Synonym
KIRA8; KIRA 8; KIRA-8; AMG-18; AMG18; AMG 18; Amgen IRE1α Inhibitor
IUPAC/Chemical Name
(S)-2-Chloro-N-(6-methyl-5-((3-(2-(piperidin-3-ylamino)pyrimidin-4-yl)pyridin-2-yl)oxy)naphthalen-1-yl)benzenesulfonamide
InChi Key
XMWUCMFVDXDRDE-NRFANRHFSA-N
InChi Code
InChI=1S/C31H29ClN6O3S/c1-20-13-14-22-23(8-4-11-27(22)38-42(39,40)28-12-3-2-10-25(28)32)29(20)41-30-24(9-6-17-34-30)26-15-18-35-31(37-26)36-21-7-5-16-33-19-21/h2-4,6,8-15,17-18,21,33,38H,5,7,16,19H2,1H3,(H,35,36,37)/t21-/m0/s1
SMILES Code
O=S(C1=CC=CC=C1Cl)(NC2=C3C=CC(C)=C(OC4=NC=CC=C4C5=NC(N[C@@H]6CNCCC6)=NC=C5)C3=CC=C2)=O
Purity
>98% (or refer to the Certificate of Analysis)
Shipping Condition
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility
Soluble in DMSO
Shelf Life
>3 years if stored properly
Drug Formulation
This drug may be formulated in DMSO
Stock Solution Storage
0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code
2934.99.9001
Biological target:
Kira8 (AMG-18) is a mono-selective IRE1α inhibitor that allosterically attenuates IRE1α RNase activity with an IC50 of 5.9 nM.
In vitro activity:
Finally, KIRA8 treatment increases the differentiation of Krt19CreERT2-lineage-traced DATPs into type 1 alveolar epithelial cells after bleomycin injury, indicating that relief from IRE1α signaling enables DATPs to exit the transitional state.
Reference: Am J Physiol Lung Cell Mol Physiol. 2022 Apr 1;322(4):L564-L580. https://pubmed.ncbi.nlm.nih.gov/35170357/
In vivo activity:
Significantly, a specific IRE1α kinase-inhibiting RNase attenuator, KIRA8, attenuated NASH (non-alcoholic steatohepatitis) in mice.
Reference: Biochem Biophys Res Commun. 2022 Dec 3;632:158-164. https://pubmed.ncbi.nlm.nih.gov/36209584/
|
Solvent |
mg/mL |
mM |
| Solubility |
| Water |
30.0 |
49.91 |
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.
Preparing Stock Solutions
The following data is based on the
product
molecular weight
601.12
Batch specific molecular weights may vary
from batch to batch
due to the degree of hydration, which will
affect the solvent
volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass |
1 mg |
5 mg |
10 mg |
| 1 mM |
1.15 mL |
5.76 mL |
11.51 mL |
| 5 mM |
0.23 mL |
1.15 mL |
2.3 mL |
| 10 mM |
0.12 mL |
0.58 mL |
1.15 mL |
| 50 mM |
0.02 mL |
0.12 mL |
0.23 mL |
Formulation protocol:
1. Auyeung VC, Downey MS, Thamsen M, Wenger TA, Backes BJ, Sheppard D, Papa FR. IRE1α drives lung epithelial progenitor dysfunction to establish a niche for pulmonary fibrosis. Am J Physiol Lung Cell Mol Physiol. 2022 Apr 1;322(4):L564-L580. doi: 10.1152/ajplung.00408.2021. Epub 2022 Feb 16. PMID: 35170357; PMCID: PMC8957349.
2. Zhao S, Liu X, Li L, Kong X, Sun W, Loomes K, Nie T, Hui X, Wu D. KIRA8 attenuates non-alcoholic steatohepatitis through inhibition of the IRE1α/XBP1 signalling pathway. Biochem Biophys Res Commun. 2022 Dec 3;632:158-164. doi: 10.1016/j.bbrc.2022.09.098. Epub 2022 Sep 29. PMID: 36209584.
3. Thamsen M, Ghosh R, Auyeung VC, Brumwell A, Chapman HA, Backes BJ, Perara G, Maly DJ, Sheppard D, Papa FR. Small molecule inhibition of IRE1α kinase/RNase has anti-fibrotic effects in the lung. PLoS One. 2019 Jan 9;14(1):e0209824. doi: 10.1371/journal.pone.0209824. PMID: 30625178; PMCID: PMC6326459.
In vitro protocol:
1. Auyeung VC, Downey MS, Thamsen M, Wenger TA, Backes BJ, Sheppard D, Papa FR. IRE1α drives lung epithelial progenitor dysfunction to establish a niche for pulmonary fibrosis. Am J Physiol Lung Cell Mol Physiol. 2022 Apr 1;322(4):L564-L580. doi: 10.1152/ajplung.00408.2021. Epub 2022 Feb 16. PMID: 35170357; PMCID: PMC8957349.
In vivo protocol:
1. Zhao S, Liu X, Li L, Kong X, Sun W, Loomes K, Nie T, Hui X, Wu D. KIRA8 attenuates non-alcoholic steatohepatitis through inhibition of the IRE1α/XBP1 signalling pathway. Biochem Biophys Res Commun. 2022 Dec 3;632:158-164. doi: 10.1016/j.bbrc.2022.09.098. Epub 2022 Sep 29. PMID: 36209584.
2. Thamsen M, Ghosh R, Auyeung VC, Brumwell A, Chapman HA, Backes BJ, Perara G, Maly DJ, Sheppard D, Papa FR. Small molecule inhibition of IRE1α kinase/RNase has anti-fibrotic effects in the lung. PLoS One. 2019 Jan 9;14(1):e0209824. doi: 10.1371/journal.pone.0209824. PMID: 30625178; PMCID: PMC6326459.
1: Thamsen M, Ghosh R, Auyeung VC, Brumwell A, Chapman HA, Backes BJ, Perara G, Maly DJ, Sheppard D, Papa FR. Small molecule inhibition of IRE1α kinase/RNase has anti-fibrotic effects in the lung. PLoS One. 2019 Jan 9;14(1):e0209824. doi: 10.1371/journal.pone.0209824. eCollection 2019. PubMed PMID: 30625178; PubMed Central PMCID: PMC6326459.
2: Morita S, Villalta SA, Feldman HC, Register AC, Rosenthal W, Hoffmann-Petersen IT, Mehdizadeh M, Ghosh R, Wang L, Colon-Negron K, Meza-Acevedo R, Backes BJ, Maly DJ, Bluestone JA, Papa FR. Targeting ABL-IRE1α Signaling Spares ER-Stressed Pancreatic β Cells to Reverse Autoimmune Diabetes. Cell Metab. 2017 Apr 4;25(4):883-897.e8. doi: 10.1016/j.cmet.2017.03.018. Erratum in: Cell Metab. 2017 May 2;25(5):1207. PubMed PMID: 28380378; PubMed Central PMCID: PMC5497784.
