May 14, 2023

Public workspaceABT263 (Navitoclax) Treatment in Mice

DOI
dx.doi.org/10.17504/protocols.io.5jyl8j4r6g2w/v1
  • 1Sanford Burnham Prebys Medical Discovery Institute;
  • 2Adams Lab
  • Peter Adams: PI of Adams Lab and NIH grant awardee;
Andrew Davis
Icon indicating open access to content
QR code linking to this content
DOI: dx.doi.org/10.17504/protocols.io.5jyl8j4r6g2w/v1
Protocol Citation: Andrew Davis, Peter Adams 2023. ABT263 (Navitoclax) Treatment in Mice. protocols.io https://dx.doi.org/10.17504/protocols.io.5jyl8j4r6g2w/v1
License: This is an open access protocol distributed under the terms of the Creative Commons Attribution License,  which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited
Protocol status: In development
We are still developing and optimizing this protocol.
Created: May 12, 2023
Last Modified: May 14, 2023
Protocol Integer ID: 81804
Keywords: ABT263, Navitoclax, Mice, Oral Gavage
Funders Acknowledgement:
NIH
Grant ID: 1U54AG079758-01
Abstract
This protocol is for treating mice with the senolytic, Navitoclax, by oral gavage.
Materials
ABT263 (Navitoclax) from SelleckChem (cat no S1001)
Phosal 50PG from Fisher Scientific (cat no 502029444)
PEG400 from Fisher Scientific (cat no 502029444)
Ethanol 200 proof from VWR (cat no 71006-012 (EA))
Feeding Needle for Oral Gavage 20G x 38mm (2mm Tip) Curved from Pet Surgical (cat no DAFN2038C)

Vehicle is made as a solution of 60% Phosal 50PG, 30% PEG400, 10% Ethanol by volume. Phosal 50PG and PEG400 are very viscous and so may require extra time, heat, and/or positive displacement pipets to effectively move and mix. Dissolution of ABT263 in the vehicle requires heat (50-60°C ideally with shaking) and can be aided by sonication. Drug can be dissolved in the vehicle at 12.5mg/ml (100mg in 8ml vehicle). We did not test other concentrations.
Safety warnings
Always use recommended PPE from your institutional safety department (lab coat, gloves, eye protection, masks, etc.). This can also help to prevent contamination of your samples.
Ethics statement
All experiments using mice should be first approved by the appropriate oversight organization of your locale.
Before start
ABT263 must first be dissolved in the vehicle by heating to 60°C. Sonication can be used to dissolve faster. See the materials section for specifics.
Give mice Navitoclax or Vehicle by oral gavage at 50mg/kg/day. Mice receive vehicle or drug for a total of 14 days, spread across 6 weeks, as outlined in the sub-steps below.
Mice receive seven days of once-daily oral gavage of drug or vehicle
Then fourteen days with no treatment
Then seven more days of once-daily oral gavage of drug or vehicle
Then fourteen days with no treatment
Harvest tissues after the last day of no treatment
Protocol references
This protocol is adapted from the protocol in: Chang J, Wang Y, Shao L, Laberge RM, Demaria M, Campisi J, Janakiraman K, Sharpless NE, Ding S, Feng W, Luo Y, Wang X, Aykin-Burns N, Krager K, Ponnappan U, Hauer-Jensen M, Meng A, Zhou D. Clearance of senescent cells by ABT263 rejuvenates aged hematopoietic stem cells in mice. Nat Med. 2016 Jan;22(1):78-83. doi: 10.1038/nm.4010. Epub 2015 Dec 14. PMID: 26657143; PMCID: PMC4762215. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4762215/