paroxysmal

Iptacopan hydrochloride (LNP023 hydrochloride) is a small-molecule inhibitor and a complement factor B inhibitor (IC50 = 10 nM, KD = 7.9 nM) with high selectivity, oral activity, and cell permeability, used for the treatment of complement-mediated diseases including paroxysmal nocturnal hemoglobinuria, IgA nephropathy, and C3 glomerulopathy.

Etripamil (MSP-2017) displays atrioventricular nodal conduction and prolongs atrioventricular nodal refractory periods by inhibiting calcium ion influx through the calcium slow channels in the atrioventricular node cells. Etripamil is an antagonist of short-acting L-type calcium-channel. It has a rapid onset of action designed for intranasal administration. It is also used to treat Paroxysmal Supraventricular Tachycardia.

SR59230A hydrochloride (SR59230A HCl) is a blood-brain permeable, selective and highly potent β3-adrenergic receptor antagonist that inhibits ultradian brown adipose tissue thermogenesis and interrupts associated paroxysmal brain and body heating.

Etripamil (MSP-2017) hydrochloride is a fast-acting L-type calcium channel blocker used in the study of paroxysmal supraventricular tachycardia (PSVT). By inhibiting calcium ion influx through slow calcium channels, etripamil hydrochloride slows atrioventricular nodal conduction and extends the atrioventricular nodal refractory period.

Factor B-IN-7 (Compound (I)) is a selective inhibitor of Factor B. It disrupts the interaction between Factor B and C3b, thereby preventing excessive complement activation. Factor B-IN-7 holds potential for research into complement-mediated diseases such as paroxysmal nocturnal hemoglobinuria (PNH), C3 glomerulopathy, and age-related macular degeneration (AMD).

Flecainide is an orally administered antiarrhythmic agent acting as a sodium channel blocker and IKr inhibitor, indicated for the treatment of paroxysmal supraventricular tachycardia (PSVT).

Factor B-IN-8 (Compound (3R,4R)-15) is a potent, selective, and orally active inhibitor of Factor B, demonstrating an IC50 value of 10.2 nM. It effectively blocks the interaction between Factor B and C3b, thus preventing the formation of the C3 convertase (C3bBb). Additionally, Factor B-IN-8 hinders the deposition of the membrane attack complex (MAC) along the alternative pathway with an IC50 of 59.3 nM. This compound reduces the cleavage of Factor B protein and lessens the deposition of complement C3d in the glomeruli and renal tubules. Factor B-IN-8 is applicable in the research of arthritis and paroxysmal nocturnal hemoglobinuria (PNH).

Ravulizumab (ALXN1210) is a humanized monoclonal antibody that specifically binds to human complement protein C5 with high affinity, targeting complement factor 5 to block complement activation. It can be used for the prevention and treatment of paroxysmal nocturnal hemoglobinuria, atypical hemolytic uremic syndrome, and myasthenia gravis.

Crovalimab (SKY59; RO7112689) is an Fc-engineered and pH-dependent humanised monoclonal antibody that binds to complement C5 and blocks its cleavage into C5a and C5b, thereby inhibiting MAC formation and intravascular haemolysis. It can rebind to the FcRn receptor under acidic pH conditions and return to the bloodstream, making it suitable for the treatment of paroxysmal nocturnal haemoglobinuria (PNH).

Danicopan (ACH-4471) (ACH-4471) is a selective, orally active small molecule factor D inhibitor with high binding affinity to human factor D, with a Kd value of 0.54 nM. Danicopan (ACH-4471) inhibits the activity of the complement replacement pathway (APC) and may block the complement replacement pathway in paroxysmal nocturnal hemoglobinuria (PNH) and atypical hemolytic uremic syndrome (aHUS).