| Size | Price | |
|---|---|---|
| 500mg | ||
| 1g | ||
| Other Sizes |
Bomedemstat (IMG7289) is a novel, potent and orally bioavailable inhibitor of lysine-specific demethylase 1 (LSD1 or KDM1A) with anticancer activity. LSD1 is an enzyme shown to be vital in cancer stem/progenitor cells, particularly neoplastic bone marrow cells. In non-clinical studies, bomedemstat demonstrated robust in vivo anti-tumor efficacy across a range of myeloid malignancies as a single agent and in combination with other chemotherapeutic agents. Bomedemstat is an investigational agent currently being evaluated in ongoing clinical trials (ClinicalTrials.gov Identifier: NCT03136185, NCT04262141 and NCT04081220). Bomedemstat has FDA Orphan Drug and Fast Track Designation for the treatment of myelofibrosis and essential thrombocythemia, Orphan Drug Designation for treatment of acute myeloid leukemia and PRIME designation by the European Medicines Agency for the treatment of MF.
| Targets |
LSD1/lysine-specific demethylase 1
|
|---|---|
| ln Vitro |
Bomedemstat increases p53 expression and methylation while concurrently inhibiting proliferation and inducing apoptosis in Jak2V617F cells[1]. Cell cycle arrest and enhanced survival are caused by bomedemstat (50 nM-1 μM; 96 h), which also promotes apoptosis via BCL-XL and PUMA in a TP53-dependent manner[1].
|
| ln Vivo |
Treatment with bomedemstat (oral gavage; 45 mg/kg; once daily; 56 d) improves or returns blood cell counts to normal, decreases spleen sizes, reestablishes normal splenic architecture, and lessens fibrosis in the bone marrow[1].
|
| Cell Assay |
Apoptosis Analysis[1]
Cell Types: SET-2 cells Tested Concentrations: 50 nM, 100 nM, and 1 μM Incubation Duration: 96 hrs (hours) Experimental Results: diminished levels of the antiapoptotic protein BCL-XL and increased levels of the pro-apoptotic protein PUMA. |
| Animal Protocol |
Animal/Disease Models: Mx-Jak2V617F mice[1]
Doses: 45 mg/kg Route of Administration: po (oral gavage); 45 mg/kg; one time/day; 56 days Experimental Results: decreased splenomegaly Dramatically with a few treated mice normalizing their spleen weight, the 56-day course led to partial restoration of lymph follicles and spleen architecture by histological examination. |
| References | |
| Additional Infomation |
IMG-7289 is under investigation in clinical trial NCT03136185 (IMG-7289 in Patients With Myelofibrosis).
Bomedemstat is an orally available, irreversible inhibitor of lysine-specific demethylase 1 (LSD1), with potential antineoplastic activity. Upon administration, bomedemstat binds to and inhibits LSD1, a demethylase that suppresses the expression of target genes by converting the di- and mono-methylated forms of lysine at position 4 of histone H3 (H3K4) to mono- and unmethylated H3K4. LSD1 inhibition enhances H3K4 methylation and increases the expression of tumor suppressor genes. In addition, LSD1 demethylates mono- or di-methylated H3K9 which increases gene expression of tumor promoting genes; thus, inhibition of LSD1 also promotes H3K9 methylation and decreases transcription of these genes. Altogether, this may lead to an inhibition of cell growth in LSD1-overexpressing tumor cells. LSD1, an enzyme belonging to the flavin adenine dinucleotide (FAD)-dependent amine oxidase family is overexpressed in certain tumor cells and plays a key role in the regulation of gene expression, tumor cell growth and survival. |
| Molecular Formula |
C28H34FN7O2
|
|---|---|
| Molecular Weight |
519.61366891861
|
| Exact Mass |
519.275
|
| Elemental Analysis |
C, 64.72; H, 6.60; F, 3.66; N, 18.87; O, 6.16
|
| CAS # |
1990504-34-1
|
| Related CAS # |
Bomedemstat ditosylate;1990504-72-7;Bomedemstat hydrochloride;Bomedemstat dihydrochloride; 1990504-34-1
|
| PubChem CID |
122460381
|
| Appearance |
Colorless to light yellow Ointment
|
| LogP |
2.3
|
| Hydrogen Bond Donor Count |
2
|
| Hydrogen Bond Acceptor Count |
7
|
| Rotatable Bond Count |
10
|
| Heavy Atom Count |
38
|
| Complexity |
779
|
| Defined Atom Stereocenter Count |
3
|
| SMILES |
CN1CCN(CC1)C(=O)[C@H](CCCN[C@@H]2C[C@H]2C3=CC=C(C=C3)F)NC(=O)C4=CC=C(C=C4)N5C=CN=N5
|
| InChi Key |
KQKBMHGOHXOHTD-KKUQBAQOSA-N
|
| InChi Code |
InChI=1S/C28H34FN7O2/c1-34-15-17-35(18-16-34)28(38)25(3-2-12-30-26-19-24(26)20-4-8-22(29)9-5-20)32-27(37)21-6-10-23(11-7-21)36-14-13-31-33-36/h4-11,13-14,24-26,30H,2-3,12,15-19H2,1H3,(H,32,37)/t24-,25-,26+/m0/s1
|
| Chemical Name |
N-[(2S)-5-{[(1R,2S)-2-(4-fluorophenyl)cyclopropyl]amino}-1-(4-methylpiperazin-1-yl)-1-oxopentan-2-yl]-4-(1H-1,2,3-triazol-1-yl)benzamide
|
| Synonyms |
IMG7289; Bomedemstat, IMG-7289; Bomedemstat; 1990504-34-1; IMG-7289; Bomedemstat [USAN]; Y2T4ALDEAT; BOMEDEMSTAT (IMG-7289); UNII-Y2T4ALDEAT; WHO 11114; IMG 7289
|
| 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 : ~100 mg/mL (~192.45 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 | 1.9245 mL | 9.6226 mL | 19.2452 mL | |
| 5 mM | 0.3849 mL | 1.9245 mL | 3.8490 mL | |
| 10 mM | 0.1925 mL | 0.9623 mL | 1.9245 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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