RXR Agonists

No Image

OADs with significant Cardio-protective benefits, improving whole body insulin sensitivity with improvement in muscle endurance.

Connexios’ program comprises unique and selective rexinoid agonists with Pan-PPAR activation across multiple tissues with a clean demonstrated safety profile. The lead candidate has been shown to regulate multiple target genes through selected heterodimer partners, resulting in widespread physiological benefits

Retinoid X Receptor (RXR) functions as a heterodimeric partner to several other nuclear receptors and regulates intracellular receptor signaling pathways involved in, among others, glucose and lipid metabolism and therefore has potential to impact multiple risk factors associated with the metabolic syndrome. Selective activation of RXR heterodimers can address critical dysregulations that underlie cellular pathology in key tissues observed in T2DM and metabolic syndrome.

As a potent agonist of RXR isoforms α, β and γ, CNX-013-B2 transactivates the three PPAR isoforms α, β and γ but yet does not carry any of the safety risks associated with these nuclear receptors that have plagued many of the previous programs. The crucial benefits shown by this compound in various disease models:

  • Significant improvement in fasting and post-prandial hyperglycemia.
  • Steep reduction of HbA1c.
  • Improvement in whole body insulin sensitivity without weight gain.
  • Excellent control of various lipid parameters and liver steatosis.
  • Significant improvement in muscle endurance.
  • No hypertriglyceridemia, hepatomegaly, hypothyroidism, fluid retention and edema and increase in bone marrow adiposity.

RXR is a known target for cancer, but few groups have demonstrated its role in lipid metabolism and the likely benefits conferred by activating its specific herterotrimeric partners across key tissues.  With its strong control on Diabetic dyslipidemia and direct cardiovascular benefits, these candidates can yield therapies which are likely to be very valuable addition to a clinician’s armamentarium in the management of advanced diabetes.

Well qualified lead ready to enter IND enabling studies.

Key Result:

CNX-013-B2 reduced aortic fatty streaks, foam cell accumulation and VCAM expression in high cholesterol diet induced hamster model of dyslipidemia and thus provide cardiovascular benefits

RX-B2: Tread Mill Test