| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
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| 10mg | |||
| Other Sizes |
Purity: ≥98%
| Targets |
Akt
API-1 targets Akt (also known as protein kinase B), a key serine/threonine kinase in the PI3K/Akt signaling pathway that promotes cell survival and proliferation. It binds to the pleckstrin homology (PH) domain of Akt, which is critical for its membrane translocation and activation. This binding inhibits the EGF-induced kinase activity of Akt1, Akt2, and Akt3. |
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| ln Vitro |
An isosteric scaffold of adenosine, the 4-aminopyrido[2,3-d]pyrimidine derivative API-1 was discovered to inhibit Akt by screening the DTP/NCI compound library in a cell-based assay. API-1 binds to the PH domain and inhibits Akt membrane translocation, leading to the inhibition of the growth of tumors with hyperactivated Akt. API-1 was shown to induce apoptosis in tested cancer cell lines by synergizing with TNF-related apoptosis-inducing ligand (TRAIL). A series of 4-amino-pyrrolo[2,3-d]pyrimidine derivatives, closely related to API-1, were discovered in a high-throughput screening based on a newly developed fluorescence-based assay as allosteric Akt inhibitors [1].
In vitro, API-1 inhibits EGF-induced kinase activity of Akt1, Akt2, and Akt3. With an IC50 of about 0.8 μM, it effectively reduces the levels of Akt phosphorylation. It induces cell growth arrest and apoptosis in human cancer cells expressing constitutively active Akt. In API-1-sensitive lung cancer cell lines, it quickly and effectively decreases Mcl-1 levels. |
| ln Vivo |
In vivo, API-1 has demonstrated antitumor activity. It inhibits the growth of tumors with hyperactivated Akt. Its ability to induce apoptosis and inhibit tumor growth has been observed in preclinical models. However, specific details of in vivo studies are not extensively detailed in the available literature.
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| Enzyme Assay |
The in vitro binding assay for API-1 involves studying its interaction with the PH domain of Akt. Techniques such as surface plasmon resonance (SPR) or nuclear magnetic resonance (NMR) can be used to confirm binding. Competitive binding assays with fluorescently labeled PH domain ligands can also be used to determine the compound's affinity for the PH domain.
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| Cell Assay |
In vitro cellular assays for API-1 assess its functional activity as an Akt inhibitor. Cancer cell lines are treated with API-1, and the phosphorylation of Akt and its downstream targets (e.g., GSK3β, PRAS40) is measured by Western blot. Cell proliferation, apoptosis, and Mcl-1 levels are also assessed. These assays demonstrate the compound's ability to inhibit Akt signaling and induce cell death.
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| Animal Protocol |
In vivo animal studies for API-1 have been conducted in xenograft models to evaluate its antitumor efficacy. Tumor-bearing mice are treated with API-1, and tumor growth is monitored. Markers of apoptosis and Akt signaling are assessed in tumor tissues. However, specific details of these studies are not extensively detailed in the available literature.
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| ADME/Pharmacokinetics |
API-1 is a cell-permeable small molecule that is typically administered via injection in in vivo studies. Its pharmacokinetic properties are characteristic of small molecule kinase inhibitors. However, detailed parameters such as half-life, volume of distribution, and bioavailability are not extensively detailed in the available literature. It is intended for research use only.
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| Toxicity/Toxicokinetics |
Specific toxicity data for API-1 are not extensively detailed in the available literature. As an Akt inhibitor, its toxicity profile is likely related to its mechanism of action. However, its ability to induce apoptosis in cancer cells suggests potential for therapeutic use. It is intended for research purposes only and is not for human use.
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| References | |
| Additional Infomation |
Screening of the National Cancer Institute (NCI) Diverse Compound Library revealed API-2 [(Tricilidine (TCN), NSC 154020)], which effectively inhibits the Akt signaling pathway in human cancer cells, thereby suppressing cell growth and inducing apoptosis. TCN is a tricyclic purine nucleoside derivative (Figure 9), which is activated intracellularly by adenosine kinase metabolism to the monophosphate-active analog TCN-P. Surface plasmon resonance and nuclear magnetic resonance spectroscopy analysis showed that TCN-P (not TCN) binds to the region near the PIP3 binding pocket in the PH domain of Akt, thereby preventing Akt phosphorylation and subsequent activation. The mechanism by which TCN-P inhibits Akt may be by preventing PIP3 from recruiting Akt to the plasma membrane. This mechanism may involve competing with PIP3 for binding to the PH domain, or by binding to regions that induce conformational changes, thereby hindering PIP3 activation. Studies have shown that 10 μM TCN can inhibit the phosphorylation of Akt and its downstream signaling pathways in T cell acute lymphoblastic leukemia cells, leading to cell cycle arrest and caspase-dependent apoptosis. In prostate cancer cells, TCN can enhance apoptosis induced by the death receptor pathway (124). TCN and TCN-P have been used in several clinical trials for various solid tumors and hematological malignancies, but their efficacy is limited due to their toxicity. TCN combined with other anticancer drugs is more effective than TCN alone [1].
API-1 is a potent and selective Akt inhibitor that binds to the PH domain, a unique mechanism of action compared to ATP-competitive inhibitors. It is a valuable research tool for studying the PI3K/Akt pathway and its role in cancer cell survival and proliferation. It is not approved for clinical use and is intended for research purposes only. |
| Molecular Formula |
C13H15N5O6
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|---|---|
| Molecular Weight |
337.2881
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| Exact Mass |
337.102
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| Elemental Analysis |
C, 46.29; H, 4.48; N, 20.76; O, 28.46
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| CAS # |
36707-00-3
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| Related CAS # |
36707-00-3
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| PubChem CID |
24773090
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| Appearance |
white solid powder
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| Density |
1.792g/cm3
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| Boiling Point |
795.8ºC at 760 mmHg
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| Flash Point |
435.1ºC
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| Index of Refraction |
1.764
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| LogP |
-1.9
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| Hydrogen Bond Donor Count |
5
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| Hydrogen Bond Acceptor Count |
10
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| Rotatable Bond Count |
3
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| Heavy Atom Count |
24
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| Complexity |
571
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| Defined Atom Stereocenter Count |
4
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| SMILES |
NC(C1C(=O)C2=C(N=CN=C2N)N(C2C(O)C(O)C(CO)O2)C=1)=O
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| InChi Key |
SPBWHPXCWJLQRU-FITJORAGSA-N
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| InChi Code |
InChI=1S/C13H15N5O6/c14-10-6-7(20)4(11(15)23)1-18(12(6)17-3-16-10)13-9(22)8(21)5(2-19)24-13/h1,3,5,8-9,13,19,21-22H,2H2,(H2,15,23)(H2,14,16,17)/t5-,8-,9-,13-/m1/s1
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| Chemical Name |
4-amino-8-[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-5-oxopyrido[2,3-d]pyrimidine-6-carboxamide
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| Synonyms |
API1; NSC 177233;API-1; NSC-177233; api-1; 36707-00-3; NSC 177223; 4-Amino-5,6,7,8-tetrahydro-5-oxo-8-(beta-D-ribofuranosyl)pyrido[2,3-d]pyrimidine-6-carboxamide; W3UEK36Q7X; NSC177223; 4-amino-5,8-dihydro-5-oxo-8-beta-d-ribofuranosyl-pyrido[2,3-d]pyrimidine-6-carboxamide; ld-101; API 1; NSC177233
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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 |
| 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) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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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 | 2.9648 mL | 14.8240 mL | 29.6481 mL | |
| 5 mM | 0.5930 mL | 2.9648 mL | 5.9296 mL | |
| 10 mM | 0.2965 mL | 1.4824 mL | 2.9648 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.
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