Core expertise in molecularmodelling and drug discovery

GERO leverages proprietary computational drug discovery platform to design new drugs against challenging pharmacological targets. We work together with medical chemists and biologists from the key CROs, e.g. Wuxi, Nanosyn etc. Our company collaborates with the foremost investigators around the world: UCD, NYU, MIT, Texas Tech University, Drexel University etc.

GERO has an experience of technology licensing and drug discovery projects with biotech, Academia and pharma, including members of World Top 20, as well as dozens of projects.


Cancer Metabolism

Tumor cells are often highly metabolically active and switch from oxidative phosphorylation to a glycolytic phenotype. This helps reduce their reliance on mitochondria and avoid apoptosis. Some tumors have glycolytic rates up to 200 times that of normal and the glycolytic phenotype correlates with cancer aggressiveness, metastasis and drug resistance.

PFKFB3 is highly over-expressed and activated in most cancer cells, and is a key mechanism tumors use to switch to glycolysis. Our studies indicate that by inhibiting PFKFB3, tumor glycolytic metabolism can be overruled, leading to tumor control. There is evidence that inhibition of PFKFB3 also inhibits angiogenesis (proliferating stalk endothelial cells rely on glycolysis for ATP production) and also leads to immune activation (inhibition combined with chemotherapy leads to immune-activated tumor control).

We believe that our molecule is a best-in-class PFKFB3 inhibitor. Using our proprietary molecular modeling, we designed the molecule to not bind the ATP binding pocket, leading to a highly selective inhibitor with minimal off-target binding. Anti-tumor efficacy was demonstrated in several in vivo efficacy models and a 30 day, once daily non-GLP toxicity study confirms a wide therapeutic window.

We are developing a biomarker to select patients with high PFKFB3 expressing tumors in our clinical trials, enabling a rapid and cost effective clinical development path.

We are actively exploring partnership opportunities, as we move this molecule into first-in-man clinical trials.

Inhibition of PFKFB3to control cancer cell metabolism


Neuron cells most rely on oxidative phosphorylation to produce energy in the form of ATP. Being very sensitive to oxidative stress they redirect glucose to Pentose Phosphate Pathway to replenish NADPH(H+) required for GSH antioxidant system. This metabolic shunt requires that PFKFB3 is continuously degraded by the E3 ubiquitin ligase anaphase-promoting complex/cyclosome-Cdh1 (APC/C-Cdh1).

Excitotoxicity is one of the markers of neuronal damage and depletion in neurodegenerative pathologies of Alzheimer’s disease, Parkinson’s disease, motor neurons in Amyotrophic Lateral Sclerosis, and stroke

The mechanism of neuronal excitotoxicity involves inhibition of APC/C-Cdh1 and thus stabilisation of PFKFB3 in cytoplasm. This leads to increase of glycolysis rate and oxidative damage of neuron cells.

We have demonstrated that our PFKFB3 inhibitors protect cells from apoptotic death in a model of glutamate-induced excitotoxicity in culture of rat primary cortical neurons. The project is being developed in Quantum Pharmaceuticals (a company of GERO group).

Inhibition of PFKFB3to protect neurons


The activated insulin receptor phosphorylates various cellular substrates on tyrosine residues. These substrates include the insulin receptor substrate family (IRS-1, -2, -3, -4) and the adapter protein Shc, which is another substrate of the insulin receptor. Shc is an attractive new target in metabolism as Shc inhibition increases insulin sensitivity and glucose resistance. Shc knockout mice are lean, insulin sensitive, glucose tolerant, stress resistant and resistant to a high fat diet. Recent insights into Shc biology have revealed that these effects may be driven by activation of brown adipose tissue, a key thermogenic tissue with a well-established role in energy expenditure. Brown fat is especially abundant in newborns and its primary function is to generate body heat, taking calories from normal fat.

It was shown that ShcKO mice are more insulin sensitive and glucose tolerant than controls under standard conditions. ShcA is a novel and well-validated target for increasing insulin sensitivity in Type 2 diabetes condition.

GERO and BUTO BIOPHARMA have developed a first-in-class drug candidate targeting Shc to treat type 2 diabetes. The identified lead compounds selectively bind to human protein Shc and increase insulin sensitivity in vitro and in vivo. The developed compounds also showed excellent safety profile in vitro and in vivo.


Tomilov AA, Ramsey JJ, Hagopian K, et al. The Shc locus regulates insulin signaling and adiposity in mammals. Aging cell. 2011;10(1):55-65. doi:10.1111/j.1474-9726.2010.00641.x.

Tomilov A, Bettaieb A, Kim K, et al. Shc depletion stimulates brown fat activity in vivo and in vitro. Aging Cell. 2014;


FtsZ is a bacterial protein involved in cell division process. This protein is highly conserved among different species of bacteria and it was found in bacteria, archaebacteria and in the chloroplasts of some plants. FtsZ is a homolog of tubulin which presents in all eukaryotic cells and performs a similar function. As well as tubulin, it contains several possible pockets on surface that can bind potential inhibitors of FtsZ.

Bacterial cell division is the process in which a bacterial cell is split into two daughter cells. Usually, this process contains several consistent steps: replication of DNA, cell elongation, Z ring formation, septum formation and some others.

figure 1Reference: VOER

FtsZ protein is the major player in several steps of cell division. The dynamic process of polymerization and depolymerization of FtsZ provides Z-ring formation and contraction of the Z-ring. Also, this protein is widespread among bacteria and it is highly conserved among species. Taking into account the absence of FtsZ in the higher eukaryotes and its evolutionary distance from tubulin, FtsZ can be considered as an attractive target to develop potential antibacterial agents, that may cause selective toxicity to bacterial pathogens. Anti-MRSA activity of FtsZ inhibitors was shown in recent studies during in vitro and in vivo experiments.

Using a unique computational drug discovery platform GERO identified and studied several classes of chemical compounds with antibacterial activity (against strains of Staphylococcus aureus). The disruption of the normal FtsZ polymerization process by our compounds was shown to be dose-dependent in in vitro model (Figure 2A). Also our compounds cause morphological changes characteristic of FtsZ inhibitors (Figure 2B). B. subtilis and S. aureus experienced morphological changes nearly identical to well-known FtsZ inhibitor PC190723.

figure 2

Now we study structure-activity relationship, optimize pharmacological properties, pharmacokinetic and toxicological characteristics of identified compounds.


Antibiotic therapy is still the mainstay of medical care for bacterial infections, but antibiotic therapy is complicated by antibiotic resistance. Problem of the antibiotic resistance of the bacteria can be solved or by development of the new antibacterial agents, either by increasing of the efficiency of the existent classes of antibiotics.

Recently it has been shown,that bacteria-derived H2S correlates with resistance of Gram-negative and Gram-positive bacteria to antibiotics.

Two bacterial proteins cystathionine β-synthase (CBS) and cystathionine γ-lyase (CSE) inhibitors are responsible for H2S production in some bacterial species, including Pseudomonas aeruginosa or Staphylococcus aureus.

Inactivation these proteins suppresses H2S production, that lead to becoming pathogens highly sensitive to a multitude of antibiotics. Therefore, inhibitors of these targets should be considered as an augmentation therapy, that sensitise a broad range of pathogens to antibacterial treatment.

GERO and academic collaborators have identified lead compounds, and demonstrated preliminary efficacy of these compounds in in vitro and in vivo tests. The developed compounds have acceptable pharmacokinetic and toxicity properties. Now we study structure-activity relationship, optimize pharmacological properties, pharmacokinetic and toxicological characteristics of identified lead-compounds.


We are seeking pre-clinical research collaborations and early out-licensing opportunities.

For partnering and collaboration