Classification of targets
The proposed classification follows: Angew. Chem. Int. Ed. 2016, 55, 10978–10999
Light-delivery is a guiding principle for the practicality of the photopharmacological approach:
Class 1: easy accessible: skin, eyes (ophthalmoscopy)
Class 2: accessible by endoscopy: GI tract, mouth and throat, sinuses, respiratory system, cervix, biliary tract, bladder, etc.
Class 3: accessible through skin without incision (laying shallow below the skin): thyroid, testicles; also shallow-laying lymph nodes, muscles and bones.
Class 4: accessible through minor incision: peritoneum, including pancreas, liver, ovaries, stomach, intestines, kidneys and spleen; also prostate, most blood vessels, glands, lymph nodes, muscles and bones.
Class 5: accessible through major incision or intraoperatively: brain and bone marrow.
Below, a selection of photopharmacological compounds reported is given. It aims at giving an overview on what has been done and is possible in the field of photopharmacology.
Class 1
Eyes/Vision Restoration
Target: Eye/Vision restoration
Molecular Target: AMPA receptor agonist
Inspired by: AMPA
Related Condition: Blindness
Active form: trans
Switching: 400-480 nm (cis)/thermal relaxation (trans)
Skin
Target: Skin
Molecular Target: Histone deacetylases (HDACs)
Inspired by: Vorinostat (SAHA)
Related Disease: Skin diseases: cutaneous T cell lymphoma/superficial spreading melanoma
Active form: cis
Switching: 365-400 nm (cis)/white light (trans)
Class 2
Target: Respiratory Tract
Molecular Target: Phosphoribosyl isomerase A (PriA)
Organism: Mycobacterium tuberculosis
Inspired by: ProFAR
Related Disease: tuberculosis
Active form: open
Switching: 312 nm (closed)/>420 nm (open)
Class 3
Target: Solid Tumors/Angiogenesis
Molecular Target: Tubulin (cholchicine-binding domain)
Inspired by: Combretastatin A4 (phosphate)
Related Disease: Cancer (e.g. Anaplastic Thyroid Carcinom)
Active form: cis
Switching: 390-430 nm (cis)/500-530 nm (trans)
Class 4
Target: Pancreas/β-cells/insulin secretion
Molecular Target: KATP channel–Epac2A signaling
Inspired by: Glimepiride
Related Disease: Type 2 diabetes mellitus
Active form: cis
Switching: 460 nm (cis)/thermal relaxation
Target: Pancreas/β-cells/insulin secretion
Molecular Target: KATP channel–Epac2A signaling
Inspired by: Glimepiride
Related Disease: Type 2 diabetes
Active form: cis
Switching: 520 nm (cis)/thermal relaxation
Target: Pancreass/Brain/insulin secretion
Molecular Target: Glucagon-like peptide-1 receptor (GLP-1R) signaling
Inspired by: GLP-1R agonist liraglutide
Related Disease: Type 2 diabetes
Active form:
- cis: increase of [cAMP]
- trans: increase of calcium influx
Switching: 330 - 370 nm (cis)/420 - 440 nm (trans)
Class 5
Bone Marrow
Target: Bone marrow
Molecular Target: Proteasome, blocks specific catalytic sites
Inspired by: Bortezomib (Velcade)
Related Disease: multiple myeloma/mantle cell lymphoma
Active form: cis
Switching: 365 nm (cis)/white light (trans)
Brain
Target: Brain
Molecular Target: acetylcholinesterase (AChE) blocker (PAS/CAS)
Inspired by: Tacrine (THA)
Related Disease: Alzheimer’s disease/ Aβ-plaque formation
Active form:
- Open: PAS (peripheral anionic site)
- Closed: CAS (catalytic active site)
Switching:
Target: Neuromuscular endplate
Molecular Target: acetylcholinesterase (AChE) blocker, cholinergic neurotransmission
Inspired by: Tacrine (THA)
Related Disease: Alzheimer’s disease
Active form: cis
Switching: 350 nm (cis)/440 nm (trans)
Target: sensory neuons
Molecular Target: transient receptor potential cation channel, member A1 (TrpA1)
Inspired by: None, behavior-based chemical screen
Related Disease: neuropathic pain/chronic inflammation
Activation: 405 nm
Non-Classified
Antibiotics
Molecular Target: DNA gyrase/blockage of DNA replication
Organism: Escherichia coli CS1562/Micrococcus luteus
Inspired by: Ciprofloxacin/Quinolone antibiotics
Related Disease: Bacterial Infections/Bacterial Resistance
Active form: cis
Switching: 365 nm (cis)/white light (trans)
Molecular Target: DNA gyrase/blockage of DNA replication
Organism:
- Azobenzene: Escherichia coli
- Spiropyran: Micrococcus luteus
Inspired by: Ciprofloxacin
Related Disease: Bacterial Infections
Active form:
- Azobenzene: cis
- Spiropyran: closed
Switching: 365 nm (cis)/530 nm (trans)
Molecular Target: Membrane disruption
Organism:
- Staphylococcus aureus
- Staphylococcus Epidermis
- Staphylococcus Xylosus
Inspired by: Gramicidin S
Related Disease: Bacterial Infections
Active form: open
Switching: 256 nm (closed)/530 nm (open)
Anesthetics
Target: Sensory system
Molecular Target: vanilloid receptor 1 (TrpV1) antagonist
Inspired by: capsazepin (CPZ)
Related Phenomenon: Nociception
Active form:
- cis: TrpV1 (CAP)
- trans: TrpV1 (voltage gated)
Switching: 360 nm (cis)/440 nm (trans)
Target: Sensory system
Molecular Target: vanilloid receptor 1 (TrpV1) antagonist
Inspired by: thio-BCTC
Related Phenomenon: Nociception
Active form: cis: TrpV1 (voltage gated)
Switching: 370 nm (cis)/470 nm (trans)
Target: Digestive tract/brain/spinal cord
Molecular Target: μ-opioid receptor (MOR) agonist
Inspired by: Fentanyl
Related Phenomenon: Nociception
Active form: trans
Switching: 340 - 360 nm (cis)/420 - 480 nm (trans)
Target: Intravenous general anesthetic
Molecular Target: Potentiator of γ-aminobutyric acid A (GABAA) receptors
Inspired by: Propofol
Related Phenomenon: Nociception
Active form: trans
Switching: 360–450 nm (cis)/thermal relaxation (trans)
Target: Brain/Cells
Molecular Target: Blocking Kv/Nav/voltage gated Ca2+ membrane channels
Inspired by: lidocaine/QX-314
Related Phenomenon: Nociception
Active form: trans
Switching: 380nm (cis)/500 nm (trans)
Target: Brain/Cells
Molecular Target: Blocking Shaker-IR/Kv/Nav membrane channels
Inspired by: lidocaine/QX-314
Related Phenomenon: Pain
Active form: trans
Switching: 420 nm (cis)
Target: Vanilloid Receptor 1 (TrpV1)
Molecular Target: TrpV1 agonist
Inspired by: Capsaicin
Related Phenomenon: Nociception
Active form: cis
Switching: 350-365 nm (cis)/450-460 nm (trans)
© 2017 Michael M. Lerch |