| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 25mg |
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IMT1B (LDC-203974; IMT-1B) is a novel first-in-class and allosteric inhibitor of mitochondrial RNA polymerase (POLRMT) with the potential for the treatment of cancer. POLRMT is a human mitochondrial RNA polymerase (POLRMT) and is essential for mtDNA transcription as well as biogenesis of the oxidative phosphorylation (OXPHOS) system.
| ln Vitro |
IMT1B is a non-competitive formulation that depletes substrate binding and remodeling in vitro by causing conformational changes in POLRMT [1]. In A2780, A549, and HeLa cells, IMT1B (0.01 nM–10 μM; 72–168 hours) dose-reduced cell viability [1]. IMT1B depletes cells even more [1]. The AMP/ATP proportion and the levels of phosphorylated AMPK are produced by IMT1B's elevation of mono- and di-phosphorylation.
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| ln Vivo |
IMT1B (100 mg/kg; lung; daily; 4 weeks) effectively lowers xenograft tumor growth in mice [1]. IMT1B decreases mtDNA levels and respiratory chain subunit levels in malignancies [1]. Excellent side wall bioavailability (101% in mice) and Cmax (5149 ng/mL in mice) in mouse models (10 mg/kg in mice)[1].
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| Cell Assay |
Cell Viability Assay[1]
Cell Types: A2780 Cell Tested Concentrations: 0.01 nM, 1 nM, 10 nM, 100 nM, 1 μM, 10 μM Incubation Duration: 72 hrs (hours), 96 hrs (hours), 168 hrs (hours) Experimental Results: significant increase in decrease [1]. Cell viability was dose-dependent. |
| Animal Protocol |
Animal/Disease Models: 7-9 weeks old female BALB/c nude mice, A2780 cell xenografts [1]
Doses: 100 mg/kg Route of Administration: Orally, one time/day, 4 times a week. Experimental Results: The tumor volume was Dramatically diminished. Animal/Disease Models: Mouse[1] Doses: 1 mg/kg, intravenous (iv) (iv)injection; oral 10 mg/kg (pharmacokinetic/PK/PK analysis) Route of Administration: intravenous (iv) (iv)administration and oral administration Experimental Results: Oral bioavailability (101% ), Cmax (5149 ng/mL), T1/2 (1.88 h). |
| References |
| Molecular Formula |
C24H21CLFNO6
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|---|---|
| Molecular Weight |
473.878049612045
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| Exact Mass |
473.104
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| CAS # |
2304621-06-3
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| PubChem CID |
138490769
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| Appearance |
White to off-white solid powder
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| LogP |
3.7
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
33
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| Complexity |
806
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| Defined Atom Stereocenter Count |
2
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| SMILES |
ClC1C=C(C=CC=1C1=CC(=O)OC2C=C(C=CC=21)O[C@H](C)C(N1CCC[C@H](C(=O)O)C1)=O)F
|
| InChi Key |
PFEKWBKJUBCXDT-KGLIPLIRSA-N
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| InChi Code |
InChI=1S/C24H21ClFNO6/c1-13(23(29)27-8-2-3-14(12-27)24(30)31)32-16-5-7-18-19(11-22(28)33-21(18)10-16)17-6-4-15(26)9-20(17)25/h4-7,9-11,13-14H,2-3,8,12H2,1H3,(H,30,31)/t13-,14+/m1/s1
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| Chemical Name |
(S)-1-((R)-2-((4-(2-chloro-4-fluorophenyl)-2-oxo-2H-chromen-7-yl)oxy)propanoyl)piperidine-3-carboxylic acid
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| Synonyms |
LDC 203974IMT1B LDC203974 IMT-1B LDC-203974
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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 : ~250 mg/mL (~527.56 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (4.39 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 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. Solubility in Formulation 2: ≥ 2.08 mg/mL (4.39 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.1102 mL | 10.5512 mL | 21.1024 mL | |
| 5 mM | 0.4220 mL | 2.1102 mL | 4.2205 mL | |
| 10 mM | 0.2110 mL | 1.0551 mL | 2.1102 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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