| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
|
||
| 10mg |
|
||
| 25mg |
|
||
| 50mg |
|
||
| 100mg |
|
||
| 250mg |
|
||
| 500mg |
|
||
| Other Sizes |
|
Purity: ≥98%
KRIBB11, a novel and potent inhibitor of Heat shock factor 1 (HSF1), abolishes the heat shock-induced luciferase activity with an IC50 of 1.2 μM. Heat shock protein 90 (Hsp90) is the master switch for heat shock protein (HSP) expression in eukaryotes and has an important role in many cancers. Biochemical inhibitors of Hsp90 are in advanced clinical development for the treatment of solid and hematological malignancies. As an inhibitor of the transcription factor Heat Shock Factor 1 (HSF1), KRIBB11 can inhibit cancer cell proliferation, arrests the cell cycle at G2/M phase and induces apoptosis. But it does not inhibit heat shock-induced recruitment of HSF1 to the hsp70 promoter or phosphorylation of HSF1 Ser-230. KRIBB11 inhibits heat shock-induced recruitment of pTEFb to the hsp70 promoter and p-TEFb-dependent Phosphorylation of polⅡ CTD Ser-2. Immunoblotting assays showed that the expression of HSP70 was lower in KRIBB11-treated tumor tissue than in control tissues. Because HSPs are expressed at high levels in a wide range of tumors, these results strengthen the rationale for targeting HSF1 in cancer therapy.
| ln Vitro |
KRIBB11 prevents downstream target proteins of HSF1, including HSP27 and HSP70, from being induced. In HCT-116 cells, KRIBB11 causes apoptosis and growth arrest. KRIBB11 prevents p-TEFb (positive transcription elongation factor b) from being recruited to the hsp70 promoter in an HSF1-dependent manner [1]. After KRIBB11 treatment, PARP and caspase-3 cleavage increased in the cells. KRIBB11 incubation on RKO results in an IC50 of 20–30 μM and a toxicity threshold of about 10 μM [2].
|
||
|---|---|---|---|
| ln Vivo |
In nude mice without weight loss, KRIBB11 (50 mg/kg, intraperitoneal injection) inhibited 47.4% of tumor growth [1].
|
||
| Animal Protocol |
|
||
| References |
|
||
| Additional Infomation |
KRIBB11 is a member of the class of indazoles that is 1H-indazole substituted by a [6-(methylamino)-3-nitropyridin-2-yl]amino group at position 5. It is an inhibitor of heat shock factor 1 (IC50 = 1.2muM) and suppresses tumour growth in mouse xenograft models. It has a role as an apoptosis inducer, an antineoplastic agent and a heat shock factor 1 inhibitor. It is a member of indazoles, an aromatic amine, an aminopyridine and a C-nitro compound.
|
| Molecular Formula |
C13H12N6O2
|
|
|---|---|---|
| Molecular Weight |
284.27
|
|
| Exact Mass |
284.102
|
|
| CAS # |
342639-96-7
|
|
| Related CAS # |
|
|
| PubChem CID |
69894253
|
|
| Appearance |
Yellow to orange solid powder
|
|
| Density |
1.5±0.1 g/cm3
|
|
| Boiling Point |
535.0±50.0 °C at 760 mmHg
|
|
| Flash Point |
277.3±30.1 °C
|
|
| Vapour Pressure |
0.0±1.4 mmHg at 25°C
|
|
| Index of Refraction |
1.812
|
|
| LogP |
4.3
|
|
| Hydrogen Bond Donor Count |
3
|
|
| Hydrogen Bond Acceptor Count |
6
|
|
| Rotatable Bond Count |
3
|
|
| Heavy Atom Count |
21
|
|
| Complexity |
376
|
|
| Defined Atom Stereocenter Count |
0
|
|
| InChi Key |
NDJJEQIMIJJCLL-UHFFFAOYSA-N
|
|
| InChi Code |
InChI=1S/C13H12N6O2/c1-14-12-5-4-11(19(20)21)13(17-12)16-9-2-3-10-8(6-9)7-15-18-10/h2-7H,1H3,(H,15,18)(H2,14,16,17)
|
|
| Chemical Name |
2-N-(1H-indazol-5-yl)-6-N-methyl-3-nitropyridine-2,6-diamine
|
|
| Synonyms |
|
|
| 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) |
|
|||
|---|---|---|---|---|
| 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 | 3.5178 mL | 17.5889 mL | 35.1778 mL | |
| 5 mM | 0.7036 mL | 3.5178 mL | 7.0356 mL | |
| 10 mM | 0.3518 mL | 1.7589 mL | 3.5178 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
COA
