Belzutifan Chemical Properties

Boiling point:

505.8±50.0 °C(Predicted)

Density 

1.56±0.1 g/cm3(Predicted)

storage temp. 

Store at -20°C, stored under nitrogen

solubility 

DMSO: 50 mg/mL (130.43 mM)

form 

Solid

pka

11.66±0.60(Predicted)

color 

White to light yellow

Belzutifan Usage And Synthesis

Description

Belzutifan is an orally active, small molecule inhibitor of hypoxia inducible factor (HIF)-2alpha (HIF-2a), with potential antineoplastic activity. The HIF-2α protein was a key player in the growth of certain cancers. Initially considered to be undruggable, a binding pocket was eventually discovered in the HIF-2α molecule which allowed for compounds to bind and inhibit these proteins. 

Uses

Belzutifan is a prescription medicine used to treat adults with von Hippel-Lindau (VHL) disease who need treatment for a type of kidney cancer called renal cell carcinoma (RCC), tumors in the brain and spinal cord called central nervous system hemangioblastomas, or a type of pancreatic cancer called pancreatic neuroendocrine tumors, that do not need surgery right away.

Indications

Belzutifan is indicated for the treatment of adult patients with von Hippel-Lindau (VHL) disease who require therapy for associated renal cell carcinoma (RCC), central nervous system (CNS) hemangioblastomas, or pancreatic neuroendocrine tumors (pNET), who do not require immediate surgery.

Mechanism of action

Belzutifan inhibits the complexation of HIF-2α with another transcription factor, HIF-1β, a necessary step in its activation - by preventing the formation of this complex, belzutifan can slow or stop the growth of VHL-associated tumors. Belzutifan received FDA approval for the treatment of select VHL-associated cancers on August 13, 2021.

Pharmacokinetics

Upon oral administration, belzutifan binds to and blocks the function of HIF-2alpha, thereby preventing HIF-2alpha heterodimerization and its subsequent binding to DNA. This results in decreased transcription and expression of HIF-2alpha downstream target genes, many of which regulate hypoxic signaling. This inhibits cell growth and survival of HIF-2alpha-expressing tumor cells. HIF-2alpha, the alpha subunit for the heterodimeric transcription factor HIF-2, is overexpressed in many cancers and promotes tumorigenesis.

Side effects

Side effects ofBelzutifan that was reported:
allergic reactions(skin rash,itchingorhives; swelling of the face, lips, or tongue)
blurred vision OR changes in vision
high blood sugar (increased hunger, thirst or urination; unusually weak or tired, blurry vision)
infection (fever, chills,cough,sore throat,pain;or trouble passing urine)
low calcium levels(fast heartbeat; muscle cramps or;pain;;pain, tingling, or numbness in the hands or feet; seizures)
low red blood cell counts (feeling faint; lightheaded, falls; unusually weak or tired)
trouble breathing
trouble passing urine or change in the amount of urine