INT193281

Context Info Confidence 0.07 First Reported 2006 Last Reported 2008 Negated 0 Speculated 0 Reported most in Body Documents 7 Total Number 8 Disease Relevance 4.57 Pain Relevance 3.53

signal transduction (CAP1) cell morphogenesis (CAP1) plasma membrane (CAP1) cytoskeleton organization (CAP1) cytoplasm (CAP1)

Anatomy Link Frequency rim 1 aortic arch 1 edge 1 CAP1 (Homo sapiens)

Pain Link Frequency Relevance Heat qutenza 240 100.00 agonist 27 99.96 cva 408 99.36 Action potential 30 99.32 c fibre 48 86.64 Bioavailability 12 65.28 Potency 8 64.96 anticonvulsant 2 40.00 alcohol 3 22.48 cerebral cortex 12 5.00

Disease Link Frequency Relevance Heat Cv General 3 Under Development 399 99.36 Death 20 94.32 Liver Failure 2 89.08 Cancer 94 88.80 Pancytopenia 2 87.12 Toxicity 29 86.16 Tremor 2 83.72 Dizziness 4 83.24 Sleep Disorders 15 82.80 Apoptosis 26 65.68

Sentences Mentioned In

Key:

Protein

Mutation

Event

Anatomy

Negation

Speculation

Pain term

Disease term

CAP Index has an additional association with survival, good neurological outcome, and lack of need for interventions to lower ICP, independent of ICP and CPP.

CAP Binding (association) of associated with cva

1) Confidence 0.07 Published 2006 Journal Crit Care Section Body Doc Link PMC1794465 Disease Relevance 1.35 Pain Relevance 0.57

Good neurological outcome is independently associated with CAP Index (p = 0.0001), but not CPP (p = 0.29).

CAP Binding (associated) of

2) Confidence 0.07 Published 2006 Journal Crit Care Section Body Doc Link PMC1794465 Disease Relevance 1.13 Pain Relevance 0.50

Survival is independently associated with CAP Index and CPP (p = 0.0001).

CAP Binding (associated) of

3) Confidence 0.06 Published 2006 Journal Crit Care Section Body Doc Link PMC1794465 Disease Relevance 1.08 Pain Relevance 0.49

M concentration of CAP is close to the KD (2 ?

CAP Binding (concentration) of associated with qutenza

4) Confidence 0.05 Published 2006 Journal J Negat Results Biomed Section Body Doc Link PMC1481593 Disease Relevance 0 Pain Relevance 0.63

CAP was initially dissolved in DMSO and then mixed with PBS to a concentrated stock solution containing 300 ?

CAP Binding (dissolved) of associated with qutenza

5) Confidence 0.05 Published 2006 Journal J Negat Results Biomed Section Body Doc Link PMC1481593 Disease Relevance 0 Pain Relevance 0.49

M CAP, the BR was nearly inexcitable and only fired a scattering of action potentials to aortic arch pressures above its control threshold level (Figure 3).

CAP Binding (fired) of in aortic arch associated with action potential and qutenza

6) Confidence 0.05 Published 2006 Journal J Negat Results Biomed Section Body Doc Link PMC1481593 Disease Relevance 0 Pain Relevance 0.79

Despite the variety of their structural characteristics, HDAC inhibitors can be broadly characterized by a common “pharmacophore” model which consists in a surface domain (also named “CAP”), which is able to interact with the rim space at the entrance of the catalytic tunnel of the enzyme, linked to a hydrophobic spacer through a polar connection unit.

CAP Binding (interact) of in rim

7) Confidence 0.03 Published 2008 Journal Current Medicinal Chemistry Section Body Doc Link PMC2764862 Disease Relevance 0.19 Pain Relevance 0.03

According to the pharmacophore model, the hydroxamic group chelates the zinc atom at the active site of HDACs, while a hydrophobic cap and an aliphatic side chain respectively, interacts with the edge and fits into the hydrophobic catalytic pocket [89, 90].

cap Binding (interacts) of in edge

8) Confidence 0.02 Published 2008 Journal Current Medicinal Chemistry Section Body Doc Link PMC2764862 Disease Relevance 0.82 Pain Relevance 0.03

General Comments

This test has worked.