| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
KIN‑8194 targets HCK (hematopoietic cell kinase) and BTK (Bruton's tyrosine kinase), two key kinases in B‑cell receptor signaling. It selectively inhibits both kinases with high potency (IC50 = 0.915 nM for HCK, <0.495 nM for BTK). The compound is designed to overcome resistance to first‑generation BTK inhibitors such as ibrutinib.
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| ln Vitro |
KIN-8194 (0-1 μM, 7 days) inhibits the growth of MCL cell lines (Maver-1, JeKo-1, Mino, Rec-1 and Granta-519) and primary cells[1]. KIN-8194 (0-1 μM, 7 days) reduces the proliferation of MCL cell lines by inhibiting HCK[1]. KIN-8194 (100 nM, 6 h) inhibits the AKT-S6 signaling pathway in Maver-1 and Granta-519 cells in an HCK-dependent manner[1]. KIN-8194 (0-1 μM, 30 min) inhibits the adhesion of MCL cells (JeKo-1 and Granta-519) to fibronectin or stromal cells in an HCK-dependent manner[1].
KIN‑8194 (0‑1 microM; 7 days) inhibits the growth of BTKi‑resistant MCL cell lines (Maver‑1, JeKo‑1, Mino, Rec‑1, Granta‑519) and primary cells by inhibiting HCK. It reduces cell proliferation in a concentration‑dependent manner. KIN‑8194 (100 nM; 6 h) inhibits the AKT‑S6 signaling pathway in Maver‑1 and Granta‑519 cells in an HCK‑dependent manner, and (0‑1 microM; 30 min) inhibits adhesion of MCL cells to fibronectin or stromal cells. |
| ln Vivo |
KIN-8194 (12.5-50 mg/kg, oral, once) blocks pHCK and pBTK in a dose-dependent manner in the MYD88-mutated TMD-8 ABC DLBCL xenograft mouse model[2]. KIN-8194 (50 mg/kg, oral, daily, 6 weeks) inhibited tumor growth in a MYD88 mutant TMD-8 ABC DLBCL xenograft mouse model [2]. , 22 days) combined with Venetoclax (HY-15531) prolonged the median survival time of mice xenografted with ibrutinib-resistant BTKCys481Ser TMD-8 cells< sup>[2].
KIN‑8194 (12.5‑50 mg/kg, oral, single dose) blocks pHCK and pBTK in a dose‑dependent manner in the MYD88‑mutant TMD‑8 ABC DLBCL xenograft model. KIN‑8194 (50 mg/kg, oral, daily, 6 weeks) inhibits tumor growth in the same model. KIN‑8194 (30 mg/kg, oral, daily, 22 days) in combination with venetoclax prolongs median survival in mice bearing ibrutinib‑resistant BTKC481S TMD‑8 xenografts. |
| Enzyme Assay |
Binding affinity of KIN‑8194 to purified HCK and BTK kinases is measured by a kinase activity assay using a peptide substrate and ATP. The compound is incubated with the kinase, and after adding ATP and substrate, the remaining kinase activity is measured. IC50 values are calculated from dose‑response curves (HCK IC50 = 0.915 nM, BTK IC50 = <0.495 nM).
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| Cell Assay |
BTKi‑resistant MCL cell lines (Maver‑1, JeKo‑1, Mino, Rec‑1, Granta‑519) or ABC DLBCL cell lines (TMD‑8) are seeded in 96‑well plates and treated with KIN‑8194 at graded concentrations (0‑1 microM) for 7 days. Cell viability is measured using the CellTiter‑Glo or MTT assay to determine IC50 values. For mechanistic studies, cells are treated with 100 nM for 6 h and analyzed by Western blot for AKT‑S6 pathway proteins.
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| Animal Protocol |
For in vivo efficacy, female NSG mice bearing subcutaneous TMD‑8 xenografts (MYD88‑mutant ABC DLBCL) are treated orally with KIN‑8194 (50 mg/kg) daily for 6 weeks. Tumor volumes are measured twice weekly. For survival studies, mice bearing ibrutinib‑resistant BTKC481S TMD‑8 xenografts are treated with KIN‑8194 (30 mg/kg, oral, daily) in combination with venetoclax for 22 days, and median survival is recorded.
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| ADME/Pharmacokinetics |
KIN‑8194 (C2₈H33N₇O, MW = 483.61) is soluble in DMSO. The powder can be stored at ‑20degC for up to 3 years. For in vivo use, it can be formulated in solvents such as DMSO, PEG300, Tween‑80, and saline. Based on its oral activity, it is likely to have acceptable oral bioavailability, but detailed PK parameters (Cmax, Tmax, t1/2, AUC, etc.) are not reported in the available sources.
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| Toxicity/Toxicokinetics |
No specific toxicity data for KIN‑8194 are provided in the search results. The compound is for research use only and has not undergone formal toxicological evaluation for clinical applications. Standard laboratory safety precautions should be followed during handling. The compound is well‑tolerated at the tested doses (12.5‑50 mg/kg) in mouse xenograft models, suggesting a reasonable safety margin in preclinical settings.
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| References |
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| Additional Infomation |
KIN‑8194 is a novel, orally active dual HCK/BTK inhibitor developed to overcome resistance to ibrutinib in B‑cell malignancies. It has shown preclinical efficacy in BTKi‑resistant MCL and MYD88‑driven lymphomas. The compound is for research use only and has not yet received regulatory approval for clinical use. It represents a promising therapeutic strategy for patients who have relapsed after first‑generation BTK inhibitor therapy.
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| Molecular Formula |
C28H33N7O
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| Molecular Weight |
483.61
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| Exact Mass |
483.274
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| CAS # |
330786-01-1
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| PubChem CID |
6539953
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| Appearance |
White to off-white solid powder
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| LogP |
4.1
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
36
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| Complexity |
681
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CN1CCN(CC1)[C@H]2CC[C@@H](CC2)N3C4=NC=NC(=C4C(=N3)C5=CC=C(C=C5)OC6=CC=CC=C6)N
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| InChi Key |
RLVCBYBGVBOVFV-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C28H33N7O/c1-33-15-17-34(18-16-33)21-9-11-22(12-10-21)35-28-25(27(29)30-19-31-28)26(32-35)20-7-13-24(14-8-20)36-23-5-3-2-4-6-23/h2-8,13-14,19,21-22H,9-12,15-18H2,1H3,(H2,29,30,31)
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| Chemical Name |
1-[4-(4-methylpiperazin-1-yl)cyclohexyl]-3-(4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-4-amine
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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 | 2.0678 mL | 10.3389 mL | 20.6778 mL | |
| 5 mM | 0.4136 mL | 2.0678 mL | 4.1356 mL | |
| 10 mM | 0.2068 mL | 1.0339 mL | 2.0678 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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