| Size | Price | Stock | Qty |
|---|---|---|---|
| 50mg |
|
||
| 100mg |
|
||
| 500mg | |||
| 1g | |||
| Other Sizes |
| Targets |
The primary target of CWI1-2 hydrochloride is IGF2BP2, an m6A reader protein that recognizes and binds to N6-methyladenosine (m6A)-modified mRNAs. IGF2BP2 promotes the stability and translation of its target mRNAs, which include oncogenes involved in cancer cell proliferation and survival. By binding to IGF2BP2 and inhibiting its interaction with m6A-modified target transcripts, CWI1-2 hydrochloride reduces the expression of these oncogenes, inducing apoptosis and differentiation. The compound shows promising anti-leukemic effects.
|
|---|---|
| ln Vitro |
CWI1-2 hydrochloride (0–1 μM, 24 h) exhibits good anti-leukemia activity [1].
In vitro studies demonstrate that CWI1-2 hydrochloride binds IGF2BP2 and inhibits its interaction with m6A-modified target transcripts. The compound induces apoptosis and differentiation and shows promising anti-leukemic effects. CWI1-2 hydrochloride is an effective IGF2BP2 inhibitor. No detailed IC50 or EC50 values have been published in the available literature. |
| ln Vivo |
In BMT receptor B6.SJL (CD45.1) mice, CWI1-2 (5 mg/kg, iv, once daily, 7–10 days) hydrochloride can dramatically postpone the onset and survival time of leukemia without having a noticeable effect on body weight [1].
In vivo, CWI1-2 (5 mg/kg, i.v., once daily, 7-10 days) significantly delays the onset of leukemia and prolongs survival time in BMT recipient B6.SJL (CD45.1) mice without significant effects on body weight. These results demonstrate the in vivo efficacy of CWI1-2 hydrochloride in a leukemia model. The compound's ability to inhibit IGF2BP2 and induce apoptosis and differentiation contributes to its anti-leukemic activity. |
| Enzyme Assay |
The IGF2BP2 binding activity of CWI1-2 hydrochloride can be assessed using in vitro binding assays. In a typical assay, recombinant IGF2BP2 protein is incubated with m6A-modified RNA probes and varying concentrations of CWI1-2 hydrochloride. The disruption of the IGF2BP2-RNA interaction is measured using fluorescence polarization, surface plasmon resonance, or RNA pull-down assays. The compound's ability to inhibit IGF2BP2 binding to m6A-modified transcripts is assessed.
|
| Cell Assay |
Apoptosis Analysis[1]
Cell Types: MonoMac6, MOLM13 Tested Concentrations: 0-1 μM Incubation Duration: 24 h Experimental Results: Induced significant cell differentiation and apoptosis in a concentration-dependent manner in IGF2BP2-high cells but not in IGF2BP2-low cells. decreased Gln uptake and impaired mitochondrial function, resulting in decreased ATP production in AML cells. Dramatically inhibited the colony-forming ability of MA9- induced leukemic mouse blasts and greatly impairs the self-renewal of LSC/LIC. The cellular activity of CWI1-2 hydrochloride is assessed using leukemia cell lines. Cells are treated with varying concentrations of CWI1-2 hydrochloride. IGF2BP2 target gene expression is measured by qPCR or Western blotting. Apoptosis is assessed by annexin V/propidium iodide staining or caspase activation assays. Differentiation is assessed by measuring cell surface markers or morphological changes. Cell viability is measured using MTT or CellTiter-Glo assays. |
| Animal Protocol |
CWI1-2 hydrochloride has been evaluated in a mouse model of leukemia. In these studies, the compound is administered intravenously at 5 mg/kg once daily for 7-10 days. The onset of leukemia and survival time are monitored. The compound significantly delays the onset of leukemia and prolongs survival time without significant effects on body weight. These results demonstrate the in vivo efficacy of CWI1-2 hydrochloride.
|
| ADME/Pharmacokinetics |
No detailed pharmacokinetic data has been published for CWI1-2 hydrochloride. The compound has a molecular weight of 556.23 and a molecular formula of C22H18Cl4N6O3. It is soluble in DMSO at 125 mg/mL (224.73 mM). The compound is typically stored at 4°C, sealed and protected from moisture. Further studies would be needed to characterize its absorption, distribution, metabolism, and excretion properties.
|
| Toxicity/Toxicokinetics |
No detailed toxicity data has been published for CWI1-2 hydrochloride. In the mouse leukemia model, the compound did not cause significant effects on body weight at the tested dose of 5 mg/kg. As an IGF2BP2 inhibitor, the compound may have on-target effects on m6A-mediated gene regulation in normal cells. Comprehensive toxicology studies would be required to evaluate its safety profile for potential therapeutic development.
|
| References |
[1]. Hengyou Weng, et al. The m6A reader IGF2BP2 regulates glutamine metabolism and represents a therapeutic target in acute myeloid leukemia. Cancer Cell. 2022 Dec 12;40(12):1566-1582.e10.
|
| Additional Infomation |
CWI1-2 hydrochloride (CAS# 2408590-37-2) is an inhibitor of IGF2BP2 that binds IGF2BP2 and inhibits its interaction with m6A-modified target transcripts. The compound induces apoptosis and differentiation and shows promising anti-leukemic effects. In vivo, CWI1-2 (5 mg/kg, i.v., once daily, 7-10 days) significantly delays leukemia onset and prolongs survival in mice. The molecular formula is C22H18Cl4N6O3 and molecular weight is 556.23.
|
| Molecular Formula |
C22H18CL4N6O3
|
|---|---|
| Molecular Weight |
556.228720188141
|
| Exact Mass |
554.02
|
| Elemental Analysis |
C, 47.51; H, 3.26; Cl, 25.49; N, 15.11; O, 8.63
|
| CAS # |
2408590-37-2
|
| Related CAS # |
CWI1-2;2408590-36-1
|
| PubChem CID |
168265662
|
| Appearance |
Light yellow to yellow solid powder
|
| Hydrogen Bond Donor Count |
6
|
| Hydrogen Bond Acceptor Count |
7
|
| Rotatable Bond Count |
8
|
| Heavy Atom Count |
35
|
| Complexity |
715
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
C1=CC(=C(C=C1Cl)/C=N/NC(=N/N=C/C2=C(C=CC(=C2)Cl)O)N/N=C\C3=C(C=CC(=C3)Cl)O)O.Cl
|
| InChi Key |
UXAOLDYLYMMMRC-FZQKVMMRSA-N
|
| InChi Code |
InChI=1S/C22H17Cl3N6O3.ClH/c23-16-1-4-19(32)13(7-16)10-26-29-22(30-27-11-14-8-17(24)2-5-20(14)33)31-28-12-15-9-18(25)3-6-21(15)34;/h1-12,32-34H,(H2,29,30,31);1H/b26-10-,27-11+,28-12+;
|
| Chemical Name |
(E)-N',N''-bis((E)-5-chloro-2-hydroxybenzylidene)-2-((Z)-5-chloro-2-hydroxybenzylidene)hydrazine-1-carbohydrazonhydrazide hydrochloride
|
| Synonyms |
CWI1-2 hydrochloride; CWI1-2 HCl; CWI1-2; CWI1 2 hydrochloride; CWI12 HCl
|
| 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 | 1.7978 mL | 8.9891 mL | 17.9782 mL | |
| 5 mM | 0.3596 mL | 1.7978 mL | 3.5956 mL | |
| 10 mM | 0.1798 mL | 0.8989 mL | 1.7978 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
