| Size | Price | |
|---|---|---|
| 500mg | ||
| 1g | ||
| Other Sizes |
| Targets |
Multiple kinases such as RET, ABL1, ALK, AXL, and EGFR, with IC50 values ranging from 0.3 nM to 48 nM.
|
|---|---|
| ln Vitro |
Activity against various kinases: Int-3 demonstrated activity against a panel of kinases, including but not limited to RET, ABL1, ALK, AXL, and EGFR, with IC50 values ranging from 0.3 nM to 48 nM. [1]
Selectivity profile: Int-3 showed greater than 100-fold selectivity for RET over a broad panel of 468 kinases and mutant variants. [1] |
| ln Vivo |
Tumor growth inhibition: In RET-driven tumor xenograft models, Int-3 demonstrated robust and durable tumor growth inhibition with once-daily oral dosing. [1]
Pharmacodynamics: Int-3 treatment resulted in significant and sustained target inhibition, as measured by pRET levels in tumor tissues. [1] |
| Enzyme Assay |
Kinase inhibition assay: Int-3 was tested against a panel of kinases to determine its IC50 values, demonstrating potent and selective inhibition of RET and certain other kinases. [1]
|
| Cell Assay |
Anti-proliferative activity: Int-3 inhibited the proliferation of RET-dependent cancer cell lines with GI50 values in the low nanomolar range. [1]
Western blotting: Used to assess pRET levels and target engagement in tumor tissue samples and cell lines. [1] |
| Animal Protocol |
Tumor xenograft models: Int-3 was administered orally once daily to mice bearing RET-driven tumor xenografts. Tumor volume and body weight were monitored over time to assess efficacy and toxicity. [1]
Pharmacodynamics sampling: Tumor tissues were collected at various time points post-dosing to assess target inhibition by measuring pRET levels using western blotting. [1] |
| ADME/Pharmacokinetics |
Oral bioavailability: Int-3 demonstrated good oral bioavailability in preclinical species. [1]
PK profile: Int-3 exhibited a favorable pharmacokinetic profile, supporting once-daily oral dosing in vivo. [1] |
| Toxicity/Toxicokinetics |
Preclinical toxicity: Int-3 was well-tolerated in preclinical species, with no observed severe toxicity at efficacious doses. [1]
Maximum tolerated dose (MTD): Not specifically mentioned in the document for Int-3, but generally evaluated as part of preclinical toxicology studies. [1] |
| References | |
| Additional Infomation |
Background: Int-3 is a potent and selective RET inhibitor discovered through fragment-based drug design and structure-based drug design approaches. [1]
Indication: Int-3 is being developed for the treatment of RET-altered cancers, including thyroid cancers, lung cancers, and other solid tumors harboring RET fusions or mutations. [1] |
| Molecular Formula |
C18H30N4O2
|
|---|---|
| Molecular Weight |
334.46
|
| Exact Mass |
334.236876
|
| CAS # |
643087-19-8
|
| PubChem CID |
86659556
|
| Appearance |
Typically exists as solids at room temperature
|
| LogP |
2.2
|
| Hydrogen Bond Donor Count |
2
|
| Hydrogen Bond Acceptor Count |
5
|
| Rotatable Bond Count |
7
|
| Heavy Atom Count |
24
|
| Complexity |
381
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
CC(C)(C)OC(=O)NCCCN1CCN(CC1)C2=CC=C(C=C2)N
|
| InChi Key |
VIOMMXBDSUFFCI-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C18H30N4O2/c1-18(2,3)24-17(23)20-9-4-10-21-11-13-22(14-12-21)16-7-5-15(19)6-8-16/h5-8H,4,9-14,19H2,1-3H3,(H,20,23)
|
| Chemical Name |
tert-butyl N-[3-[4-(4-aminophenyl)piperazin-1-yl]propyl]carbamate
|
| Synonyms |
Aniline-piperazine-C3-NH-Boc; SCHEMBL24257354; VIOMMXBDSUFFCI-UHFFFAOYSA-N; HY-133702; tert-butyl {3-[4-(4-aminophenyl)-piperazin-1-yl]propyl}carbamate; tert-butyl{3-[4-(4-aminophenyl)-piperazin-1-yl]propyl}carbamate
|
| 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)
|
| 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
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 | 2.9899 mL | 14.9495 mL | 29.8989 mL | |
| 5 mM | 0.5980 mL | 2.9899 mL | 5.9798 mL | |
| 10 mM | 0.2990 mL | 1.4949 mL | 2.9899 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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