Аватромбопаг малеат

Description

Avatrombopag maleate is the maleate salt of avatrombopag, an oral small molecule thrombopoietin receptor (TPO-R, c-Mpl) agonist. Belongs to the class of non-peptide thrombopoietin receptor agonists. In chemical databases, the full name includes a fragment of (Z)-but-2-enedioic (maleic) acid and a complex thiazole-piperidine skeleton of the active substance. CAS 677007-74-8, UNII GDW7M2P1IS, NCI thesaurus code C142941, Anatomical Therapeutic Chemical Classification (ATC) code B02BX.

Basic Attributes

• CAS No: 677007-74-8
• Chemical Formula: C33H38Cl2N6O7S2
• Molecular weight: 765.72700
• Exact weight: 764.1620453
• UNII: GDW7M2P1IS
• NCI Thesaurus Code: C142941
• ATX code: B02BX
• PSA Specifications: 236.47000
• XLogP3: 6.74510

Substance class and mechanism of action

Avatrombopag, an oral thrombopoietin receptor agonist, binds to the transmembrane domain of the TPO-R receptor (c-Mpl) on the surface of megakaryocytes and their progenitor cells in the bone marrow, at a site different from the binding site of endogenous thrombopoietin, and therefore does not compete with it for the receptor. Binding triggers intracellular signaling that recapitulates the biological effects of thrombopoietin and stimulates megakaryocyte maturation and platelet production by the bone marrow.

Scope of application

• treatment of thrombocytopenia in adults with chronic liver disease before an elective medical or dental procedure
• treatment of chronic immune thrombocytopenia (ITP) in adults with insufficient response to previous treatment
• potential use for thrombocytopenia of various etiologies in acute and chronic dosage regimens

The anatomical-therapeutic-chemical classification code B02BX (other systemic hemostatics) reflects the substance’s belonging to the group of drugs that affect the blood coagulation system through stimulation of thrombocytopoiesis.

Advantages

Direct stimulation of normal production of new platelets by the bone marrow makes avatrombopag potentially useful for thrombocytopenia of a wide range of causes in a variety of patient populations, both when used briefly before procedures and during long-term chronic therapy.

Storage and handling

As an active pharmaceutical substance, avatrombopag maleate is stored and transported according to GMP requirements: sealed containers, protection from moisture and light, controlled temperature at all stages of the supply chain, full batch documentation.

Difference from other thrombopoietin receptor agonists

Unlike earlier non-peptide thrombopoietin receptor agonists, avatrombopag binds to a different part of the transmembrane domain of the receptor, which allows its action to be combined with the action of the endogenous hormone without competitive displacement. The molecule is characterized by high lipophilicity (XLogP3 6.74510) and a large polar surface area (PSA 236.47000), which is typical for complex heterocyclic drug substances with multiple binding sites.