Posted on by biozimmer

Our Science

ADRESSING HIGH POTENTIAL BUT CHALLENGING DRUG TARGETS

While the clinical success of tyrosine kinase inhibitors has validated the power of targeted therapies, numerous well-described oncogenic drivers are still not addressed by approved medicines. A key reason is their dependence on challenging protein–protein interactions (PPIs), which have historically been difficult to modulate with small molecules.

ULTRA-PRECISE TARGETING OF A DISEASE-DRIVING MECHANISM

STAT5 is one such target. In hematologic malignancies, including acute myeloid leukemia (AML), oncogenic STAT5 signaling is driven by oligomerization, while STAT5 dimerization is essential for its normal cellular function. Effective therapeutic intervention therefore requires highly selective targeting of STAT5 oligomerization without disrupting physiological STAT5 activity. See our publications for further information.

STAT5 dimers are required for healthy blood cell development. Hyperactivated STAT5 forms oligomers that drive oncogenic gene transcription.
Selective inhibition of STAT5 oligomerization by small molecules enables effective AML treatment while minimizing toxicity.
SMALL MOLECULES INHIBIT ABERRANT STAT5 OLIGOMERIZATION

RIANA Therapeutics was founded to address this challenge. We developed and protected a unique, cell-based phenotypic screening system that enables the identification of small-molecule inhibitors capable of selectively disrupting oncogenic PPIs.
Using this technology, we screened a chemical library and successfully identified STAT5 small molecule oligomerization inhibitors, which form the basis of RIANA’s first lead discovery program.
Our discovery platform integrates target-driven biology, structure-guided medicinal chemistry, and rigorous functional validation. By starting from a well-validated disease mechanism and advancing through iterative design and testing, we aim to generate highly selective small molecules that directly modulate STAT5 function in cancer cells.

TARGETING STAT5 WITH SMALL MOLECULES: FIRST-IN-CLASS THERAPIES, HIGHLY EFFECTIVE WITH LOW SIDE-EFFECTS

Targeting oncogenic STAT5 oligomerization represents a novel and highly innovative therapeutic strategy. Due to the intrinsic selectivity of this approach, we expect to achieve potent anti-cancer activity with significantly reduced side effects, while maintaining adequate efficacy. Through this strategy, RIANA Therapeutics seeks to expand the druggable landscape and deliver first-in-class therapies for patients with high unmet medical need, beginning with acute myeloid leukemia.