PI-273 is the first reversible and specific phosphatidylinositol 4-kinase (PI4KIIα) inhibitor (antagonist) with IC50 of 0.47 μM. PI-273 can inhibit the proliferation of breast cancer cells, block the cell cycle and cause apoptosis.

Physicochemical Properties

Molecular Formula	C16H16CLN3O2S2
Molecular Weight	381.900139808655
Exact Mass	381.037
CAS #	925069-34-7
PubChem CID	17168969
Appearance	Light yellow to yellow solid powder
LogP	4.2
Hydrogen Bond Donor Count	3
Hydrogen Bond Acceptor Count	4
Rotatable Bond Count	4
Heavy Atom Count	24
Complexity	498
Defined Atom Stereocenter Count	0
SMILES	O=C(C1C(CC)=C(C)SC=1NC(NC(C1C=CC(Cl)=CC=1)=O)=S)N
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)
Chemical Name	2-[(4-chlorobenzoyl)carbamothioylamino]-4-ethyl-5-methylthiophene-3-carboxamide
HS Tariff Code	2934.99.9001
Storage	Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Shipping Condition	Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Biological Activity

Targets	PI4KIIα 0.47 μM (IC50)
ln Vitro	At the G2-M phase, PI-273 (2 μM; 48 hours) inhibits the cell cycle[1]. All three Ras wild-type breast cancer cells (MCF-7, T-47D, and SK-BR-3) undergo cell apoptosis when exposed to PI-273 (2 μM) for 48 hours[1]. AKT signaling pathway suppression is possible with PI-273 (0.5-2 μM; for 3 days) in a dose- and time-dependent way[1]. Both MCF-7 and T-47D cell proliferation is inhibited in a time-dependent manner by PI-273 at 1 μM and 2 μM [1].
ln Vivo	In MCF-7 xenografts, PI-273 (intraperitoneal injection; 25 mg/kg/day; 15 days) significantly inhibits the tumor weight and volume[1]. The absolute bioavailability of PI-273 is 5.1%[1]. Its half-lives are 0.411 hours for intravenous treatment and 1.321 hours for intragastric administration (0.5 mg/kg intravenously or 1.5 mg/kg intragastrically; 0.08-5 hours).
Cell Assay	Cell Cycle Analysis[1] Cell Types: MCF-7, T-47D, SK-BR-3, MDA-MB-231, SUM229PE, Hs 578T cells Tested Concentrations: 2 μM Incubation Duration: 48 hrs (hours) Experimental Results: Blocked the cell cycle at the G2-M phase. Apoptosis Analysis[1] Cell Types: MCF-7, T-47D, and SK-BR-3 cells Tested Concentrations: 2 μM Incubation Duration: 48 hrs (hours) Experimental Results: Induced cell apoptosis in all three Ras wild-type breast cancer cells: MCF-7, T-47D, and SK-BR-3. Western Blot Analysis[1] Cell Types: MCF-7 cells Tested Concentrations: 0.5, 1, 2 μM Incubation Duration: For 3 days Experimental Results: Suppressed the AKT signaling pathway in a dose- and time-dependent manner.
Animal Protocol	Animal/Disease Models: Eightweeks old male BALB/c nude mice with MCF-7 cell[1] Doses: 25 mg/kg Route of Administration: intraperitoneal (ip)injection; daily; 15 days Experimental Results: Suppressed the tumor volume and weight in the MCF-7 xenografts. Animal/Disease Models: Male SD (Sprague-Dawley) rats[1] Doses: 0.5 mg/kg (intravenously (iv)) or 1.5 mg/kg (intragastrically (po)) (pharmacokinetic/PK Study) Route of Administration: intravenously (iv) or intragastrically (po); 0.08, 0.16, 0.33, 0.67, 1, 1.5, 2, 3 and 5 hrs (hours) Experimental Results: Has a half-life of 0.411 hrs (hours) for intravenous (iv)administration and 1.321 hrs (hours) for intragastric (po)administration, and the absolute bioavailability of PI-273 is 5.1 %.
References	[1]. 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.

Solubility Data

Solubility (In Vitro)

DMSO : 6.02 mg/mL (15.76 mM)

Solubility (In Vivo)

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples. Injection Formulations (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] *Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Oral Formulations Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.6185 mL	13.0924 mL	26.1849 mL
	5 mM	0.5237 mL	2.6185 mL	5.2370 mL
	10 mM	0.2618 mL	1.3092 mL	2.6185 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.