1589527-65-0
1589527-65-0 structure
- Name: KIRA6
- Chemical Name: KIRA6
- CAS Number: 1589527-65-0
- Molecular Formula: C28H25F3N6O
- Molecular Weight: 518.533
- Catalog: Signaling Pathways Cell Cycle/DNA Damage IRE1
- Create Date: 2018-05-19 08:21:34
- Modify Date: 2024-01-14 01:12:22
-
KIRA6 allosterically inhibits IRE1α RNase kinase activity with an IC50 of 0.6 µM.
| Name | KIRA6 |
|---|---|
| Synonyms |
1-{4-[8-Amino-3-(2-methyl-2-propanyl)imidazo[1,5-a]pyrazin-1-yl]-1-naphthyl}-3-[3-(trifluoromethyl)phenyl]urea
Urea, N-[4-[8-amino-3-(1,1-dimethylethyl)imidazo[1,5-a]pyrazin-1-yl]-1-naphthalenyl]-N'-[3-(trifluoromethyl)phenyl]- |
| Description | KIRA6 allosterically inhibits IRE1α RNase kinase activity with an IC50 of 0.6 µM. |
|---|---|
| Related Catalog | |
| Target |
IC50: 0.6 µM (IRE1α RNase kinase)[1] |
| In Vitro | KIRA6 dose-dependently inhibits IRE1α (WT) kinase activity, XBP1 RNA cleavage, Ins2 RNA cleavage and oligomerization. KIRA6 strongly inhibits JNK phosphorylation from IRE1α hyperactivation or ER stress. Also, KIRA6 dose-dependently inhibits Ins1 mRNA decay, proinsulin depletion, and apoptosis from IRE1α hyperactivation. In INS-1 cells, KIRA6 inhibits IRE1α auto-phosphorylation by Tg and XBP1 mRNA splicing by Tm in a dose-dependent manner. KIRA6 reduces ER stress-induced death of cultured cells and in pancreatic islet explants[1]. |
| In Vivo | KIRA6 has negligible toxicity up to 10 μM, providing a favorable therapeutic index to test cytoprotection. KIRA6 in BALB/c mice intraperitoneally (i.p.) dosed at 10 mg/kg shows good drug plasma AUC levels with moderate clearance (22.4 mL/min/kg). Drug half-life is 3.90 hours, Cmax is 3.3 μM, and plasma levels at 4 and 8hr are 1.2 μM and 0.33 μM, respectively. Intravitreal co-injection of KIRA6 with Tm significantly reduces XBP1 splicing, TXNIP induction, and decay of the ER-localized photoreceptor-specific Rhodopsin mRNA. KIRA6 dose-dependently inhibits Rhodopsin RNA cleavage by IRE1α. Concomitant with blockage of Terminal UPR outputs, co-injection of KIRA6 in the Tm model reduces photoreceptor loss by Optical Coherence Tomography (OCT) and histology. KIRA6 substantially protects against loss of ERG responsiveness, significantly preserving both a- and b-wave amplitudes[1]. |
| Animal Admin | Mice: Male Ins2+/Akita mice are injected i.p. with KIRA6 in a 2 mg/mL. Same solution without KIRA6 is denoted as Vehicle. C567BL/6 mice are also injected with same KIRA6 solution and indicated doses of Tm for liver analysis[1]. |
| References |
| Density | 1.4±0.1 g/cm3 |
|---|---|
| Molecular Formula | C28H25F3N6O |
| Molecular Weight | 518.533 |
| Exact Mass | 518.204224 |
| LogP | 6.26 |
| Index of Refraction | 1.645 |
| Storage condition | -20℃ |