Compare the safety and efficacy of Tugain Eva (minoxidil 5 percent solution fortified with 0.0033 percent melatonin) with Tugain solution (minoxidil 5 percent solution) in female pattern hair loss - NIL

开始日期2024-10-15

申办/合作机构

Cipla Ltd.

CTRI/2024/09/073394 / Not yet recruiting临床1期IIT

Efficacy of autologous Growth Factor Concentrate injection and Platelet Rich Plasma injection in patients of Androgenic Alopecia receiving topical minoxidil: A randomized control trial - NIL

开始日期2024-09-22

申办/合作机构-

100 项与 ABCC9 x Kir6.2 相关的临床结果

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100 项与 ABCC9 x Kir6.2 相关的转化医学

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0 项与 ABCC9 x Kir6.2 相关的专利（医药）

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项与 ABCC9 x Kir6.2 相关的文献（医药）

2023-02-01·European Journal of Human Genetics

Lymphedema as first clinical presentation of Cantu Syndrome: reversed phenotyping after identification of gain-of-function variant in ABCC9

Article

作者: van Haaften, Gijs ; Alders, Marielle ; McClenaghan, Conor ; van Duinen, Kirsten ; Christiaans, Imke ; Nichols, Colin G ; Gao, Jian ; van Haelst, Mieke M

Cantu Syndrome (CS), [OMIM #239850] is characterized by hypertrichosis, osteochondrodysplasia, and cardiomegaly. CS is caused by gain-of-function (GOF) variants in the KCNJ8 or ABCC9 genes that encode pore-forming Kir6.1 and regulatory SUR2 subunits of ATP-sensitive potassium (K_ATP) channels. Many subjects with CS also present with the complication of lymphedema. A previously uncharacterized, heterozygous ABCC9 variant, p.(Leu1055_Glu1058delinsPro), termed indel1055, was identified in an individual diagnosed with idiopathic lymphedema. The variant was introduced into the equivalent position of rat SUR2A, and inside-out patches were used to characterize the K_ATP channels formed by Kir6.2 and WT or mutant SUR2A subunits coexpressed in Cosm6 cells. The indel1055 variant causes gain-of-function of the channel, with an increase of the IC₅₀ for ATP inhibition compared to WT. Retrospective consideration of this individual reveals clear features of Cantu Syndrome. An additional heterozygous ABCC9 variant, p.(Ile419Thr), was identified in a second individual diagnosed with lymphedema. In this case, there were no additional features consistent with CS, and the properties of p.(Ile416Thr) (the corresponding mutation in rat SUR2A)--containing channels were not different from WT. This proof-of-principle study shows that idiopathic lymphedema may actually be a first presentation of otherwise unrecognized Cantu Syndrome, but molecular phenotyping of identified variants is necessary to confirm relevance.

2023-01-02·Journal of General Physiology

A Cantú syndrome mutation produces dual effects on KATP channels by disrupting ankyrin B regulation

Article

作者: Cebrián, Jorge ; Tamargo, Juan ; Dago, María ; Delpón, Eva ; Rubio-Alarcón, Marcos ; Caballero, Ricardo ; Marín, María ; Cámara-Checa, Anabel ; Crespo-García, Teresa ; Nieto-Marín, Paloma ; Rapún, Josu

ATP-sensitive potassium (KATP) channels composed of Kir6.x and sulfonylurea receptor (SURs) subunits couple cellular metabolism to electrical activity. Cantú syndrome (CS) is a rare disease caused by mutations in the genes encoding Kir6.1 (KCNJ8) and SUR2A (ABCC9) that produce KATP channel hyperactivity due to a reduced channel block by physiological ATP concentrations. We functionally characterized the p.S1054Y SUR2A mutation identified in two CS carriers, who exhibited a mild phenotype although the mutation was predicted as highly pathogenic. We recorded macroscopic and single-channel currents in CHO and HEK-293 cells and measured the membrane expression of the channel subunits by biotinylation assays in HEK-293 cells. The mutation increased basal whole-cell current density and at the single-channel level, it augmented opening frequency, slope conductance, and open probability (Po), and promoted the appearance of multiple conductance levels. p.S1054Y also reduced Kir6.2 and SUR2A expression specifically at the membrane. Overexpression of ankyrin B (AnkB) prevented these gain- and loss-of-function effects, as well as the p.S1054Y-induced reduction of ATP inhibition of currents measured in inside-out macropatches. Yeast two-hybrid assays suggested that SUR2A WT and AnkB interact, while p.S1054Y interaction with AnkB is decreased. The p.E322K Kir6.2 mutation, which prevents AnkB binding to Kir6.2, produced similar biophysical alterations than p.S1054Y. Our results are the first demonstration of a CS mutation whose functional consequences involve the disruption of AnkB effects on KATP channels providing a novel mechanism by which CS mutations can reduce ATP block. Furthermore, they may help explain the mild phenotype associated with this mutation.

2023-01-01·Frontiers in pharmacology

Immunohistochemical, pharmacovigilance, and omics analyses reveal the involvement of ATP-sensitive K⁺ channel subunits in cancers: role in drug-disease interactions.

Article

作者: Zizzo, Nicola ; Tinelli, Antonella ; Antonacci, Marina ; Tricarico, Domenico ; Maqoud, Fatima ; Passantino, Giuseppe ; Ranieri, Girolamo ; Attimonelli, Marcella

ATP-sensitive-K⁺ channels (KATP) are involved in diseases, but their role in cancer is poorly described.Pituitary macroadenoma has been observed in Cantu' syndrome (C.S.), which is associated with the gain-of-function mutations of the ABCC9 and KCNJ8 genes.We tested the role of the ABCC8/Sur1, ABCC9/Sur2A/B, KCNJ11/Kir6.2, and KCNJ8/Kir6.1 genes exptl. in a minoxidil-induced renal tumor in male rats and in the female canine breast cancer, a spontaneous animal model of disease, and in the pharmacovigilance and omics databases.We performed biopsies from renal tissues of male rats (N = 5) following a sub-chronic high dosing topical administration of minoxidil (0.777-77.7 mg/kg/day) and from breast tissues of female dogs for diagnosis (N = 23) that were analyzed by immunohistochem.Pharmacovigilance and omics data were extracted from EudraVigilance and omics databases, resp.An elevated immunohistochem. reactivity to Sur2A-mAb was detected in the cytosol of the Ki67+/G3 cells other than in the surface membrane in the minoxidil-induced renal tumor and the breast tumor samples.KCNJ11, KCNJ8, and ABCC9 genes are upregulated in cancers but ABCC8 is downregulated.The Kir6.2-Sur2A/B-channel opener minoxidil showed 23 case reports of breast cancer and one case of ovarian cancer in line with omics data reporting, resp., and the neg. and pos. prognostic roles of the ABCC9 gene in these cancers.Sulfonylureas and glinides blocking the pancreatic Kir6.2-Sur1 subunits showed a higher risk for pancreatic cancer in line with the pos. prognostic role of the ABCC8 gene but low risks for common cancers.Glibenclamide, repaglinide, and glimepiride show a lower cancer risk within the KATP channel blockers.The Kir6.2-Sur1 opener diazoxide shows no cancer reactions.An elevated expression of the Sur2A subunit was found in proliferating cells in two animal models of cancer.Immunohistochem./omics/pharmacovigilance data reveal the role of the Kir6.1/2-Sur2A/B subunits as a drug target in breast/renal cancers and in C.S.