Source 1primary paper2020Future Drug Discovery
Toolkit/photoswitchable diarylethene-containing gramicidin S analogs
photoswitchable diarylethene-containing gramicidin S analogs
Also known as: photoisomeric forms of photoswitchable diarylethene-containing analogs
Taxonomy: Mechanism Branch / Component. Workflows sit above the mechanism and technique branches rather than replacing them.
Summary
LD50 values for gramicidin S and photoisomeric forms of its photoswitchable diarylethene-containing analogs were determined using mice.
Usefulness & Problems
No literature-backed usefulness or problem-fit explainer has been materialized for this record yet.
Published Workflows
Peptide Drugs for Photopharmacology: How Much of a Safety Advantage Can Be Gained By Photocontrol?
2020Objective: To verify whether photocontrol of biological activity could augment safety of a chemotherapeutic agent.
Why it works: The study compares photoisomer-dependent in vitro activity with in vivo LD50 and then uses ADME testing to explain why in vivo toxicity differences do or do not track with in vitro potency differences.
photocontrol of biological activityphotoisomer-dependent activity differencesmouse LD50 determinationcell viability comparisonADME testing in a murine cancer model
Stages
- 1.Mouse LD50 determination(confirmatory_validation)
This stage directly measures whole-animal acute toxicity to test whether photocontrol improves safety.
Selection: Determine LD50 values for gramicidin S and photoisomeric forms of photoswitchable diarylethene-containing analogs in mice.
- 2.Cell viability comparison(secondary_characterization)
This stage provides an in vitro comparator for the same compounds so the authors can assess whether photoisomer-dependent cytotoxicity differences align with in vivo toxicity.
Selection: Compare mouse LD50 results with cell viability measurements for the same compounds.
- 3.ADME analysis in murine cancer model(functional_characterization)
This stage investigates whether pharmacokinetic behavior explains why in vivo LD50 differences are less pronounced than in vitro cytotoxicity differences.
Selection: Conduct ADME tests using a murine cancer model to understand the reasons for observed in vivo toxicity.
Taxonomy & Function
Primary hierarchy
Mechanism Branch
Component: A low-level protein part used inside a larger architecture that realizes a mechanism.
Techniques
No technique tags yet.
Target processes
No target processes tagged yet.
Input: Light
Validation
Cell-freeBacteriaMammalianMouseHumanTherapeuticIndep. Replication
Supporting Sources
Ranked Claims
Optimization of pharmacokinetic parameters of photoisomers is an important issue in developing photopharmacological drugs.
Nevertheless, optimization of the pharmacokinetic parameters of photoisomers is an important issue to be addressed during the development of photopharmacological drugs.
Substantial differences in in vitro cytotoxicity between photoisomers translated into less pronounced differences in mouse LD50 because of unfavorable pharmacokinetic parameters.
While in vitro cytotoxicity values of the photoisomers differed substantially, the differences in the observed LD50 values were less pronounced due to unfavorable pharmacokinetic parameters.
Photocontrol of biological activity can provide an overall safety-profile advantage for a chemotherapeutic agent.
Conclusion: Despite unfavorable pharmacokinetic properties as in the representative case studied here, there is an overall advantage to be gained in the safety profile of a chemotherapeutic agent via photocontrol.
Approval Evidence
1 source3 linked approval claimsfirst-pass slug photoswitchable-diarylethene-containing-gramicidin-s-analogs
LD50 values for gramicidin S and photoisomeric forms of its photoswitchable diarylethene-containing analogs were determined using mice.
Source:
development requirementsupports
Optimization of pharmacokinetic parameters of photoisomers is an important issue in developing photopharmacological drugs.
Nevertheless, optimization of the pharmacokinetic parameters of photoisomers is an important issue to be addressed during the development of photopharmacological drugs.
Source:
in vitro in vivo translation limitsupports
Substantial differences in in vitro cytotoxicity between photoisomers translated into less pronounced differences in mouse LD50 because of unfavorable pharmacokinetic parameters.
While in vitro cytotoxicity values of the photoisomers differed substantially, the differences in the observed LD50 values were less pronounced due to unfavorable pharmacokinetic parameters.
Source:
safety advantagesupports
Photocontrol of biological activity can provide an overall safety-profile advantage for a chemotherapeutic agent.
Conclusion: Despite unfavorable pharmacokinetic properties as in the representative case studied here, there is an overall advantage to be gained in the safety profile of a chemotherapeutic agent via photocontrol.
Source:
Comparisons
No literature-backed comparison notes have been materialized for this record yet.
Ranked Citations
- 1.