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| 1mg |
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| 5mg |
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| Targets |
The primary target of CWI1-2 is IGF2BP2, an m6A reader protein that recognizes and binds to N6-methyladenosine (m6A)-modified mRNAs. IGF2BP2 promotes AML development and self-renewal of leukemia stem/initiation cells by regulating expression of critical targets (e.g., MYC, GPT2, and SLC1A5) in the glutamine metabolism pathways in an m6A-dependent manner. By inhibiting IGF2BP2, CWI1-2 reduces the expression of these oncogenes, inducing apoptosis and differentiation.
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| ln Vitro |
CWI1-2 (0-1 μM, 24 h) exhibits good anti-leukemia efficacy [1].
In vitro studies demonstrate that CWI1-2 is an effective IGF2BP2 inhibitor that binds IGF2BP2 and inhibits its interaction with m6A-modified target transcripts. The compound induces apoptosis and differentiation and possesses anti-leukemic activity. CWI1-2 shows promising anti-leukemia effects in vitro. 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) can greatly postpone the onset and survival duration of leukemia without having a significant effect on body weight [1].
In vivo, CWI1-2 (5 mg/kg, i.v., once daily) 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 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 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. 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.
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| 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 is assessed using leukemia cell lines. Cells are treated with varying concentrations of CWI1-2. IGF2BP2 target gene expression (MYC, GPT2, SLC1A5) 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 has been evaluated in a mouse model of leukemia. In these studies, the compound is administered intravenously at 5 mg/kg once daily. 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.
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| ADME/Pharmacokinetics |
No detailed pharmacokinetic data has been published for CWI1-2. The compound has a molecular weight of 519.77 and a molecular formula of C22H17Cl3N6O3. It has a purity of ≥98%. Further studies would be needed to characterize its absorption, distribution, metabolism, and excretion properties, including oral bioavailability, plasma protein binding, clearance, and half-life.
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| Toxicity/Toxicokinetics |
Effects During Pregnancy and Lactation
◉ Overview of Use During Lactation There is currently no information regarding the clinical use of boratuzumab and vitolamine during lactation. Because boratuzumab is a large protein molecule with a molecular weight of approximately 150,000 Da, its concentration in breast milk is likely to be very low. Furthermore, it is likely to be partially destroyed in the infant's gastrointestinal tract, so the amount absorbed by the infant may be minimal. Vidoramine (monomethylaurestatin E) is a small molecule anticancer drug that may enter breast milk and be absorbed by the infant. Due to the potential for serious adverse reactions in breastfed infants, the manufacturer recommends discontinuing breastfeeding during boratuzumab treatment and for two months after the last dose. ◉ Effects on Breastfed Infants No published information found as of the revision date. ◉ Effects on Lactation and Breast Milk No published information found as of the revision date. No detailed toxicity data has been published for CWI1-2. 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 | |
| Additional Infomation |
See also: Polatuzumab Vedotin (note moved to).
CWI1-2 (CAS# 2408590-36-1) is an IGF2BP2 inhibitor that binds IGF2BP2 and inhibits its interaction with m6A-modified target transcripts. The compound induces apoptosis and differentiation and possesses anti-leukemic activity. In vivo, CWI1-2 (5 mg/kg, i.v., once daily) significantly delays leukemia onset and prolongs survival in mice. The molecular formula is C22H17Cl3N6O3 and molecular weight is 519.77. CWI1-2 is a research tool for studying IGF2BP2 and m6A-mediated gene regulation in leukemia. |
| Molecular Formula |
C22H17CL3N6O3
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| Molecular Weight |
519.77
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| Exact Mass |
518.042
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| CAS # |
2408590-36-1
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| Related CAS # |
CWI1-2 hydrochloride;2408590-37-2
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| PubChem CID |
155905758
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| Appearance |
Light yellow to yellow solid powder
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| LogP |
5.4
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| Hydrogen Bond Donor Count |
5
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
8
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| Heavy Atom Count |
34
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| Complexity |
715
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| Defined Atom Stereocenter Count |
0
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| 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
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| InChi Key |
ZNYMTTHEJHXHNS-FGORHZQOSA-N
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| InChi Code |
InChI=1S/C22H17Cl3N6O3/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)/b26-10-,27-11+,28-12+
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| Chemical Name |
1-[(Z)-(5-chloro-2-hydroxyphenyl)methylideneamino]-2,3-bis[(E)-(5-chloro-2-hydroxyphenyl)methylideneamino]guanidine
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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 : 100 mg/mL (192.39 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: 1.25 mg/mL (2.40 mM) in 10% DMSO + 40% PEG300 +5% Tween-80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution; with sonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 12.5 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 + to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.9239 mL | 9.6196 mL | 19.2393 mL | |
| 5 mM | 0.3848 mL | 1.9239 mL | 3.8479 mL | |
| 10 mM | 0.1924 mL | 0.9620 mL | 1.9239 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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