Mavacamten

Mechanism of Action

Myosin is a family of enzymes that can produce mechanical output by an ATP-mediated cyclic interaction with actin. When ATP is bound to the myosin head, it is hydrolyzed into ADP and organophosphate by myosin ATPase activity, and the energy produced from the reaction is stored in the myosin head. As the organophosphate dissociates from myosin, it shifts myosin into a strong binding state to actin, thus creating a myosin-actin complex otherwise known as "cross-bridging".2,3,5Dissociation of the organophosphate also causes a conformation change in myosin that creates strain in the actin-myosin bridge that can only be released once the actin and myosin filaments slide past each other, thus shortening the sarcomere and create a muscle contraction.5,9 Once the sliding is completed, ADP is released to create further movement of the myosin head.9 Although this ADP release-induced movement is minor and unlikely to contribute to the sarcomere movement, researchers have hypothesized that this movement is likely essential in limiting the sliding velocity of actin.6,7,8,9Finally, myosin then bind to a new ATP molecule to initiate the chemomechanical cycle again.

Mavacamten reduces sarcomere hypercontractility by acting as an allosteric and reversible modulator of the beta-cardiac isoform of myosin to reduce its ATPase activity, thus reducing actin-myosin cross bridging.4 Specifically, mavacamten inhibits the phosphate release, the cycle's rate-limiting step, without affecting the ADP release rate in actin-bound myosin.1Also, mavacamten inhibits binding of ADP-bound myosin to actin as well as ADP release to prime the myosin head to initiate turnover.3Recently, it was also discovered when myosin is not in its active state to interact with actin, it exists in equilibrium between 2 energy sparing states: a disordered relaxed state, where interaction between actin and myosin by the thin filament regulatory proteins, and a super relaxed state, where significant myosin head-to-head interaction lengthen ATP turnover rate.10,11. Mavacamten's binding to myosin can shift the equilibrium toward the super relaxed state, effectively exerting both a basal and actin-activated ATP inhibition

Indication

Mavacamten is indicated for the treatment of adults with symptomatic New York Heart Association (NYHA) class II-III obstructive hypertrophic cardiomyopathy (HCM) to improve functional capacity and symptoms

Dr. Reddy’sの専門知識・技術

ハイデラバード（インド）に本社を構えるDr. Reddy’s Laboratoriesは、世界的に有名な原薬（API）供給業者です。Dr. Reddy’sのAPIビジネスは米国、ヨーロッパ、ブラジル、南米、日本、中国、韓国、その他の新興市場において製薬会社の推奨パートナーとなっています。

Dr. Reddy’sのAPIビジネスは、ステロイド、ペプチド、複合長鎖分子、高薬理活性API（HPAPI /腫瘍学薬）など、複合APIの開発・製造において、30年以上にわたり高度な技術的実績を築き上げ、成長しています。この専門知識・技術は弊社の知的財産および規制関連業務の実績と共に、一貫して規制基準を満たし、それを超える優れた価値を生み出しています。Dr. Reddyの(-) API, R&D (研究開発)、IP、規制の高度な専門知識・技能の結果です。

顧客が真っ先に市場に参入するのに重要な要素は、機敏な供給網です。弊社は全施設を効率的に、そしてコストを最適化して稼働させ、品質と安全性、また、生産性の最新基準に従うことで、そうした供給網を実現させます。オフィスと工場の結びつきを強化し、ダイナミックな市場の変化に迅速に対応しています。そうした理由から、弊社は不足を解消して突発的な供給を満たすことができるのです。