Classification of targets

 

The proposed classification follows: Angew. Chem. Int. Ed. 2016, 55, 1097810999

 

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.

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)

     

    ACS Chem. Neurosci. 2016, 7, 15–20

    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)

     

    Chem. Eur. J. 2015, 21, 16517 – 16524

  • 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)

     

    Angew. Chem. Int. Ed. 2014, 53, 595–598

  • 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)

     

    Cell 2015, 162, 403 – 411

    Org. Lett. 2015, 17, 4546 – 4549

    Org. Biomol. Chem. 2016, 14, 40 – 49

  • 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

     

    Nat. Commun. 2014, 5, 5116

    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

     

    Chem. Commun. 2015, 51, 6018 – 6021

    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)

     

    Angew. Chem. Int. Ed. 2015, 54, 15565 – 15569

  • 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)

     

    ChemBioChem 2014, 15, 2053–2057

    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:

     

    ACS Chem. Neurosci. 2014, 5, 377–389

    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)

     

    Angew. Chem. Int. Ed. 2014, 53, 7657–7660

    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

     

    Nat. Chem. Biol. 2013, 9, 257–263

  • 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)

     

    Nat. Chem. 2013, 5, 924–928

    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)

     

    Bioconjugate Chem. 2015, 26, 2592–2597

    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)

     

    Angew. Chem. Int. Ed. 2014, 53, 3392–3395

    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)

     

    Angew. Chem. Int. Ed. 2013, 52, 9845–9848

    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)

     

    Angew. Chem. Int. Ed. 2013, 52, 9845–9848

    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)

     

    Angew. Chem. Int. Ed. 2014, 53, 3264-3267

    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)

     

    Angew. Chem. Int. Ed. 2012, 51, 10500-10504

    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)

     

    Nat. Methods 2012, 9, 396–402

    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)

     

    ChemBioChem 2012, 13, 1746–1749

    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)

     

    Nat. Commun. 2015, 6, 7118

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Background: subtle patterns