| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
JAK2 Tyk2
ACK1 (Activated Cdc42-associated kinase 1, also known as TNK2). (R)-9b is a potent and selective inhibitor of ACK1, with an IC50 of 56 nM. It also exhibits weaker inhibitory activity against the JAK family kinases JAK2 and Tyk2. ACK1 is involved in cancer cell proliferation, survival, and metastasis, making it an important target in oncology research. |
|---|---|
| ln Vitro |
(R)-9b potently inhibits ACK1 tyrosine kinase with an IC50 of 56 nM. It also exhibits inhibitory effects on JAK family kinases JAK2 and Tyk2. This compound is highly selective for ACK1 compared to a large panel of other kinases, as it was designed through an innovative fragment-based approach. Its in vitro activity makes it a valuable tool for studying ACK1 signaling in cancer cells.
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| ln Vivo |
No specific in vivo data was found for (R)-9b. However, given its potent in vitro activity against ACK1, it is expected to have antitumor efficacy in vivo in animal models of hormone-regulated cancers, such as prostate and breast cancer xenografts. It is being developed as a targeted therapy for these ACK1-driven cancers.
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| Enzyme Assay |
Standard ACK1 kinase inhibition assay: Recombinant ACK1 (0.1-1 ug) is incubated in a reaction buffer (e.g., 50 mM HEPES, pH 7.5, 10 mM MgCl2, 1 mM DTT) with 10 uM ATP and a peptide substrate. Serial dilutions of (R)-9b are added. The reaction is initiated and, after incubation, the level of peptide phosphorylation is measured using a homogeneous time-resolved fluorescence (HTRF) or radiometric (32P-ATP) method. The IC50 is calculated by plotting % inhibition vs. log(concentration).
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| Cell Assay |
Standard cell-based viability assay: Cancer cells (e.g., prostate or breast cancer cell lines) are seeded in 96-well plates and allowed to attach overnight. The next day, cells are treated with increasing concentrations (0.1 nM to 10 uM) of (R)-9b for 72 hours. Cell viability is then measured using a CellTiter-Glo luminescent cell viability assay. The 50% growth inhibition (GI50) is calculated from the dose-response curve. ACK1 phosphorylation is also assessed by Western blot.
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| Animal Protocol |
No specific animal protocol was found. A typical in vivo protocol for efficacy: Female BALB/c nude mice are injected subcutaneously with human cancer cells (e.g., 5×10⁶ cells/mouse). When tumors reach an average volume of 150 mm3, mice are randomized into treatment groups. (R)-9b is administered orally or intraperitoneally at doses of 10-50 mg/kg, once daily for 21 days. Tumor size is measured twice weekly with calipers. Tumor growth inhibition (TGI) is calculated at the study endpoint.
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| ADME/Pharmacokinetics |
No specific PK data was found. As a small-molecule kinase inhibitor, (R)-9b is expected to have a favorable PK profile. The R-enantiomer is typically the more potent and stable form. The compound is likely metabolized by CYP450 enzymes, primarily in the liver. Standard PK studies would involve IV and oral dosing in rodents, with plasma samples collected over 24 hours for LC-MS/MS analysis.
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| Toxicity/Toxicokinetics |
No specific toxicity data was found. However, as a tyrosine kinase inhibitor, it may cause off-target effects such as gastrointestinal issues and fatigue. Since ACK1 is not essential for normal cell function, the compound is expected to have a manageable safety profile. Further preclinical toxicology studies are required for clinical development.
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| References | |
| Additional Infomation |
(R)-9b (CAS: 1655527-68-6) has a molecular formula of C20H27ClN6O and a molecular weight of 402.92. It appears as a white to off-white solid powder. This compound is a potent and selective ACK1 tyrosine kinase inhibitor with an IC50 of 56 nM and is used for research into hormone-regulated cancers.
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| Molecular Formula |
C20H27CLN6O
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|---|---|
| Molecular Weight |
402.92
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| Exact Mass |
402.193
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| CAS # |
1655527-68-6
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| PubChem CID |
90479825
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| Appearance |
White to off-white solid powder
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| LogP |
0
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
28
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| Complexity |
470
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| Defined Atom Stereocenter Count |
1
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| SMILES |
ClC1=CN=C(N=C1NC[C@H]1CCCO1)NC1C=CC(=CC=1)N1CCN(C)CC1
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| InChi Key |
MMJSYUQCKWEFRW-QGZVFWFLSA-N
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| InChi Code |
InChI=1S/C20H27ClN6O/c1-26-8-10-27(11-9-26)16-6-4-15(5-7-16)24-20-23-14-18(21)19(25-20)22-13-17-3-2-12-28-17/h4-7,14,17H,2-3,8-13H2,1H3,(H2,22,23,24,25)/t17-/m1/s1
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| Chemical Name |
5-chloro-2-N-[4-(4-methylpiperazin-1-yl)phenyl]-4-N-[[(2R)-oxolan-2-yl]methyl]pyrimidine-2,4-diamine
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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) |
DMSO : ~25 mg/mL (~62.05 mM; with ultrasonication)
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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 | 2.4819 mL | 12.4094 mL | 24.8188 mL | |
| 5 mM | 0.4964 mL | 2.4819 mL | 4.9638 mL | |
| 10 mM | 0.2482 mL | 1.2409 mL | 2.4819 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.
Link: https://clinicaltrials.gov/ct2/show/NCT06705686
Conditions:Metastatic Castration-resistant Prostate Cancer (CRPC)|Metastatic Castration-resistant Prostate CarcinomaProducts are for research use only; We do not sell to patients
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