Congenital insensitivity to pain and anhydrosis due to a rare mutation and that is complicated by inflammatory bowel disease and amyloidosis: a case report

Bakri, Faris G.; Wahbeh, Ayman; Sneina, Awni Abu; Khader, Ali; Obeidat, Firas; AlAwwa, Izzat; Buni, Maryam; Ki, Chang‐Seok; Masri, Amira

doi:10.1002/ccr3.689

Cited by 4 publications

(4 citation statements)

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“…Activation of TrkA can lead to pathogenesis of many difficult to treat human pain conditions such as osteoarthritis and cancer-related types of pain. Loss-of-function TrkA variants are associated with congenital insensitivity to pain . Furthermore, in vivo TrkA inhibition studies indicate pain suppression effects , underlining the promise of TrkA as a pain target.…”

Section: Resultsmentioning

confidence: 99%

“…Loss-offunction TrkA variants are associated with congenital insensitivity to pain. 21 Furthermore, in vivo TrkA inhibition studies indicate pain suppression effects 22,23 underlining the promise of TrkA as a pain target. Other selective pan-Trk inhibitors already exist 24−27 and show promise for the treatment of acute and chronic pain.…”

Section: ■ Results and Discussionmentioning

confidence: 99%

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From Cancer to Pain Target by Automated Selectivity Inversion of a Clinical Candidate

2018

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Elimination of inadvertent binding is crucial for inhibitor design targeting conserved protein classes like kinases. Compounds in clinical trials provide a rich source for initiating drug design efforts by exploiting such secondary binding events. Considering both aspects, we shifted the selectivity of tozasertib, originally developed against AurA as cancer target, toward the pain target TrkA. First, selectivity-determining features in binding pockets were identified by fusing interaction grids of several key and off-target conformations. A focused library was subsequently created and prioritized using a multiobjective selection scheme that filters for selective and highly active compounds based on orthogonal methods grounded in computational chemistry and machine learning. Eighteen high-ranking compounds were synthesized and experimentally tested. The top-ranked compound has 10000-fold improved selectivity versus AurA, nanomolar cellular activity, and is highly selective in a kinase panel. This was achieved in a single round of automated in silico optimization, highlighting the power of recent advances in computer-aided drug design to automate design and selection processes.

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Section: Resultsmentioning

confidence: 99%

Section: ■ Results and Discussionmentioning

confidence: 99%

From Cancer to Pain Target by Automated Selectivity Inversion of a Clinical Candidate

2018

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“…CIPA merupakan penyakit autosomal resesif langka yang ditandai dengan hiperpireksia, anhidrosis, insensitivitas terhadap nyeri dan self-mutilation serta beberapa kasus terkait dengan retardasi mental. Penyakit Ini diklasifikasikan dalam kelompok penyakit Hereditary Sensory and Autonomic Neuropathies (HSAN) IV (Bakri et al 2016).…”

Section: Hasil Dan Pembahasanunclassified

“…CIPA adalah penyakit autosomal resesif HSAN IV yang memiliki gejala klasik insensitivitas nyeri, anhidrosis dan retardasi mental serta gejala lain yang mungkin saja muncul pada sistem saraf sensorik dan otonom, kognitif, gastrointestinal, respiratori, kardiovaskular dan muskuloskeletal. CIPA terjadi akibat mutasi NTRK1 yang menyebabkan perubahan pada TrkA, reseptor NGF (pengatur neuron sensorik nosiseptif dan neuron otonom simpatik) (Bakri et al 2016;Nabyev et al 2018;Pérez-López, et all. 2015).…”

Section: Kesimpulanunclassified

Congenital insensitivity to pain with anhidrosis (CIPA): sebuah artikel dan manajemen anestesi

Sugihen

2022

SEHATI

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Congenital insensitivity to pain with anhidrosis (CIPA) is hereditary sensory and autonomic neuropathies (HSAN) type IV caused by mutations in NTRK1 gene (neurotrophic tyrosine kinase receptor 1) located in chromosome 1q21-22, encoding the tyrosinase domain receptor high affinity nerve growth factor. It is characterized by anhidrosis, insensitivity to painful stimuli and mental retardation. Given their low prevalence from few reported cases, it is important to know its sign and symptomp to be considered in the differential diagnosis. Therapy for CIPA remains unclear. Complication prevention is the only possible treatment of CIPA. In anesthetic management during surgery, those patients should still administred by analgesics for sedation and anxiolytic effects.

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Congenital insensitivity to pain with anhidrosis syndrome: A series from Jordan

Masri

Shboul

Khasawneh

et al. 2020

Clinical Neurology and Neurosurgery

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Congenital insensitivity to pain and anhydrosis due to a rare mutation and that is complicated by inflammatory bowel disease and amyloidosis: a case report

Abstract: Key Clinical MessagePatients with congenital insensitivity to pain and anhydrosis syndrome are at risk for renal amyloidosis and inflammatory bowel disease. Physicians caring for such patients should be aware of these complications.

Cited by 4 publications

References 23 publications

From Cancer to Pain Target by Automated Selectivity Inversion of a Clinical Candidate

From Cancer to Pain Target by Automated Selectivity Inversion of a Clinical Candidate

Congenital insensitivity to pain with anhidrosis (CIPA): sebuah artikel dan manajemen anestesi

Congenital insensitivity to pain with anhidrosis syndrome: A series from Jordan

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