DBM operates as both a CRO and R&D company through CRO clinical research outsourcing. Learn more about our assets available for licensing opportunities below.
ADIPONECTIN SECRETAGOGUE LIGANDS R&D PROGRAM
DBM’s Adiponectin Secretagogue Ligands R&D program is currently profiling multiple hit-to-lead chemical series, termed DBM ADN hit-to-lead chemical classes, for type 2 diabetes mellitus, obesity, and diabetes and obesity-related complications. Key findings and attributes are highlighted below, with different human diseases that may be attacked by this therapeutic.
- Discovered and validated in differentiated human adipocytes (fat cells) from both subcutaneous and visceral depots and from normal and diseased donors with secreted adiponectin (ADN) as the primary endpoint in a targeted and phenotypic design
- Effective ‘potentiators’ of both total and higher molecular weight (HMW) adiponectin / production and secretion as measured by AlphaLISA (Perkin-Elmer), ELISA, and by Western blot analysis of culture supernatants
- Equivalent or near the efficacy/potency of the PPARgamma ligands or TZD drugs on adiponectin production and secretion
- MOA is independent from the PPARgamma pathway
- Compounds are effective for adiponectin production and secretion but do not influence leptin secretion
- No in vitro cytotoxicity is observed with any of the DBM ADN compounds, whereas the TZD drugs show in vitro cytotoxicity to human fat cells, kidney cells, and other cell types
- Early in vitro ADME profiles are clean for the 4 main hit-to-lead DBM ADN series, ADN1, ADN5, ADN12, and ADN18, now progressed to in vivo testing
- The maximum tolerated dose (MTD) of each hit-to-lead DBM ADN series, ADN1, ADN5, ADN12, and ADN18, is at least 100 mg/kg
- Each hit-to-lead DBM ADN series, ADN1, ADN5, ADN12, and ADN18, is being evaluated currently for potentiation of adiponectin production and secretion in vivo in normal and in diabetic, overweight and hypertensive ZSF-1 rats with a top-notch CRO. Early results show potentiation even in normal rats with already high levels of circulating adiponectin.
- Near maximal and sub-maximal doses of ‘best in class’ compounds from all 4 main series are being tested currently in vivo in ZSF-1 rats over 16 weeks for protection against diabetic nephropathy, protection against similar hyperglycemic injury in the heart, liver, eye, etc., and for therapeutic benefit for other diabetic, obese and hypertensive endpoints and for potentiation of adiponectin production and secretion in vivo.
The independent validation of the above findings will continue to emerge from the CRO that is executing the work in vivo in animal models of disease.
Please inquire if there is significant interest for both Top Level and Scientific slide decks for this program.
CFTR LIGANDS R&D PROGRAM
DBM’s CFTR Ligand R&D program is currently profiling the “CFTR Ligand 700 Series” to numerous and different human disease indications based upon its unique MOA influence on both the most common cystic fibrosis (CF) mutation, delF508 CFTR, and on wild-type CFTR. Key findings and attributes are highlighted below, with different human diseases that may be attacked by this therapeutic.
- Discovered and validated in human epithelial cell platforms endogenously expressing delF508-CFTR, the most common CF gene mutation and CFTR mutant, with the re-appearance of membrane halide permeability as the primary endpoint in a targeted and phenotypic design
- Effective ‘corrector’ of the ER retention folding defect in delF508-CFTR in human bronchial epithelial cell platforms – superior to VX-809, its analogs, and other such research tool compounds
- Potent and effective ‘potentiator’ of wild-type CFTR protein expression
- Modest ‘corrector’ or ‘potentiator’ of CFTR anion transport function
- Effective ‘inhibitor’ of hyperactive ENaC sodium transport function – Potent and effective ‘activator’ of the ‘CFTR signalsome’ or CFTR’s ability to regulate other ion transport proteins and other cellular processes and pathways – the Vertex drugs do not influence ENaC
- Potent and effective anti-proliferative compound – Causes cytostasis or growth arrest in primary cystic human ADPKD cells (grown in 3D and in 2D) and in >100 different human cancer cell lines
There has been independent validation of the above findings in independent laboratories (CROs, academic labs, industry labs) that were provided coded and blinded compounds for analysis.
Please inquire if there is significant interest for both Top Level and Scientific slide decks for this program.