| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
|
||
| 5mg |
|
||
| 10mg | |||
| Other Sizes |
| Targets |
IST5-002 targets the SH2 domain of signal transducer and activator of transcription 5 (STAT5), including both the Stat5a and Stat5b isoforms. By binding to this domain, it inhibits STAT5 phosphorylation and dimerization, which are essential steps for its activation and nuclear translocation. This blocks STAT5-mediated transcriptional activity and downstream signaling.
|
|---|---|
| ln Vitro |
The transcriptional activity of Stat5a and Stat5b is dose-dependently inhibited by IST5-002 (1.5-25 μM, 2 h) [1]. In K562 cells, Bcr-Abl-induced Stat5a/b phosphorylation is inhibited by IST5-002 (0-40 μM, 3 hours) [1]. IST5-002 (5-100 μM, 2 hours) prevents PC-3 cells from dimerizing and T47D cells from phosphorylate Stat5a/b [1]. IST5-002 (5-100 μM, 2 hours) prevents DNA binding of Stat5 target genes and PC-3 cells, as well as Stat5 nuclear translocation [1]. In CWR22Rv1 and LNCaP cells, IST5-002 (2-50 μM, 48 hours) decreases the expression of Stat5a/b target genes (Bcl-xL and cyclin D1) [1]. IST5-002 (3.1-50 μM, 72 hours) stops the development of human prostate cancer cells by causing them to undergo apoptosis [1]. In organ explant cultures containing patient-derived prostate cancer, IST5-002 (25-100 μM, 7 days) causes epithelial cell death [1]. IST5-002 (5 μM, 24-72h) causes death in CML cells that are both imatinib-sensitive and -resistant by inhibiting the phosphorylation of Stat5a/b [1].
In vitro, IST5-002 inhibits the transcriptional activity of Stat5a and Stat5b with IC50 values of 1.5 μM and 3.5 μM, respectively, in PC-3 cells. It blocks Bcr-Abl-induced Stat5a/b phosphorylation at 5 μM in Bcr-Abl-positive K562 cells. It shows no specific inhibition of other kinases in a panel of 50 kinases and does not block transcriptional activity of Stat3, demonstrating its selectivity. |
| ln Vivo |
The RORγt inverse agonist 29 (ip, 25-100 mg/kg daily for 10 days) suppresses tumor growth in prostate cancer xenograft models [1].
In vivo, IST5-002 induces apoptosis and death in prostate cancer cells and chronic myeloid leukemia (CML) cells. It suppresses Stat5a/b-mediated growth of prostate cancer through induction of apoptosis in experimental models in vitro, in vivo, and ex vivo. |
| Enzyme Assay |
STAT5 SH2 domain binding is assessed using biochemical assays such as surface plasmon resonance or fluorescence polarization. The interaction between IST5-002 and the recombinant STAT5 SH2 domain is measured to determine the binding affinity.
|
| Cell Assay |
Cell Viability Assay [1]
Cell Types: CWR22Rv1, LNCaP and DU145 Cell Tested Concentrations: 3.1, 6.3, 12.5, 25, 50 μM Incubation Duration: 72 hrs (hours) Experimental Results: 50% to 80% reduction in viable cells at 12.5 μM. Cell cycle analysis [1] Cell Types: LNCaP and CWR22Rv1 Cell Tested Concentrations: 6, 12, 25 μM Incubation Duration: 72 hrs (hours) Experimental Results: Increased proportion of dead cells (sub-G1), diminished proportion of viable cells (G2–M)). Western Blot Analysis[1] Cell Types: Bcr-Abl positive K562 cells Tested Concentrations: 0, 1, 5, 10, 20, 40 μM Incubation Duration: 3 hrs (hours) Experimental Results: Inhibition of Bcr-Abl-induced Stat5a/b phosphorylation at 5 μM , does not affect the tyrosine phosphorylation level of Bcr-Abl. Immunofluorescence [1] Cell Types: PC-3 Cell Tested Concentrations: 5, 10, 15, 20, 40 μM Incubation Duration: 2 hrs (hours) Experimental Results: Inhibition of Prl (prolactin)-induced Stat5 nuclear translocation. STAT5 phosphorylation and transcriptional activity are assessed in prostate cancer cell lines (e.g., PC-3, CWR22Rv1) and CML cells (e.g., K562). Cells are treated with IST5-002, and STAT5 phosphorylation is measured by Western blot. Transcriptional activity is assessed using reporter gene assays. |
| Animal Protocol |
Animal/Disease Models: Prostate cancer (CWR22Rv1) xenograft model [1] Doses: 25, 50 and 100 mg/kg
Route of Administration: intraperitoneal (ip) injection, one time/day for 10 days Experimental Results: Induced massive loss of viable tumor cells and dead round cells accumulation. Induction of cell death by apoptosis (shown by DNA fragments in tumor sections). At 25, 50 and 100 mg/kg, nuclear Stat5a/b content diminished by 60%, 78% and 90%, respectively. In vivo efficacy is evaluated in mouse xenograft models of prostate cancer and CML. IST5-002 is administered systemically, and tumor volume is measured over time. Tumor growth inhibition and markers of apoptosis and STAT5 signaling are assessed. |
| ADME/Pharmacokinetics |
As a small molecule, IST5-002 is expected to have favorable drug-like properties. It is soluble in DMSO at 10 mM. Its pharmacokinetic profile is consistent with a small molecule inhibitor targeting intracellular proteins.
|
| Toxicity/Toxicokinetics |
As a STAT5 inhibitor, potential toxicities may include effects on normal hematopoiesis, as STAT5 is involved in the development and function of various immune cells. However, its selectivity for STAT5 over other STAT family members may reduce off-target effects.
|
| References | |
| Additional Infomation |
IST5-002 is a research compound used to study the role of STAT5 in cancer and to validate STAT5 as a therapeutic target. It induces apoptosis in prostate cancer cells and CML cells, making it a promising candidate for the treatment of these malignancies. It is suitable for research applications focused on understanding the role of Stat5 in cancer progression and therapeutic targeting.
|
| Molecular Formula |
C17H20N5O7P
|
|---|---|
| Molecular Weight |
435.32792
|
| Exact Mass |
437.11
|
| CAS # |
13484-66-7
|
| Related CAS # |
57828-96-3;174063-89-9 (sodium);13484-66-7 (free acid);
|
| PubChem CID |
59310
|
| Appearance |
White to off-white solid powder
|
| Density |
1.81g/cm3
|
| Boiling Point |
798.5ºC at 760mmHg
|
| Flash Point |
436.7ºC
|
| Vapour Pressure |
6.67E-27mmHg at 25°C
|
| LogP |
0.239
|
| Hydrogen Bond Donor Count |
5
|
| Hydrogen Bond Acceptor Count |
11
|
| Rotatable Bond Count |
7
|
| Heavy Atom Count |
30
|
| Complexity |
621
|
| Defined Atom Stereocenter Count |
4
|
| SMILES |
C1=CC=C(C=C1)CNC2=C3C(=NC=N2)N(C=N3)[C@H]4[C@@H]([C@@H]([C@H](O4)COP(=O)(O)O)O)O
|
| InChi Key |
DWVANBHPEPSMOV-LSCFUAHRSA-N
|
| InChi Code |
InChI=1S/C17H20N5O7P/c23-13-11(7-28-30(25,26)27)29-17(14(13)24)22-9-21-12-15(19-8-20-16(12)22)18-6-10-4-2-1-3-5-10/h1-5,8-9,11,13-14,17,23-24H,6-7H2,(H,18,19,20)(H2,25,26,27)/t11-,13-,14-,17-/m1/s1
|
| Chemical Name |
[(2R,3S,4R,5R)-5-[6-(benzylamino)purin-9-yl]-3,4-dihydroxyoxolan-2-yl]methyl dihydrogen phosphate
|
| 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) |
H2O : ~125 mg/mL (~285.82 mM)
DMSO : ~125 mg/mL (~285.82 mM) |
|---|---|
| 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 | 2.2971 mL | 11.4855 mL | 22.9711 mL | |
| 5 mM | 0.4594 mL | 2.2971 mL | 4.5942 mL | |
| 10 mM | 0.2297 mL | 1.1486 mL | 2.2971 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.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
