| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 25mg |
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| 50mg |
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| 100mg |
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Purity: ≥98%
ETP-46321 is a novel, potent and orally bioavailable inhibitor of PI3Kα and PI3Kδ with Kiapp values of 2.3 nM and 14.2 nM, respectively in biochemical assays. PI3K is a crucial target for cancer therapeutics because a variety of human cancers exhibit deregulation of this signaling pathway. In a GEMM mouse tumor model fueled by a K-Ras(G12V) oncogenic mutation, TP-46321 PK/PD studies revealed time-dependent downregulation of AKT(Ser473) phosphorylation, which correlates with compound levels in tumor tissue. ETP-46321 therapy significantly slowed the growth of the tumor.
| Targets |
p110α (Ki = 2.3 nM); PI3Kα-E545K (Ki = 1.77 nM); PI3Kα-E542K (Ki = 1.89 nM); ; p110δ (Ki = 14.2 nM); p110β (Ki = 170 nM); p110γ (Ki = 179 nM)
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| ln Vitro |
The PI3K isoform ETP-46321 is chosen for screening. ETP-46321 has a higher Kiapp value (2.3 nM) than isoform. With regard to mTOR and 288 representative kinases, ETP-4632 has been profiled and demonstrated to be a potent PI3K α and δ inhibitor and kinase. ETP-46321 is also tested against three p110 mutant enzymes identified in human cancers (E542K, E545K, and H1047R), and it is equally potent against these mutants as the wild-type protein (Kiapp=2.33, 1.77, and 1.89 nM for PI3Kα-H1047R, PI3Kα-E545K, respectively). In the U2OS cell line, ETP-46321 has an IC50 of 8.3 nM, which inhibits the phosphorylation of AKT.
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| ln Vivo |
ETP-46321, is selected for in vivo studies based on its appealing pharmacokinetic profile in BALB-C mice, low in vivo Clearance (0.6 L/h/Kg) and good oral bioavailability (90%). ETP-46321 exhibits a favorable pharmacokinetic profile in mice and is chosen for preliminary in vivo testing in a lung tumor mouse model driven by the K-RasG12V oncogenic mutation. PET imaging techniques show significant tumor growth inhibition and a decrease in tumor metabolic activity[1].
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| Animal Protocol |
Mice; ETP-46321 (50 mg/kg, p.o.) is administered to BALB/C mice every day for three weeks. Four mice from each treatment group had their tumor volumes measured and compared to the initial volume at the start of the treatment.
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| References |
| Molecular Formula |
C20H27N9O3S
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|---|---|---|
| Molecular Weight |
473.55
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| Exact Mass |
473.196
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| Elemental Analysis |
C, 50.73; H, 5.75; N, 26.62; O, 10.14; S, 6.77
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| CAS # |
1252594-99-2
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| Related CAS # |
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| PubChem CID |
46927938
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| Appearance |
White to off-white solid powder
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| LogP |
1.285
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
11
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
33
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| Complexity |
746
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| Defined Atom Stereocenter Count |
0
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| SMILES |
S(C([H])([H])[H])(N1C([H])([H])C([H])([H])N(C([H])([H])C2=C([H])N3C([H])=C(C4=C([H])N=C(N([H])[H])N=C4[H])N=C(C3=N2)N2C([H])([H])C([H])([H])OC([H])([H])C2([H])[H])C([H])([H])C1([H])[H])(=O)=O
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| InChi Key |
OHKDVDMWRKFZRB-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C20H27N9O3S/c1-33(30,31)29-4-2-26(3-5-29)12-16-13-28-14-17(15-10-22-20(21)23-11-15)25-19(18(28)24-16)27-6-8-32-9-7-27/h10-11,13-14H,2-9,12H2,1H3,(H2,21,22,23)
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| Chemical Name |
5-[2-[(4-methylsulfonylpiperazin-1-yl)methyl]-8-morpholin-4-ylimidazo[1,2-a]pyrazin-6-yl]pyrimidin-2-amine
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| Synonyms |
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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| 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
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *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). View More
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)] 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). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.1117 mL | 10.5585 mL | 21.1171 mL | |
| 5 mM | 0.4223 mL | 2.1117 mL | 4.2234 mL | |
| 10 mM | 0.2112 mL | 1.0559 mL | 2.1117 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.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
Bioorg Med Chem Lett.2012 May 15;22(10):3460-6. |
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