Synonym
PI-273; PI273; PI 273
IUPAC/Chemical Name
2-(3-(4-chlorobenzoyl)thioureido)-4-ethyl-5-methylthiophene-3-carboxamide
InChi Key
MIERMBQDBLFAFW-UHFFFAOYSA-N
InChi Code
InChI=1S/C16H16ClN3O2S2/c1-3-11-8(2)24-15(12(11)13(18)21)20-16(23)19-14(22)9-4-6-10(17)7-5-9/h4-7H,3H2,1-2H3,(H2,18,21)(H2,19,20,22,23)
SMILES Code
O=C(C1=C(NC(NC(C2=CC=C(Cl)C=C2)=O)=S)SC(C)=C1CC)N
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:
PI-273 is a first reversibly and specific phosphatidylinositol 4-kinase (PI4KIIα) inhibitor with an IC50 of 0.47 μM.
In vitro activity:
2-(3-(4-Chlorobenzoyl)thioureido)-4-ethyl-5-methylthiophene-3-carboxamide (PI-273) exhibited the greatest inhibitory effect on PI4KIIα kinase activity (IC50 = 0.47 μmol/L) and suppressed cell proliferation. Surface plasmon resonance and thermal shift assays indicated that PI-273 interacted directly with PI4KIIα. Kinetic analysis identified PI-273 as a reversible competitive inhibitor with respect to the substrate phosphatidylinositol (PI), which contrasted with most other PI kinase inhibitors that bind the ATP binding site. PI-273 reduced PI4P content, cell viability, and AKT signaling in wild-type MCF-7 cells, but not in PI4KIIα knockout MCF-7 cells, indicating that PI-273 is highly selective for PI4KIIα.
Reference: Cancer Res. 2017 Nov 15;77(22):6253-6266. https://pubmed.ncbi.nlm.nih.gov/28827373/
In vivo activity:
Importantly, PI-273 significantly inhibited MCF-7 cell-induced breast tumor growth in mice without toxicity. PI-273 is the first substrate-competitive, subtype-specific inhibitor of PI4KIIα, the use of which will facilitate evaluations of PI4KIIα as a cancer therapeutic target.
Reference: Cancer Res. 2017 Nov 15;77(22):6253-6266. https://pubmed.ncbi.nlm.nih.gov/28827373/
|
Solvent |
mg/mL |
mM |
comments |
| Solubility |
| DMSO |
6.0 |
15.74 |
|
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
381.89
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:
Li J, Gao Z, Zhao D, Zhang L, Qiao X, Zhao Y, Ding H, Zhang P, Lu J, Liu J, Jiang H, Luo C, Chen C. PI-273, a Substrate-Competitive, Specific Small-Molecule Inhibitor of PI4KIIα, Inhibits the Growth of Breast Cancer Cells. Cancer Res. 2017 Nov 15;77(22):6253-6266. doi: 10.1158/0008-5472.CAN-17-0484. Epub 2017 Aug 21. PMID: 28827373.
In vitro protocol:
Li J, Gao Z, Zhao D, Zhang L, Qiao X, Zhao Y, Ding H, Zhang P, Lu J, Liu J, Jiang H, Luo C, Chen C. PI-273, a Substrate-Competitive, Specific Small-Molecule Inhibitor of PI4KIIα, Inhibits the Growth of Breast Cancer Cells. Cancer Res. 2017 Nov 15;77(22):6253-6266. doi: 10.1158/0008-5472.CAN-17-0484. Epub 2017 Aug 21. PMID: 28827373.
In vivo protocol:
Li J, Gao Z, Zhao D, Zhang L, Qiao X, Zhao Y, Ding H, Zhang P, Lu J, Liu J, Jiang H, Luo C, Chen C. PI-273, a Substrate-Competitive, Specific Small-Molecule Inhibitor of PI4KIIα, Inhibits the Growth of Breast Cancer Cells. Cancer Res. 2017 Nov 15;77(22):6253-6266. doi: 10.1158/0008-5472.CAN-17-0484. Epub 2017 Aug 21. PMID: 28827373.
1: Li J, Gao Z, Zhao D, et al. PI-273, a Substrate-Competitive, Specific Small-Molecule Inhibitor of PI4KIIα, Inhibits the Growth of Breast Cancer Cells. Cancer Res. 2017;77(22):6253-6266. doi:10.1158/0008-5472.CAN-17-0484
2: Shi, L., Tan, X., Liu, X., Yu, J., Bota-Rabassedas, N., Niu, Y., ... & Kurie, J. M. (2021). Addiction to Golgi-resident PI4P synthesis in chromosome 1q21. 3–amplified lung adenocarcinoma cells. Proceedings of the National Academy of Sciences, 118(25), e2023537118.
