ADC payloads (auristatin, exatecan, maytansinoid)

Mechanism

항체에 붙은 payload는 리소좀에서 링커가 끊긴 뒤 세포독성 워헤드로 방출됩니다. MMAE/MMAF는 미세소관 중합을 막고, DM1/DM4는 메이탄시노이드 미세소관 저해제, DXd·SN-38은 TOP1 저해제입니다. 막투과성(bystander)이 고형암 균질성에 중요합니다.

Medicinal chemistry

MMAE는 dolastatin 10 유도체(valine-dil-dap-doll-norephedrine). DXd는 엑사테칸 유도체로 자가희생 링커와 짧은 반감기를 가집니다. DM1은 메이탄신 C3 에스테르에 티올 핸들이 있습니다. 링커(Val-Cit, SMCC, GGFC)가 방출 속도와 전신 독성을 결정합니다.

Structure families

• SN-38 / irinotecan (TOP1) small-molecule series7 compounds
• MMAE (auristatin) payload family12 compounds
• Exatecan / DXd (TOP1 inhibitor) payload family12 compounds
• DM1 / maytansinoid payload family9 compounds
• PBD dimer ADC payload family6 compounds
• Calicheamicin enediyne payload family6 compounds
• Duocarmycin CPI ADC payload series6 compounds

Key drugs · payloads

• DM1 (mertansine)Payload
• DXd (deruxtecan payload)Payload
• MMAE (monomethyl auristatin E)Payload
• Calicheamicin γ¹Payload
• DM4 (soravtansine)Payload
• Duocarmycin SAPayload
• ExatecanDrug
• Irinotecan (CPT-11)Drug
• MMAF (monomethyl auristatin F)Payload
• N-acetyl-γ-calicheamicinPayload
• Rubitecan (oral TOP1)Drug
• Seco-duocarmycinPayload
• SG3199 (PBD dimer warhead)Payload
• SN-38 (active metabolite)Drug
• SN-38 (irinotecan active)Drug
• SN-38 ADC linker-payload designPayload
• SN-38 payload (cross-family)Payload
• Tesirine (SG3249)Payload
• Topotecan (Hycamtin)Drug

Comparisons · briefs

• ADC payload 비교 — MMAE vs DXd vs DM1Comparison

BioMoa