CAJ | 학술논문

天然产物及其衍生物是药物的重要来源。Carfilzomib 是一个以天然产物为先导通过结构优化得到的用于治疗多发性骨髓瘤的药物，其先导化合物 Epoxomicin 是从微生物中发现的具有抗癌活性的环氧酮肽类天然产物，能够选择性地抑制蛋白酶体，其环氧酮结构以独特的两步反应和蛋白酶体共价结合，因此克服了同类药物的脱靶缺点。以 Epoxomi-cin 为先导，通过结构优化得到活性更强、成药性性更好的 Carfilzomib，作为新一代蛋白酶体抑制剂于2012年上市。
천연산물급기연생물시약물적중요래원。Carfilzomib 시일개이천연산물위선도통과결구우화득도적용우치료다발성골수류적약물，기선도화합물 Epoxomicin 시종미생물중발현적구유항암활성적배양동태류천연산물，능구선택성지억제단백매체，기배양동결구이독특적량보반응화단백매체공개결합，인차극복료동류약물적탈파결점。이 Epoxomi-cin 위선도，통과결구우화득도활성경강、성약성성경호적 Carfilzomib，작위신일대단백매체억제제우2012년상시。
Natural products and their derivatives have been invaluable as a source of therapeutic agents. Carfilzomib,a potential chemotherapy drug for patients with multiple myeloma,was developed from a microbial natural product Epoxomicin. Epoxomicin was found to exhibit potent anti - cancer activity,which might attribute to its inhibitory activity against proteasome. Because of its unique two- step binding mode,Epoxomicin has a clear advantage compared to other proteasome inhibitors with their substantial off - target activi-ty. With a more pontecy and better drug - like properties,Carfilzomib was developed from the lead compound Epoxomicin and approved by FDA as a second - generation proteasome inhibitor in 2012.