PF-05089771 / Pfizer 
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 13 Diseases   1 Trial   1 Trial   64 News 
  • ||||||||||  Tectin (tetrodotoxin) / CK Life Sci, PF-05089771 / Pfizer
    Journal:  Role of NaV1.7 in postganglionic sympathetic nerve function in human and guinea-pig arteries. (Pubmed Central) -  May 15, 2024   
    Electrical field stimulation (EFS) induced rapid contractions in guinea-pig isolated aorta, pulmonary arteries, and human isolated pulmonary arteries via stimulation of intrinsic nerves, which were inhibited by prazosin or the NaV1 blocker tetrodotoxin...NaV1.7 blockade substantially inhibits sympathetic nerve-mediated adrenergic contractions in human and guinea-pig blood vessels. Pharmacologically blocking NaV1.7 profoundly affects sympathetic and parasympathetic responses in addition to sensory fibres, prompting exploration into the broader physiological consequences of NaV1.7 mutations on autonomic nerve activity.
  • ||||||||||  PF-05089771 / Pfizer
    Preclinical, Journal:  Influence of combined voltage-gated sodium channel Na1.7 and Na1.8 inhibitors on cough in a guinea pig model. (Pubmed Central) -  Apr 11, 2023   
    In this study, we demonstrated that inhaled aerosol of Na1.7 inhibitor PF-05089771 (10?M) and Na1.8 inhibitor A-803467 (1mM) mixture inhibited the capsaicin-induced cough by ?60% and citric acid-induced cough by ?65% at doses that did not modify respiratory rate. Our previous and present studies indicate that Na1.7 and Na1.8 may present promising therapeutic targets for antitussive therapy.
  • ||||||||||  PF-05089771 / Pfizer
    Preclinical, Journal:  Ectopic expression of Nav1.7 in spinal dorsal horn neurons induced by NGF contributes to neuropathic pain in a mouse spinal cord injury model. (Pubmed Central) -  Mar 21, 2023   
    Pharmacologic studies demonstrated that the efficacy of the blood-brain-barrier (BBB) permeable Nav1.7 inhibitor GNE-0439 for attenuation of NP in SCI mice was significantly better than that of the BBB non-permeable Nav1.7 inhibitor PF-05089771...In conclusion, our findings showed that the upregulation of Nav1.7 was induced by SCI in both SDH and DRG neurons through increased expression of NGF/JUN, and the inhibition of Nav1.7 in both peripheral and spinal neurons alleviated mechanical pain in SCI mice. These data suggest that BBB permeable Nav1.7 blockers might relieve NP in patients with SCI and that blocking the upregulation of Nav1.7 in the early stage of SCI via selective inhibition of the downstream signaling pathways of NGF or Nav1.7-targeted RNA drugs could be a strategy for therapy of SCI-induced NP.
  • ||||||||||  PF-05089771 / Pfizer
    Preclinical, Journal:  Long-Term Blockade of Nociceptive Na1.7 Channels Is Analgesic in Rat Models of Knee Arthritis. (Pubmed Central) -  Nov 16, 2022   
    This study examined the effect of Na1.7 blockade on joint pain using either the small molecule inhibitor PF05089771 or an antibody directed towards the intracellular domain of the ion channel...These data indicate that joint pain associated with neural demyelination can be alleviated somewhat by Na1.7 channel blockade. Biologics that inactivate Na1.7 channels have the potential to reduce arthritis pain over a protracted period of time.
  • ||||||||||  Tectin (tetrodotoxin) / WEX Pharma, PF-05089771 / Pfizer
    Preclinical, Journal:  Functional expression of Na1.7 channels in freshly dispersed mouse bronchial smooth muscle cells. (Pubmed Central) -  Sep 10, 2022   
    These effects were readily reversed to control-like activity by tetrodotoxin (100 nM). In conclusion, mouse bronchial SMC functionally express Na1.7 channels that are capable of modulating contractile activity, at least under experimental conditions.
  • ||||||||||  PF-05089771 / Pfizer
    Journal:  The effect of the voltage-gated sodium channel Na1.7 blocker PF-05089771 on cough in the guinea pig. (Pubmed Central) -  Apr 19, 2022   
    Compared to vehicle, peroral or inhaled PF-05089771 administration caused about 50-60% inhibition of cough at the doses that did not alter respiratory rate. We conclude that the Na1.7 blocker PF-05089771 inhibits cough in a manner consistent with its electrophysiological effect on airway C-fibre nerve terminals.
  • ||||||||||  Tectin (tetrodotoxin) / WEX Pharma, ICA-1 / University of South Florida, PF-05089771 / Pfizer
    Journal:  Role of NaV1.7 in Action Potential Conduction along Human Bronchial Vagal Afferent C-fibers. (Pubmed Central) -  Apr 14, 2022   
    NaV1.7 blockers can prevent action potential conduction in the majority of vagal C-fibers arising from human bronchi. Blockers of NaV1.7 channels may therefore have value in inhibiting the responses to excessive airway C-fiber activation in inflammatory airway disease; responses that include coughing as well as reflex bronchoconstriction and secretions.
  • ||||||||||  Review, Journal:  Peripheral Voltage-Gated Cation Channels in Neuropathic Pain and Their Potential as Therapeutic Targets. (Pubmed Central) -  Mar 18, 2022   
    Despite this, peripheral voltage-gated cation channels retain their promise as therapeutic targets. The way forward may include (i) further structural refinement of K channel activators such as retigabine and ASP0819 to improve selectivity and limit toxicity; use or modification of Na channel blockers such as vixotrigine, PF-05089771, A803467, PF-01247324, VX-150 or arachnid toxins such as Tap1a; the use of Ca channel blockers such as TTA-P2, TTA-A2, Z 944, ACT709478, and CNCB-2; (ii) improving methods for assessing "pain" as opposed to nociception in rodent models; (iii) recognizing sex differences in pain etiology; (iv) tailoring of therapeutic approaches to meet the symptoms and etiology of pain in individual patients via quantitative sensory testing and other personalized medicine approaches; (v) targeting genetic and biochemical mechanisms controlling channel expression using anti-NGF antibodies such as tanezumab or re-purposed drugs such as vorinostat, a histone methyltransferase inhibitor used in the management of T-cell lymphoma, or cercosporamide a MNK 1/2 inhibitor used in treatment of rheumatoid arthritis; (vi) combination therapy using drugs that are selective for different channel types or regulatory processes; (vii) directing preclinical validation work toward the use of human or human-derived tissue samples; and (viii) application of molecular biological approaches such as clustered regularly interspaced short palindromic repeats (CRISPR) technology.
  • ||||||||||  Tectin (tetrodotoxin) / WEX Pharma, PF-05089771 / Pfizer
    Preclinical, Journal:  Histamine Sensitization of the Voltage-Gated Sodium Channel Nav1.7 Contributes to Histaminergic Itch in Mice. (Pubmed Central) -  Mar 5, 2022   
    Importantly, selective inhibition of Nav1.7 by PF-05089771 significantly relieved the scratching frequency in a histamine-dependent itch model induced by compound 48/80. Taken together, these data suggest that activation of H1 receptors by histamine sensitizes Nav1.7 channels through the PKC pathway in DRG neurons that contributes to histamine-dependent itch.
  • ||||||||||  Tectin (tetrodotoxin) / WEX Pharma, PF-05089771 / Pfizer
    Journal:  Voltage-gated sodium channels mediating conduction in vagal motor fibers innervating the esophageal striated muscle. (Pubmed Central) -  Oct 22, 2021   
    The selective NaV1.7 inhibitor PF-05089771 alone partially inhibited contractions and caused a >3-fold rightward shift in the TTX concentration-inhibition curve...We conclude that the action potential conduction in the vagal motor fibers to the esophageal striated muscle in the mouse is mediated by TTX-sensitive voltage gated sodium channels including NaV1.7 and most probably NaV1.6. The role of NaV1.6 is supported by ruling out other TTX-sensitive NaV1s (NaV1.1-1.4) in the NaV1.7-independent conduction.
  • ||||||||||  PF-05089771 / Pfizer
    Journal:  Sensory neuron-derived Na1.7 contributes to dorsal horn neuron excitability. (Pubmed Central) -  Oct 27, 2020   
    Na1.7 blocker PF05089771 diminished excitability in dorsal horn neurons but had no effect on Na1.7 null mutant mice. These data demonstrate an unsuspected functional role of primary afferent neuron-generated Na1.7 in dorsal horn neurons and an expression pattern that would not be predicted by transcriptomic analysis.
  • ||||||||||  PF-05089771 / Pfizer
    Journal:  Lidocaine binding enhances inhibition of Nav1.7 channels by the sulfonamide PF-05089771. (Pubmed Central) -  Aug 4, 2020   
    The gating state-mediated interaction between the compounds illustrates a principle applicable to many state-dependent agents. SIGNIFICANCE STATEMENT: The results show that lidocaine enhances the degree and rate of inhibition of Nav1.7 channels by the aryl sulfonamide compound PF-05089771, consistent with state-dependent binding by lidocaine increasing the fraction of channels presenting a high-affinity binding site for PF-05089771 and suggesting that combinations of agents targeted to the pore-region binding site of lidocaine and the external binding site of aryl sulfonamides may have synergistic actions.
  • ||||||||||  PF-05089771 / Pfizer
    Biomarker, Journal:  The voltage-gated sodium channel Na1.7 associated with endometrial cancer. (Pubmed Central) -  Oct 11, 2019   
    Inhibition of this channel by Na1.7 blocker PF-05089771, promoted cancer apoptosis and attenuated cancer cell invasion. These results establish a relationship between voltage-gated sodium channel protein and endometrial cancer, and suggest that Na1.7 is a potential prognostic biomarker and could serve as a novel therapeutic target for endometrial cancer.
  • ||||||||||  PF-05089771 / Pfizer
    Trial completion:  Drug-Drug Interaction Study With PF-05089771 (clinicaltrials.gov) -  Jan 14, 2014   
    P1,  N=17, Completed, 
    Not yet recruiting --> Recruiting Recruiting --> Completed