Synonym
SRI-37330 hydrochloride; SRI37330 hydrochloride; SRI 37330 hydrochloride; SRI-37330 HCl; SRI37330 HCl; SRI 37330 HCl;
IUPAC/Chemical Name
N-((1-(6-(trifluoromethyl)quinazolin-4-yl)piperidin-3-yl)methyl)methanesulfonamide hydrochloride
InChi Key
SIWGSSRKYJTJTF-UHFFFAOYSA-N
InChi Code
InChI=1S/C16H19F3N4O2S.ClH/c1-26(24,25)22-8-11-3-2-6-23(9-11)15-13-7-12(16(17,18)19)4-5-14(13)20-10-21-15;/h4-5,7,10-11,22H,2-3,6,8-9H2,1H3;1H
SMILES Code
CS(=O)(NCC1CN(C2=C3C=C(C(F)(F)F)C=CC3=NC=N2)CCC1)=O.[H]Cl
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
>2 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
More Info
Diabetes is characterized by hyperglycemia, loss of functional islet beta cell mass, deficiency of glucose-lowering insulin, and persistent alpha cell secretion of gluconeogenic glucagon. Still, no therapies that target these underlying processes are available
Biological target:
SRI-37330 hydrochloride is an orally bioavailable thioredoxin-interacting protein (TXNIP) inhibitor.
In vitro activity:
Transient transfection experiments showed that SRI-37330 inhibited the activity of the human TXNIP promoter in INS-1 cells by
~70% (Fig. 1b), consistent with inhibition at the transcriptional level. SRI-37330 also inhibited endogenous TXNIP mRNA expression
as shown by 7-point dose-response qRT-PCR assays (Fig. 1c), revealing an IC50 of 0.64 μM and no cytotoxicity (Supplemental Table
S1a). Similarly, SRI-37330 also inhibited TXNIP protein levels in a dose-dependent manner (Fig. 1d).
Reference: Cell Metab. 2020 Sep 1;32(3):353-365.e8. https://pubmed.ncbi.nlm.nih.gov/32726606/
In vivo activity:
Intraperitoneal glucose tolerance tests (GTTs) revealed a consistently and significantly improved glucose tolerance in response to SRI37330 administration (Fig. 3c), whereas insulin tolerance tests (ITTs) remained unaltered (Fig. 3d). Fasting blood glucose was
slightly, but significantly lower in SRI-37330-treated mice (Fig. 3e). Notably, while fasting serum insulin levels were unchanged in
SRI-37330-treated mice as compared to controls (Fig. 3f), fasting serum glucagon levels were lower (Fig. 3g), suggesting that SRI37330 may also affect glucagon secretion from pancreatic alpha cells.
Reference: Cell Metab. 2020 Sep 1;32(3):353-365.e8. https://pubmed.ncbi.nlm.nih.gov/32726606/
|
Solvent |
mg/mL |
mM |
comments |
| Solubility |
| DMSO |
62.5 |
147.10 |
|
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
424.87
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. Thielen LA, Chen J, Jing G, Moukha-Chafiq O, Xu G, Jo S, Grayson TB, Lu B, Li P, Augelli-Szafran CE, Suto MJ, Kanke M,
Sethupathy P, Kim JK, Shalev A. Identification of an Anti-diabetic, Orally Available Small Molecule that Regulates TXNIP
Expression and Glucagon Action. Cell Metab. 2020 Sep 1;32(3):353-365.e8. doi: 10.1016/j.cmet.2020.07.002. Epub 2020 Jul 28.
PMID: 32726606; PMCID: PMC7501995.
In vitro protocol:
1. Thielen LA, Chen J, Jing G, Moukha-Chafiq O, Xu G, Jo S, Grayson TB, Lu B, Li P, Augelli-Szafran CE, Suto MJ, Kanke M,
Sethupathy P, Kim JK, Shalev A. Identification of an Anti-diabetic, Orally Available Small Molecule that Regulates TXNIP
Expression and Glucagon Action. Cell Metab. 2020 Sep 1;32(3):353-365.e8. doi: 10.1016/j.cmet.2020.07.002. Epub 2020 Jul 28.
PMID: 32726606; PMCID: PMC7501995.
In vivo protocol:
1. Thielen LA, Chen J, Jing G, Moukha-Chafiq O, Xu G, Jo S, Grayson TB, Lu B, Li P, Augelli-Szafran CE, Suto MJ, Kanke M,
Sethupathy P, Kim JK, Shalev A. Identification of an Anti-diabetic, Orally Available Small Molecule that Regulates TXNIP
Expression and Glucagon Action. Cell Metab. 2020 Sep 1;32(3):353-365.e8. doi: 10.1016/j.cmet.2020.07.002. Epub 2020 Jul 28.
PMID: 32726606; PMCID: PMC7501995.
1: Xie WM, Su W, Liu XY, Zhou J, Wang M, Wang Y, Wang W, Bai X, Li Z, Li T. FTO Deficiency Alleviates LPS-induced Acute Lung Injury by TXNIP/NLRP3-mediated Alveolar Epithelial Cell Pyroptosis. Am J Respir Cell Mol Biol. 2024 May;70(5):351-363. doi: 10.1165/rcmb.2023-0251OC. PMID: 38271683.
2: Thielen LA, Chen J, Jing G, Moukha-Chafiq O, Xu G, Jo S, Grayson TB, Lu B, Li P, Augelli-Szafran CE, Suto MJ, Kanke M, Sethupathy P, Kim JK, Shalev A. Identification of an Anti-diabetic, Orally Available Small Molecule that Regulates TXNIP Expression and Glucagon Action. Cell Metab. 2020 Sep 1;32(3):353-365.e8. doi: 10.1016/j.cmet.2020.07.002. Epub 2020 Jul 28. PMID: 32726606; PMCID: PMC7501995.
