
The Programs
Building a pipeline backed by validated science and long-standing expertise in small molecule drug discovery

Driving Cellular Function
Natural biological networks or pathways signal to cells to perform essential operations to maintain order and efficiency in the body. When those networks become impaired by age, disease or genetic mutations, cells no longer function as they should.
Cells are sophisticated structures equipped with specific functions that help to maintain order and efficiency in the body. Cellular function is maintained in part by natural biological networks that orchestrate pathways involved in the regulation of lysosomal biogenesis and autophagy, critical processes for removing cellular waste. Nutrient sensing also contributes to how cells respond. In fact, nutrient sensing can become dysregulated with age and disease – contributing to disease by affecting the processes that convert nutrients to energy which are essential for cell survival.
Generian is amplifying (or boosting) the intrinsic activity of the body’s natural signaling networks to improve cellular function treating and ultimately, reversing the course of disease.
Targets that Matter
Leveraging decades of research from some of the foremost experts in age-related diseases and E3 ligase biology, Generian has identified novel therapeutic intervention strategies to modulate the activity of network regulators (TFEB and AMPK) which are validated therapeutic targets essential to cellular function that diminish with age, disease or genetic mutations.

TARGET: TFEB
TFEB (or Transcription Factor EB) plays an essential role in cellular quality control by regulating autophagy and lysosomal biogenesis. TFEB augments clearance of intracellular aggregates, damaged organelles and granules, and extracellular material. This makes it a potential therapeutic target for diseases of protein or lipid aggregation, impaired quality control, and defective pathogen clearance including:
- Lysosomal storage diseases
- Pancreatitis
- IBD and Crohn’s disease
- CNS Proteopathies (Parkinson’s disease, Lewy body dementia)
- Dry AMD

TARGET: AMPK
AMPK (or AMP-activated protein kinase) helps to maintain cellular fitness, playing an essential role in nutrient sensing and appropriate cell metabolism. AMPK’s role as a key regulator of several metabolic pathways make it a potential therapeutic target for treating diseases of impaired energy metabolism, including:
- Primary renal disease
- Myotonic Dystrophy Type 1
- Diabetic nephropathy/NASH
- Primary mitochondrial diseases
Key TFEB Studies
Autophagy gone awry in neurodegenerative diseases
Learn More
A gene network regulating lysosomal biogenesis and function
Learn More
TFEB Links Autophagy to Lysosomal Biogenesis
Learn More
TFEB dysregulation as a driver of autophagy dysfunction in neurodegenerative disease: Molecular mechanisms, cellular processes, and emerging therapeutic opportunities
Learn More
TFEB-mediated autophagy rescues midbrain dopamine neurons from α-synuclein toxicity
Learn More
Transcriptional Activation of Lysosomal Exocytosis Promotes Cellular Clearance
Learn More
Selective clearance of aberrant tau proteins and rescue of neurotoxicity by transcription factor EB
Learn More
Key AMPK Studies
A Fbxo48 inhibitor prevents pAMPKα degradation and ameliorates insulin resistance
Learn More
Activating AMP-activated protein kinase (AMPK) slows renal cystogenesis
Learn More
AMP-activated/SNF1 protein kinases: conserved guardians of cellular energy
Learn More
AMPK: guardian of metabolism and mitochondrial homeostasis
Learn More
Targeting deregulated AMPK/mTORC1 pathways improves muscle function in myotonic dystrophy type I
Learn More
Role of AMP-activated protein kinase in kidney tubular transport, metabolism, and disease
Learn More
Treatment of nonalcoholic fatty liver disease: role of AMPK
Learn More
AMP-activated protein kinase: the current landscape for drug development
Learn More