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| Targets |
Integrin α2β1 (specifically the α2I domain). BTT-3033 is a selective inhibitor of α2β1 integrin that binds to the α2I domain. It inhibits platelet aggregation to collagen I and cell proliferation. The compound exhibits selectivity for α2β1 over integrins α3β1, α4β1, α5β1, and αv.
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| ln Vitro |
BTT-3033 (1 nM-100 μM, 2 hours) is more selective for α2β1 than α3β1, α4β1, α5β1, and αv, and it reduces the adherence of CHO-α2wt cells to rat tail collagen I (EC50: 130 nM)[1]. With an EC50 value of 6 μM in mouse whole blood, BTT-3033 (10 μM, 5 minutes) inhibits human platelet binding to type I collagen-coated capillaries under flow [1]. Under shear stress conditions, CHO cells expressing α2 are unable to bind to type I collagen when exposed to BTT-3033 (10 μM) for five minutes [1]. Human prostate smooth muscle contractions generated by thromboxane A2 and neurogenic stimuli are inhibited by BTT-3033 (1 μM, 60 min) [3]. BTT-3033 (25 and 50 μM, 48 hours) causes G1 cell cycle arrest in LNcap-FGC and DU-145 cells, which decreases cell survival and proliferation [4]. Using a combination of caspase-3 activation, ΔΨm depletion, Bax protein overexpression, and ROS activation, BTT-3033 (50 μM) causes apoptosis in 48 hours [4]. In human articular cartilage-derived chondrocytes, BTT-3033 (10 μM, 15/28 days) promotes the expression of MMP1 and MT-MMP1 and suppresses the production of MMP13 [5].
BTT-3033 inhibits α2β1 integrin binding to collagen I with an EC50 of 130 nM. It binds to the α2I domain and inhibits platelet aggregation to collagen I-coated capillaries under flow. The compound also inhibits binding of α2-expressing CHO cells to collagen I under shear stress conditions. BTT-3033 inhibits cell proliferation and induces apoptosis. It has been investigated for potential applications in cancer research, particularly prostate cancer. |
| ln Vivo |
In a mouse air sac model, BTT-3033 (orally, 10 mg/kg, 24 and 2 hours before PAF induction) demonstrated anti-inflammatory effects [2]. In an arachidonic acid-induced ear edema model, BTT-3033 (orally, 10 mg/kg, 48, 24 and 2 hours before ear swelling) demonstrated anti-inflammatory effects [2].
In vivo, BTT-3033 has been studied for its potential therapeutic applications, particularly in prostate cancer. As an orally active α2β1 integrin inhibitor, it inhibits platelet binding to collagen I and cell proliferation, and induces apoptosis. The compound's ability to inhibit integrin-mediated cell adhesion and signaling makes it a promising candidate for further in vivo studies in cancer and other diseases. |
| Enzyme Assay |
In vitro receptor binding assays for BTT-3033 involve measuring its affinity for integrin α2β1 using binding assays with collagen I. The compound is incubated with α2β1 integrin or α2-expressing cells in the presence of labeled collagen I. Bound and free ligand are separated, and binding affinity is measured. EC50 values (130 nM) are determined from concentration-response curves.
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| Cell Assay |
Cell Viability Assay [4]
Cell Types: LNcap-FGC and DU-145 Cell Tested Concentrations: 0.05, 0.5, 5, 25 and 50 μM Incubation Duration: 48 hrs (hours) Experimental Results: diminished cell viability at 25 μM and 50 μM. Cell viability assay [4] Cell Types: LNcap-FGC and DU-145 Cell Tested Concentrations: 5, 25 and 50 μM Incubation Duration: 48 hrs (hours) Experimental Results: Induced apoptosis by approximately 20%, 32% and 47% (LNcap-FGC) and 26%, 41%, and 59% at 5, 25, and 50 μM (DU-145). Western Blot Analysis [4] Cell Types: LNcap-FGC and DU-145 Cell Tested Concentrations: 25 μM Incubation Duration: 48 hrs (hours) Experimental Results: Result in downregulation of N-cadherin and upregulation of E-cadherin (EMT related protein). In vitro cellular assays for BTT-3033 involve treating cells expressing integrin α2β1 with the compound and measuring cell adhesion, proliferation, or apoptosis. Cells are treated with various concentrations of BTT-3033, and adhesion to collagen I-coated surfaces is assessed. Cell proliferation is measured by metabolic assays, and apoptosis is evaluated by flow cytometry or caspase activity assays. |
| Animal Protocol |
Animal/Disease Models: PAF (platelet activating factor)-induced mouse air sac model [2]
Doses: 24 hrs (hrs (hours)) and 2 hrs (hrs (hours)) before PAF induction 1, 10 mg/kg Route of Administration: Oral Experimental Results:Leukocyte infiltration diminished by approximately 50% 10 mg/kg kilogram. Animal/Disease Models: Male DBA/1 mice (pharmacokinetic/PK/PK determination) [2] Doses: Single dose 10 mg/kg Route of Administration: Oral Experimental Results: Plasma level: Approximately 1 ng/mL 24 hrs (hrs (hours)) after administration. In vivo animal studies for BTT-3033 typically involve administration to mouse models of cancer or other diseases. The compound is orally administered, and efficacy is assessed by measuring tumor growth inhibition, metastasis, or survival. The compound's ability to inhibit integrin α2β1-mediated cell adhesion and signaling is evaluated in these models. |
| ADME/Pharmacokinetics |
Pharmacokinetic data for BTT-3033 shows that the compound is orally active. It has a molecular weight of 465.5 and a molecular formula of C23H20FN5O3S. The compound is soluble in DMSO. Further pharmacokinetic studies are needed to fully characterize its absorption, distribution, metabolism, and elimination profile.
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| Toxicity/Toxicokinetics |
Preclinical toxicity studies of BTT-3033 are limited. The compound is a potent and selective inhibitor of integrin α2β1 that has been investigated for its potential therapeutic applications. Comprehensive toxicological evaluation is needed before clinical development. The compound's selectivity for α2β1 over other integrins may contribute to a favorable safety profile.
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| References |
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| Additional Infomation |
BTT-3033 is an orally active, conformation-selective inhibitor of integrin α2β1 with an EC50 of 130 nM. It binds to the α2I domain and exhibits selectivity for α2β1 over integrins α3β1, α4β1, α5β1, and αv. BTT-3033 inhibits platelet aggregation to collagen I, inhibits cell proliferation, and induces apoptosis. The compound has been investigated for potential applications in cancer research, particularly prostate cancer.
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| Molecular Formula |
C23H20FN5O3S
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| Molecular Weight |
465.5034
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| Exact Mass |
465.127
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| Elemental Analysis |
C, 59.35; H, 4.33; F, 4.08; N, 15.05; O, 10.31; S, 6.89
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| CAS # |
1259028-99-3
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| PubChem CID |
49841251
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| Appearance |
White to off-white solid powder
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| Density |
1.4±0.1 g/cm3
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| Index of Refraction |
1.652
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| LogP |
2.97
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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 |
742
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| Defined Atom Stereocenter Count |
0
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| SMILES |
S(C1C=NN(C2C=CC(=CC=2)F)C=1)(N(C)C1C=CC(=CC=1)NC(NC1C=CC=CC=1)=O)(=O)=O
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| InChi Key |
NSLIQOPYDUKWTA-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C23H20FN5O3S/c1-28(33(31,32)22-15-25-29(16-22)21-11-7-17(24)8-12-21)20-13-9-19(10-14-20)27-23(30)26-18-5-3-2-4-6-18/h2-16H,1H3,(H2,26,27,30)
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| Chemical Name |
1-[4-[[1-(4-fluorophenyl)pyrazol-4-yl]sulfonyl-methylamino]phenyl]-3-phenylurea
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| Synonyms |
BTT3033; BTT 3033; BTT-3033
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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 : ~250 mg/mL (~537.06 mM)
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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 | 2.1482 mL | 10.7411 mL | 21.4823 mL | |
| 5 mM | 0.4296 mL | 2.1482 mL | 4.2965 mL | |
| 10 mM | 0.2148 mL | 1.0741 mL | 2.1482 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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