JDB175 is a selective BTK inhibitor (antagonist) with oral activity and excellent BBB (blood-brain barrier) penetration. JDB175 showed good activity in the central nervous system/CNS lymphoma mouse model without obvious signs of toxicity. It effectively inhibited the proliferation of human lymphoma cells through the BTK signaling pathway, induced cell cycle arrest, and promoted cell apoptosis.

Physicochemical Properties

Molecular Formula	C26H21F3N4O2
Molecular Weight	478.47
CAS #	2635328-79-7
Appearance	Typically exists as solid at room temperature
HS Tariff Code	2934.99.9001
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)

Biological Activity

ln Vitro	DB175 (15–40 μM, 48 h) can efficiently suppress BTK phosphorylation, downregulate cyclin D1 and CDK2 expression, and upregulate P21 expression in Namalwa and Raji cells [1]. In Namalwa, SU-DHL-4, Raji, Ramos, and TMD-8 cells, JDB175 (0-60 μM, 48 h, 72 h) exhibits time- and dose-dependent inhibitory effects on cell survival [1]. In Namalwa, SU-DHL-4, Raji, and Ramos cells, JDB175 (15 μM, 48 h) markedly increased G0/G1 phase distribution [1]. In Namalwa, SU-DHL-4, Raji, and Ramos cells, JDB175 (20–40 μM, 72 h) exhibits potent apoptosis-inducing activities [1].
ln Vivo	JDB175 (10 mg/kg, oral, 0.5 h) inhibits central nervous system lymphoma in rats well and has a great capacity to cross the blood-brain barrier[1]. JDB175 (oral, 150 mg/kg, 3 days) shows good safety and efficient tumor suppression in a nude mice model of central nervous system lymphoma[1].
Cell Assay	Cell Viability Assay[1] Cell Types: Namalwa, SU-DHL-4, Raji, Ramos, TMD-8 Tested Tested Concentrations: 0-60 μM Incubation Duration: 48 and 72 hrs (hours) Experimental Results: Inhibited the cell viability in a time - and dose- dependent manner. The IC50 values of all four cell lines were below 20 µM after 48 h, and further diminished after 24 h . Western Blot Analysis[1] Cell Types: Namalwa, Raji Tested Tested Concentrations: 15-40 μM Incubation Duration: 48 hrs (hours) Experimental Results: Inhibited the phosphorylation of BTK, down-regulated the expression of cyclin D1 and CDK2, and up-regulated the expression of P21 in both cell lines. Cell Cycle Analysis[1] Cell Types: Namalwa, SU-DHL-4, Raji, Ramos Tested Tested Concentrations: 15 μM Incubation Duration: 48 hrs (hours) Experimental Results: G0/G1 phase increased dramatically, from 22.6% in the drug-loaded group to 36.7% in Namalwa cells. Similar changes were also observed in Raji, SU-DHL-4 and Ramos cells. Apoptosis Analysis[1] Cell Types: Namalwa,SU-DHL-4,Raji,Ramos Tested Tested Concentrations: 20 and 40 μM Incubation Duration: 72 hrs (hours) Experimental Results: Induced more than 5
Animal Protocol	Animal/Disease Models: Central nervous system lymphoma tumor model in rat[1] Doses: 10 mg/kg Route of Administration: po (oral gavage) Experimental Results: Increased the brain penetration rate (%, Cbrain/Cplasma). Animal/Disease Models: Central nervous system lymphoma tumor model in nude mice[1] Doses: 150 mg/kg Route of Administration: po (oral gavage) Experimental Results: Inhibited tumor growth in heart, liver, lung and kindy.
References	[1]. Xia Y, et al. A novel Bruton's tyrosine kinase inhibitor JDB175 shows potent efficacy to suppress central nervous system lymphoma. MedComm (2020). 2023 Nov 4;4(6):e424.

Solubility Data

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

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 (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *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). 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)] *Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL 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). Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.0900 mL	10.4500 mL	20.9000 mL
	5 mM	0.4180 mL	2.0900 mL	4.1800 mL
	10 mM	0.2090 mL	1.0450 mL	2.0900 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.