186256-69-9

Basic information

• Product Name: [3S-(3alpha,10beta,13E,16beta)]-16-[3(S)-Chloro-2(R)-hydroxy-1(R)-methyl-3-phenylpropyl]-10-(3-chloro-4-methoxybenzyl)-3-isobutyl-6,6-dimethyl-1,4-dioxa-8,11-diazacyclohexadec-13-ene-2,5,9,12-tetraone
• Synonyms: Cryptophycin 55
• CAS NO: 186256-69-9
• Molecular Formula: C₃₆H₄₆Cl₂N₂O₈
• Molecular Weight: 705.68262
• Mol File: 186256-69-9.mol
• Article Data: 2

Chemical Properties

• CAS DataBase Reference: [3S-(3alpha,10beta,13E,16beta)]-16-[3(S)-Chloro-2(R)-hydroxy-1(R)-methyl-3-phenylpropyl]-10-(3-chloro-4-methoxybenzyl)-3-isobutyl-6,6-dimethyl-1,4-dioxa-8,11-diazacyclohexadec-13-ene-2,5,9,12-tetraone(CAS DataBase Reference)
• NIST Chemistry Reference: [3S-(3alpha,10beta,13E,16beta)]-16-[3(S)-Chloro-2(R)-hydroxy-1(R)-methyl-3-phenylpropyl]-10-(3-chloro-4-methoxybenzyl)-3-isobutyl-6,6-dimethyl-1,4-dioxa-8,11-diazacyclohexadec-13-ene-2,5,9,12-tetraone(186256-69-9)
• EPA Substance Registry System: [3S-(3alpha,10beta,13E,16beta)]-16-[3(S)-Chloro-2(R)-hydroxy-1(R)-methyl-3-phenylpropyl]-10-(3-chloro-4-methoxybenzyl)-3-isobutyl-6,6-dimethyl-1,4-dioxa-8,11-diazacyclohexadec-13-ene-2,5,9,12-tetraone(186256-69-9)

Safety Data

• Hazardous Substances Data: 186256-69-9(Hazardous Substances Data)

Upstream product

• 208581-45-7 (E)-5-(4-methoxyphenylmethyloxy)-2-methyl-2-pentenol 
• 208581-53-7 (E)-ethyl 5-(4-methoxyphenylmethyloxy)-2-methyl-2-pentenoate 
• 186256-68-8 cryptophycin 53 
• 866343-66-0 (S)-2-{3-[(R)-2-tert-Butoxycarbonylamino-3-(3-chloro-4-methoxy-phenyl)-propionylamino]-2,2-dimethyl-propionyloxy}-4-methyl-pentanoic acid 
• 162465-33-0 allyl (2S)-2-Hydroxy-4-methylpentanoate 
• 13748-90-8 (S)-2-hydroxyl-3,3-dimethylbutyric acid 
• 195387-08-7 methyl 3-<<(tert-butoxy)carbonyl>amino>-2,2-dimethylpropanoate 
• 162465-45-4 (R)-2-((tet-butoxycarbonyl)amino)-3-(3-chloro-4-methoxyphenyl)propanoic acid 
• 162465-44-3 methyl (2R)-2-[(tert-butoxycarbonyl)amino]-3-(3-chloro-4-methoxyphenyl)propanoate 
• 478183-57-2 (2R)-2-[(tert-butoxycarbonyl)amino]-3-(3-chloro-4-hydroxyphenyl)propanoic acid 
• 556-02-5 tyrosine 

Relevant articles and documents

Cryptophycin-55/52 based antibody-drug conjugates: Synthesis, efficacy, and mode of action studies

Cryptophycin-52 (CR52), a tubulin inhibitor, exhibits promising antitumor activity in vitro (picomolar level) and in mouse xenograft models. However, the narrow therapeutic window in clinical trials limits its further development. Antibody-drug conjugate (ADC), formed by coupling cytotoxic compound (payload) to an antibody via a linker, can deliver drug to tumor locations in a targeted manner by antibody, enhancing the therapeutic effects and reducing toxic and side effects. In this study, we aim to explore the possibility of CR52-based ADC for tumor targeted therapy. Due to the lack of a coupling site in CR52, its prodrug cryptophycin-55 (CR55) containing a free hydroxyl was synthesized and conjugated to the model antibody trastuzumab (anti-HER2 antibody drug approved by FDA for breast cancer therapy) via the linkers based on Mc-NHS and Mc-Val-Cit-PAB-PNP. The average drug-to-antibody ratios (DARs) of trastuzumab-CR55 conjugates (named T-L1-CR55, T-L2-CR55, and T-L3-CR55) were 3.50, 3.29, and 3.35, respectively. These conjugates exhibited potent cytotoxicity in HER2-positive tumor cell lines with IC50 values at low nanomolar levels (0.58–1.19 nM). Further, they displayed significant antitumor activities at the doses of 10 mg/kg in established ovarian cancer (SKOV3) and gastric cancer (NCI–N87) xenograft models without overt toxicities. Finally, the drug releases were analyzed and the results indicated that T-L3-CR55 was able to effectively release CR55 and further epoxidized to CR52, which may be responsible for its best performance in antitumor activities. In conclusion, our results demonstrated that these conjugates have the potential for tumor targeted therapy, which provides insights to further research the CR55/CR52-based ADC for tumor therapy.