PMID- 35807495
OWN - NLM
STAT- MEDLINE
DCOM- 20220712
LR  - 20220803
IS  - 1420-3049 (Electronic)
IS  - 1420-3049 (Linking)
VI  - 27
IP  - 13
DP  - 2022 Jul 1
TI  - In Vivo Evaluation of (-)-Zampanolide Demonstrates Potent and Persistent 
      Antitumor Efficacy When Targeted to the Tumor Site.
LID - 10.3390/molecules27134244 [doi]
LID - 4244
AB  - Microtubule-stabilizing agents (MSAs) are a class of compounds used in the 
      treatment of triple-negative breast cancer (TNBC), a subtype of breast cancer 
      where chemotherapy remains the standard-of-care for patients. Taxanes like 
      paclitaxel and docetaxel have demonstrated efficacy against TNBC in the clinic, 
      however new classes of MSAs need to be identified due to the rise of taxane 
      resistance in patients. (-)-Zampanolide is a covalent microtubule stabilizer that 
      can circumvent taxane resistance in vitro but has not been evaluated for in vivo 
      antitumor efficacy. Here, we determine that (-)-zampanolide has similar potency 
      and efficacy to paclitaxel in TNBC cell lines, but is significantly more 
      persistent due to its covalent binding. We also provide the first reported in 
      vivo antitumor evaluation of (-)-zampanolide where we determine that it has 
      potent and persistent antitumor efficacy when delivered intratumorally. Future 
      work on zampanolide to further evaluate its pharmacophore and determine ways to 
      improve its systemic therapeutic window would make this compound a potential 
      candidate for clinical development through its ability to circumvent 
      taxane-resistance mechanisms.
FAU - Takahashi-Ruiz, Leila
AU  - Takahashi-Ruiz L
AUID- ORCID: 0000-0003-1814-6465
AD  - Department of Pharmacology, Mays Cancer Center, University of Texas Health 
      Science Center San Antonio, San Antonio, TX 78229, USA.
FAU - Morris, Joseph D
AU  - Morris JD
AUID- ORCID: 0000-0001-5218-425X
AD  - Department of Natural Sciences and Mathematics, Dominican University of 
      California, San Rafael, CA 94901, USA.
FAU - Crews, Phillip
AU  - Crews P
AUID- ORCID: 0000-0002-9061-9549
AD  - Department of Chemistry and Biochemistry, University of California Santa Cruz, 
      Santa Cruz, CA 95064, USA.
FAU - Johnson, Tyler A
AU  - Johnson TA
AD  - Department of Natural Sciences and Mathematics, Dominican University of 
      California, San Rafael, CA 94901, USA.
FAU - Risinger, April L
AU  - Risinger AL
AUID- ORCID: 0000-0002-4363-3268
AD  - Department of Pharmacology, Mays Cancer Center, University of Texas Health 
      Science Center San Antonio, San Antonio, TX 78229, USA.
LA  - eng
GR  - R01 CA219948/CA/NCI NIH HHS/United States
GR  - CA219948/CA/NCI NIH HHS/United States
GR  - Endowment Fund/Fletcher Jones Foundation/
PT  - Journal Article
DEP - 20220701
PL  - Switzerland
TA  - Molecules
JT  - Molecules (Basel, Switzerland)
JID - 100964009
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Macrolides)
RN  - 0 (zampanolide)
RN  - P88XT4IS4D (Paclitaxel)
SB  - IM
MH  - *Antineoplastic Agents/chemistry
MH  - Cell Line, Tumor
MH  - Humans
MH  - Macrolides/chemistry
MH  - Microtubules/metabolism
MH  - Paclitaxel/chemistry
MH  - *Triple Negative Breast Neoplasms/drug therapy/metabolism
PMC - PMC9268097
OTO - NOTNLM
OT  - covalent
OT  - microtubule stabilizers
OT  - paclitaxel
OT  - triple-negative breast cancer
OT  - zampanolide
COIS- The authors declare no conflict of interest. The funders had no role in the 
      design of the study; in the collection, analyses, or interpretation of data; in 
      the writing of the manuscript, or in the decision to publish the results.
EDAT- 2022/07/10 06:00
MHDA- 2022/07/14 06:00
PMCR- 2022/07/01
CRDT- 2022/07/09 01:19
PHST- 2022/05/16 00:00 [received]
PHST- 2022/06/27 00:00 [revised]
PHST- 2022/06/29 00:00 [accepted]
PHST- 2022/07/09 01:19 [entrez]
PHST- 2022/07/10 06:00 [pubmed]
PHST- 2022/07/14 06:00 [medline]
PHST- 2022/07/01 00:00 [pmc-release]
AID - molecules27134244 [pii]
AID - molecules-27-04244 [pii]
AID - 10.3390/molecules27134244 [doi]
PST - epublish
SO  - Molecules. 2022 Jul 1;27(13):4244. doi: 10.3390/molecules27134244.