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| Other Sizes |
| Targets |
PDK1-IN-1 targets 3-phosphoinositide-dependent protein kinase 1 (PDK1), a serine/threonine kinase that phosphorylates and activates AKT (PKB), SGK, and other AGC family kinases. PDK1 is a key node in the PI3K signaling pathway, regulating cell growth, proliferation, survival, metabolism, and migration. PDK1-IN-1 also inhibits FGFR3, NTRK3, RP-S6K, and WEE1 (off-target activities). It also selectively inhibits microtubule affinity-regulating kinases (MARKs), which are implicated in Alzheimer‘s disease (tau phosphorylation). The compound thus has multiple potential applications beyond cancer.
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| ln Vitro |
In vitro, PDK1-IN-1 (Compound 2-11) inhibits PDK1 kinase activity. No specific IC50 value for PDK1 is reported in the search results. The compound also shows inhibitory activity against several other kinases, including FGFR3, NTRK3, RP-S6K, WEE1, and microtubule affinity-regulating kinases (MARKs). No cellular activity data (e.g., inhibition of AKT phosphorylation in cancer cells, anti-proliferative IC50 values) are reported. The compound is a tool for studying the role of PDK1 and related kinases in cell signaling and disease. Further biochemical and cellular characterization is needed.
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| ln Vivo |
No in vivo activity data for PDK1-IN-1 are reported in the search results. As a PDK1 inhibitor with additional activity against MARKs (involved in tau phosphorylation), PDK1-IN-1 could potentially be evaluated in vivo in tumor xenograft models for cancer (inhibition of PI3K/PDK1/AKT pathway leads to growth inhibition) and in tauopathy models for Alzheimer‘s disease (MARK inhibition may reduce tau hyperphosphorylation). However, no such in vivo data are provided in the search results. The compound can be used for research of myeloproliferative disorders, cancer, and Alzheimer's disease as stated, but specific efficacy data are lacking.
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| Enzyme Assay |
Binding affinity of PDK1-IN-1 to PDK1 is measured by standard in vitro kinase activity assays using purified recombinant human PDK1 and a peptide substrate (e.g., PDKtide, derived from the PDK1 docking site) in the presence of ATP (including gamma-32P-ATP for radiometric assays or using non-radioactive ADP-Glo™ assays). The compound is incubated with PDK1 for 10-30 min before adding ATP and substrate. After incubation, the reaction is stopped, and the amount of phosphorylated substrate or ADP produced is quantified. IC50 values are calculated from dose-response curves (0.001-100 microM). No IC50 value is reported. For selectivity studies, the compound is tested against a panel of kinases (e.g., FGFR3, NTRK3, RP-S6K, WEE1, MARKs) using similar assays, with reported inhibitory activity.
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| Cell Assay |
No cellular experiments for PDK1-IN-1 are described in the search results. For cellular PDK1 inhibition studies, cancer cell lines with hyperactivated PI3K/AKT signaling (e.g., PTEN-null PC3, U87MG, or PIK3CA-mutant MCF-7, HCT116) would be seeded in 6- or 96-well plates and treated with PDK1-IN-1 at graded concentrations (0.1-100 microM) for 2-24 h. Cell lysates would be analyzed by Western blot for phospho-AKT (Thr308, a direct PDK1 substrate, and Ser473), phospho-SGK, and phospho-S6K. Cell viability would be assessed by MTT or CellTiter-Glo after 48-72 h of treatment. For MARK-related studies, neuronal cell lines (e.g., SH-SY5Y) would be treated, and tau phosphorylation at MARK-specific sites would be assessed. No such data are reported.
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| Animal Protocol |
No animal experiments for PDK1-IN-1 are described in the search results. For in vivo evaluation in cancer, 6-8-week-old female BALB/c nude mice bearing subcutaneous tumor xenografts of PTEN-null or PIK3CA-mutant cancer cell lines would be treated orally or intraperitoneally with PDK1-IN-1 at doses of 10-100 mg/kg daily for 2-4 weeks. Tumor volumes would be measured, and tumors would be analyzed for pAKT (Thr308 and Ser473) and downstream markers (pS6, pGSK3beta). For Alzheimer‘s disease studies, transgenic tauopathy mice (e.g., P301S, rTg4510) could be treated, and tau phosphorylation, neurofibrillary tangle burden, and cognitive function would be assessed. No such data are provided.
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| ADME/Pharmacokinetics |
PDK1-IN-1 (6-Bromo-4-methoxypyrazolo[1,5-a]pyridine-3-carbonitrile, C₉H₆BrN3O, MW = 252.07) is a solid powder. For storage, the compound should be kept at -20degC sealed, away from moisture and light. For in vitro use, stock solutions in DMSO (10-50 mM) can be stored at -80degC for up to 6 months or at -20degC for 1 month. Solubility in water is low. For in vivo use, it can be formulated in 5% DMSO / 5% Tween-80 / 90% saline, 10% DMSO / 90% corn oil, or other vehicles. Purity is typically 97% (HPLC). No detailed PK parameters (oral bioavailability, Cmax, Tmax, half-life, brain penetration) are reported.
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| Toxicity/Toxicokinetics |
No specific toxicity data for PDK1-IN-1 are reported in the search results. As a research-grade compound, it is not intended for human use. Standard laboratory safety precautions for handling kinase inhibitors should be followed. PDK1 is a critical kinase involved in insulin signaling and cell survival; systemic inhibition of PDK1 may cause significant on-target toxicity, including hyperglycemia (due to impaired insulin signaling), metabolic disturbances, and potential organ toxicity. However, no formal toxicity studies (LD50, target organ toxicity) have been reported for PDK1-IN-1.
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| References | |
| Additional Infomation |
PDK1-IN-1 (Compound 2-11) is a research-grade small-molecule PDK1 inhibitor with additional activity against several other kinases including FGFR3, NTRK3, RP-S6K, WEE1, and microtubule affinity-regulating kinases (MARKs). MARKs are involved in tau phosphorylation and are implicated in Alzheimer‘s disease, making PDK1-IN-1 a potential tool for studying both cancer (via PDK1 inhibition) and neurodegenerative disease (via MARK inhibition). PDK1 is a master activator of the PI3K/AKT pathway, which is one of the most frequently dysregulated pathways in human cancer. The compound has not entered clinical trials or received regulatory approval for any indication. It was reported in a patent by Jason Katz et al. (Therapeutic compounds). CAS 1207836-10-9. The compound is for research use only and is not for human use. Further optimization may be needed to improve potency and selectivity for specific therapeutic applications. It is available from multiple chemical suppliers with catalog numbers .
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| Molecular Formula |
C9H6BRN3O
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|---|---|
| Molecular Weight |
252.07
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| Exact Mass |
250.969
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| CAS # |
1207836-10-9
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| PubChem CID |
58404898
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| Appearance |
Solid powder
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| Density |
1.7±0.1 g/cm3
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| Index of Refraction |
1.674
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| LogP |
1.92
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
3
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| Rotatable Bond Count |
1
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| Heavy Atom Count |
14
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| Complexity |
264
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| Defined Atom Stereocenter Count |
0
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| SMILES |
BrC1C=C(C2=C(C#N)C=NN2C=1)OC
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| InChi Key |
JTEWRYBKHXGXHP-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C9H6BrN3O/c1-14-8-2-7(10)5-13-9(8)6(3-11)4-12-13/h2,4-5H,1H3
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| Chemical Name |
6-bromo-4-methoxypyrazolo[1,5-a]pyridine-3-carbonitrile
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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 | 3.9672 mL | 19.8358 mL | 39.6715 mL | |
| 5 mM | 0.7934 mL | 3.9672 mL | 7.9343 mL | |
| 10 mM | 0.3967 mL | 1.9836 mL | 3.9672 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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