| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
|
||
| 5mg |
|
||
| Other Sizes |
| Targets |
DOT1L
DOT1L (Disruptor of telomeric silencing-1-like); histone methyltransferase responsible for catalyzing mono-, di-, and tri-methylation of histone H3 at lysine 79 (H3K79). |
|---|---|
| ln Vitro |
Dot1L-IN-1 (analog 7) TFA efficiently suppresses the growth of the human MLL-rearranged leukemia cell line MV4-11, which carries the oncogenic MLL-AF4 fusion (IC50=5 nM)[1].
Dot1L-IN-1 TFA exhibits DOT1L inhibition with Ki = 2 pM and IC50 <0.1 nM; potently suppresses H3K79 dimethylation in HeLa cells (IC50=3 nM) and HoxA9 promoter activity in Molm-13 MLL-rearranged cells (IC50=17 nM); suppresses growth of MV4-11 cells (IC50=5 nM). |
| ln Vivo |
No in vivo activity data reported for this specific inhibitor; DOT1L inhibitors suppress MLL-rearranged leukemia growth in mouse xenograft models; this compound is expected to have similar efficacy.
|
| Enzyme Assay |
Enzymatic activity: purified DOT1L enzyme is incubated with 3H-labeled S-adenosylmethionine and H3K79 peptide substrate in the presence of Dot1L-IN-1 (0.1 pM-10 nM); methyltransferase activity measured by scintillation counting.
|
| Cell Assay |
HeLa cells (to assess global H3K79 methylation) or MLL-rearranged leukemia cells (Molm-13, MV4-11) are treated with Dot1L-IN-1 TFA (0.1-1000 nM) for 72 h; H3K79 methylation assessed by Western blot; cell viability measured by MTS or CellTiter-Glo.
|
| Animal Protocol |
No in vivo protocol defined; standard DOT1L inhibitor efficacy study in MLL-rearranged leukemia xenografts: mice receive Dot1L-IN-1 (0.5-5 mg/kg, IP or PO, daily for 21-28 days); tumor volume and H3K79me2 levels are measured.
|
| ADME/Pharmacokinetics |
No PK data available for this specific compound; as a small molecule DOT1L inhibitor, likely orally bioavailable; detailed PK parameters would require dedicated studies.
|
| Toxicity/Toxicokinetics |
No toxicity data available; as a histone methyltransferase inhibitor, potential on-target effects include alterations in gene expression programs; standard toxicology evaluation would be required.
|
| References | |
| Additional Infomation |
Dot1L-IN-1 TFA is a research tool for epigenetics; not approved for clinical use; no clinical trial status; for research use only in cancer epigenetics.
|
| Molecular Formula |
C34H37CLF3N9O4S
|
|---|---|
| Molecular Weight |
760.23
|
| Related CAS # |
Dot1L-IN-1;2088518-50-5
|
| Appearance |
Off-white to light yellow solid powder
|
| 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) |
DMSO :~50 mg/mL (~65.77 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 | 1.3154 mL | 6.5770 mL | 13.1539 mL | |
| 5 mM | 0.2631 mL | 1.3154 mL | 2.6308 mL | |
| 10 mM | 0.1315 mL | 0.6577 mL | 1.3154 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
