 xanthine derivatives define a novel class of anti-cancer drugs that restore the p53 pathway in tumors with mutated p53 and target an S-phase checkpoint (AACR-II 2020) - "In addition, our cell cycle analysis data in synchronized SW480 cells treated with etoposide suggests that CB002 and its analogs perturb the S-phase of the cell cycle and do not deregulate the G2 checkpoint. We are evaluating the benefit of synthetic lethality of these analogs in BRCA-deficient cell lines, focusing on target identification, determining the proteomic changes and in vivo efficacy of our p53-pathway restoring CB002 xanthine analogs. Taken together, our data suggests that CB002 and its potent xanthine analogs may provide a unique therapeutic strategy that can be clinically translated."

Oncology • ATR • BRCA • CCNE1 • CHEK1 • CHEK2

CB002, a novel p53 tumor suppressor pathway-restoring small molecule induces tumor cell death through the pro-apoptotic protein NOXA. (PubMed, Cell Cycle) - "R175H p53 expression was rescued by addition of proteasome inhibitor MG132 to CB002, suggesting a role for ubiquitin-mediated degradation of the mutant protein. In summary, CB002, a p53 pathway-restoring compound that targets mutant p53 for degradation and induces tumor cell death through NOXA, may be further developed as a cancer therapeutic."

Journal • PARP Biomarker

Newly identified p53-pathway restoring small molecule, CB002 analog #4 induces apoptosis and appears non-toxic in vivo (AACR 2019) - "We are investigating the in vivo efficacy of analog #4 in addition to its mechanism of action through micro-array experiments. Our data supports the concept that small molecules can restore the p53-pathway as a therapeutic strategy that can be translated into a clinical setting."

Preclinical