| Size | Price | Stock | Qty |
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| Targets |
IC50: 1.1 nM (BTK), 99 nM (TEC), and 621 nM (EGFR)[1]
BGB-8035 targets Bruton's tyrosine kinase (BTK) with high selectivity. It has IC50 values of 1.1 nM, 99 nM, and 621 nM for BTK, TEC, and EGFR, respectively, demonstrating its selectivity for BTK over other kinases. By inhibiting BTK, it disrupts B-cell receptor signaling and downstream pathways involved in B-cell proliferation and survival. The compound's high selectivity for BTK over other kinases is a key feature of its pharmacological profile. |
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| ln Vitro |
For HEK293 and Ramos cells, BGB-8035 is practically non-toxic (IC50>10 μM)[1]
BGB-8035 demonstrates potent in vitro activity as a BTK inhibitor with an IC50 of 1.1 nM for BTK. It exhibits high selectivity for BTK over TEC (IC50=99 nM) and EGFR (IC50=621 nM). This compound displays antitumor activity in vitro. In cell-based assays, BGB-8035 inhibits BTK phosphorylation and downstream signaling events in B-cell lines. Its ability to inhibit BCR-induced proliferation and survival of B cells is a measure of its cellular potency. |
| ln Vivo |
The anticancer efficacy of BGB-8035 (7.5, 15, 30 mg/kg; gavage; twice daily; 16 days) is dose-dependent[1]. BGB-8035: gavage; 1, 3, 10, 30 mg/kg; twice daily; 13 days prevents weight loss associated with the CIA model and suppresses arthritis in the 8–9-week-old Lewis rat CIA model in a dose-dependent manner[1]. BGB-8035's pharmacokinetic parameters in rats and dogs[1]. Rats (IV; 1 mg/kg) Rats (5 mg/kg; PO) Canines (IV; 1 mg/kg) Dogs (2.5 mg/kg; PO) T1/2 (hour) 2.5 CL (mL/min/kg) at 1.0 6.89 Vss (L/kg) = 24.4 0.25 0.42 Cmax (ng/mL) 0.9 0.74 Tmax (h) 667 AUCinf (1246 h*ng/mL) F (%) 26.4 43 964 2645
BGB-8035 exhibits in vivo antitumor and anti-arthritis activity. In 9-week-old female NOD/SCID mice bearing REC-1 MCL xenografts, BGB-8035 (at doses of 7.5, 15, 30 mg/kg; oral administration; twice daily) showed dose-dependent antitumor activity, with corresponding tumor growth inhibition (TGI) values of 64.1%, 73.6%, and 79.9%. As an orally active compound, it has been evaluated in preclinical models of B-cell malignancies and autoimmune diseases. Its activity is attributed to its potent and selective inhibition of BTK. |
| Enzyme Assay |
The in vitro enzyme/receptor binding (non-cell-based) assay for BGB-8035 involves assessing its inhibition of BTK kinase activity. Recombinant BTK is incubated with the compound, ATP, and a substrate peptide. Kinase activity is measured by detecting the phosphorylation of the substrate. The IC50 value of 1.1 nM is determined from dose-response curves. Selectivity profiling against other kinases such as TEC and EGFR is also performed. The compound's binding affinity to BTK can be assessed using surface plasmon resonance (SPR).
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| Cell Assay |
The in vitro cell-based assay for BGB-8035 involves treating BTK-dependent cell lines with the compound and measuring the inhibition of BTK signaling. Cells are treated with varying concentrations of the compound, and the phosphorylation of BTK and its downstream substrates is assessed by Western blotting or ELISA. The compound's ability to inhibit cell proliferation is also measured. The IC50 for inhibition of BTK phosphorylation in cells is determined from dose-response curves.
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| Animal Protocol |
Animal/Disease Models: Female NOD/SCID (severe combined immunodeficient) mouse at 9 weeks of age with REC-1 MCL xenografts[1]
Doses: 7.5, 15, 30 mg/kg Route of Administration: PO; BID; 16 days Experimental Results: Demonstrated dose -dependent antitumor activity, with TGI values of 64.1, 73.6, and 79.9%, respectively. In vivo animal experiments for BGB-8035 are conducted in tumor xenograft models and models of autoimmune diseases, such as arthritis. In REC-1 MCL xenograft models, tumor-bearing mice are administered the compound orally at doses of 7.5, 15, 30 mg/kg twice daily. Tumor growth inhibition is monitored to assess the compound's efficacy. In models of arthritis, the reduction in disease severity is measured. Pharmacodynamic markers, such as BTK phosphorylation in tumor tissues, are measured to confirm target engagement. |
| ADME/Pharmacokinetics |
BGB-8035 is an orally active compound. It has a molecular weight of 453.53 g/mol and a molecular formula of C24H31N5O4. It is soluble in DMSO at 91 mg/mL. In vivo formulation can be prepared using 5% DMSO + 40% PEG300 + 5% Tween80 + 50% ddH2O or 5% DMSO + 95% Corn oil. The compound is typically stored as a powder at -20°C for up to 3 years.
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| Toxicity/Toxicokinetics |
As a research compound, its safety profile is evaluated in standard cytotoxicity and acute toxicity assays. The compound is classified for research use only and is not intended for human therapeutic use. Comprehensive toxicological characterization would be required prior to any clinical development. The compound is typically handled with standard laboratory safety precautions.
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| References | |
| Additional Infomation |
BGB-8035 (CAS 2283349-24-4) is an orally active, highly selective BTK inhibitor. It has a molecular weight of 453.53 and a molecular formula of C24H31N5O4. It exhibits antitumor and anti-arthritis activity. It is not approved for clinical use and is available only for research purposes. The compound's chemical name is not readily available, but it is known by the alias BGB8035.
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| Molecular Formula |
C24H31N5O4
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|---|---|
| Molecular Weight |
453.53
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| Exact Mass |
453.237
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| CAS # |
2283349-24-4
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| PubChem CID |
146623164
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| Appearance |
White to off-white solid powder
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| LogP |
2.3
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
33
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| Complexity |
714
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| Defined Atom Stereocenter Count |
1
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| SMILES |
CC1=C(C=C(C=C1OC)C2=NN3[C@@H](CCNC3=C2C(=O)N)C4CCN(CC4)C(=O)C=C)OC
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| InChi Key |
ZFDGMDVYMNWICG-KRWDZBQOSA-N
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| InChi Code |
InChI=1S/C24H31N5O4/c1-5-20(30)28-10-7-15(8-11-28)17-6-9-26-24-21(23(25)31)22(27-29(17)24)16-12-18(32-3)14(2)19(13-16)33-4/h5,12-13,15,17,26H,1,6-11H2,2-4H3,(H2,25,31)/t17-/m0/s1
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| Chemical Name |
(7S)-2-(3,5-dimethoxy-4-methylphenyl)-7-(1-prop-2-enoylpiperidin-4-yl)-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrimidine-3-carboxamide
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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 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.) |
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| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.2049 mL | 11.0246 mL | 22.0493 mL | |
| 5 mM | 0.4410 mL | 2.2049 mL | 4.4099 mL | |
| 10 mM | 0.2205 mL | 1.1025 mL | 2.2049 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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