A Child with Non-Growth Hormone-Deficient Short Stature with Chromosome 2 Deletion of 2q35-36.1: A Case Report and Literature Review of Haploinsufficiency of Epha4 Gene DOI
Jun Sun,

Ya Xiao,

Shuqin Jiang

et al.

Journal of Pediatric Genetics, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 4, 2024

Abstract Non-growth hormone-deficient short stature is a group of growth developmental disorders with complex pathophysiological mechanisms involving multiple pathways, including abnormalities in the hormone/insulin-like factor 1 signal pathway. We report 4-year-old girl severe and delay: her height was 91 cm (<–3 standard deviation [SD]), rate 3 to 4 cm/year (<–2 SD). Growth hormone stimulation tests indicated normal peak level (11.1 μg/L), while insulin-like factor-1 levels were reduced (7.98 nmol/L, <–1SD). Whole exome sequencing copy number variation analysis revealed 3.19 Mb deletion at 2q35-q36.1 on chromosome 2, encompassing all coding regions Epha4 gene. This study suggests an association between gene non-growth stature, highlighting importance further research this its related signaling pathways understand molecular disease potential therapeutic approaches.

Language: Английский

Back-Pocket Optimization of 2-Aminopyrimidine-Based Macrocycles Leads to Potent EPHA2/GAK Kinase Inhibitors DOI

Joshua Gerninghaus,

Rezart Zhubi, Andreas Krämer

et al.

Journal of Medicinal Chemistry, Journal Year: 2024, Volume and Issue: 67(15), P. 12534 - 12552

Published: July 19, 2024

Macrocyclization of acyclic compounds is a powerful strategy for improving inhibitor potency and selectivity. Here we have optimized 2-aminopyrimidine-based macrocycles to use these as chemical tools the ephrin kinase family. Starting with promiscuous macrocyclic inhibitor,

Language: Английский

Citations

5
Lipidation and PEGylation strategies to prolong the in vivo half-life of a nanomolar EphA4 receptor antagonist DOI
Maricel Gómez‐Soler,

Erika Olson,

Elena Rubio de la Torre

et al.

European Journal of Medicinal Chemistry, Journal Year: 2023, Volume and Issue: 262, P. 115876 - 115876

Published: Oct. 16, 2023

Language: Английский

Citations

3
Back-pocket optimization of 2-aminopyrimidine-based macrocycles leads to potent dual EPHA2/GAK kinase inhibitors with antiviral activity DOI Creative Commons

Joshua Gerninghaus,

Rezart Zhubi,

Andreas Kraemer

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Feb. 18, 2024

Macrocyclization of acyclic compounds is a powerful strategy for improving inhibitor potency and selectivity. Here, we developed 2-aminopyrimidine-based macrocyclic dual EPHA2/GAK kinase as chemical tool to study the role these two kinases in viral entry assembly. Starting with promiscuous inhibitor, 6, performed structure-guided activity relationship selectivity using panel over 100 kinases. The crystal structure EPHA2 complex macrocycle 23 provided basis further optimization by specifically targeting back pocket, resulting compound 55 potent inhibitor. Subsequent front-pocket derivatization resulted an interesting cellulo profile, favoring EPHA4 other ephrin receptor family members. prevented dengue virus infection Huh7 liver cells, mainly via its activity, therefore promising candidate against virus.

Language: Английский

Citations

0
Evaluation of NUN-004, a Novel Engineered Ephrin Antagonist, in Healthy Volunteers and Patients with Amyotrophic Lateral Sclerosis: A Phase I/Ib, Open-Label, Escalating Dose and Extended Access Study DOI

Michael Gerometta,

Robert D. Henderson,

Richard Friend

et al.

Clinical Drug Investigation, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 2, 2024

Language: Английский

Citations

0
A Child with Non-Growth Hormone-Deficient Short Stature with Chromosome 2 Deletion of 2q35-36.1: A Case Report and Literature Review of Haploinsufficiency of Epha4 Gene DOI
Jun Sun,

Ya Xiao,

Shuqin Jiang

et al.

Journal of Pediatric Genetics, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 4, 2024

Abstract Non-growth hormone-deficient short stature is a group of growth developmental disorders with complex pathophysiological mechanisms involving multiple pathways, including abnormalities in the hormone/insulin-like factor 1 signal pathway. We report 4-year-old girl severe and delay: her height was 91 cm (<–3 standard deviation [SD]), rate 3 to 4 cm/year (<–2 SD). Growth hormone stimulation tests indicated normal peak level (11.1 μg/L), while insulin-like factor-1 levels were reduced (7.98 nmol/L, <–1SD). Whole exome sequencing copy number variation analysis revealed 3.19 Mb deletion at 2q35-q36.1 on chromosome 2, encompassing all coding regions Epha4 gene. This study suggests an association between gene non-growth stature, highlighting importance further research this its related signaling pathways understand molecular disease potential therapeutic approaches.

Language: Английский

Citations

0