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| 5mg |
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| Targets |
M-1002 targets hypoxia-inducible factor-2 (HIF-2), a transcription factor that plays a critical role in cellular response to hypoxia. As an agonist, it enhances the affinity of HIF-2α and its partner ARNT (aryl hydrocarbon receptor nuclear translocator) for transcriptional activation. Mechanistically, M-1002 binds to the PAS-B domain of HIF-2α, altering the conformation of the Tyr2 residue. This allosteric modulation promotes the formation of the HIF-2α/ARNT heterodimer, which then binds to hypoxia response elements (HREs) in the DNA to initiate the transcription of target genes. The compound is described as a bidirectional modulator with agonistic activity.
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| ln Vitro |
M1002 (10 μM; 24 h) has the ability to significantly increase HIF-2 target gene expression [1]. Treatment with M1002 (5 μM; 24 hours) demonstrated synergy with inhibitors of the prolyl hydroxylase domain (PHD) [1].
In vitro studies have demonstrated that M-1002 (10 µM; 24 h) significantly increases the expression of HIF-2 target genes in 786-O cells. In Hep3B cells, co-treatment with M-1002 (5 µM; 24 hours) and prolyl hydroxylase domain (PHD) inhibitors showed a synergistic effect, further enhancing the expression of HIF-2 target genes like EPO and NDRG1 compared to treatment with M-1002 alone. The compound's potency is highlighted by an EC50 of 0.44 µM in luciferase reporter gene assays. It is soluble in DMSO at concentrations up to 50 mg/mL (~126.81 mM). |
| ln Vivo |
In vivo activity and specific animal model data for M-1002 are less detailed in the available literature, as its primary application is as a research tool for in vitro and biochemical studies. The compound's role as a HIF-2 agonist suggests it could be used to study conditions related to HIF-2 signaling in living organisms. Its synergy with PHD inhibitors in vitro hints at potential combination strategies for in vivo efficacy studies. For in vivo formulation, it is soluble in a vehicle of 10% DMSO + 90% Corn Oil at a concentration of ≥ 2.5 mg/mL.
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| Enzyme Assay |
In vitro enzyme/receptor binding assays for M-1002 typically involve evaluating its agonistic activity on the HIF-2 transcription factor. A common method is the luciferase reporter gene assay, where cells are transfected with a luciferase reporter construct containing hypoxia response elements (HREs). Cells are treated with varying concentrations of M-1002, and the resulting luciferase activity, which reflects HIF-2 transcriptional activation, is measured. This assay is used to determine the compound's EC50, which has been reported as 0.44 µM. Other assays may include assessing the compound's ability to increase the expression of HIF-2 target genes like EPO and NDRG1 using techniques such as RT-PCR.
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| Cell Assay |
RT-PCR[1]
Cell Types: 786-O cells Tested Concentrations: 10 μM Incubation Duration: 24 hrs (hours) Experimental Results: Compared with the control, it has a significant agonistic effect on the expression of HIF-2 target genes in 786-O cells. RT-PCR[1] Cell Types: Hep3B Cell Tested Concentrations: 5 μM Incubation Duration: 24 hrs (hours) Experimental Results: Co-treatment of M1002 with PHD inhibitors increased the expression of EPO and NDRG1 compared to treatment with M1002 alone. In vitro cell-based assays for M-1002 are performed in cell lines such as 786-O (renal carcinoma) and Hep3B (hepatocellular carcinoma) cells. Typically, cells are treated with the compound at concentrations like 5 µM or 10 µA for 24 hours. Following treatment, the expression of HIF-2 target genes is measured using RT-PCR to quantify changes in mRNA levels. For synergy studies, cells are co-treated with M-1002 and PHD inhibitors, and the combined effect on gene expression is compared to that of each compound alone. Cell viability and other functional assays can also be performed to assess the compound's broader cellular effects. |
| Animal Protocol |
Specific in vivo animal experiment protocols for M-1002 are not extensively detailed in the available literature. However, the compound can be formulated for in vivo administration. A recommended formulation is a solution of 10% DMSO in 90% Corn Oil, which can achieve a concentration of ≥ 2.5 mg/mL (6.34 mM). Alternatively, a formulation of 10% DMSO + 90% Corn Oil at 1 mg/mL (2.54 mM) has also been described. The route of administration and dosing regimen would depend on the specific experimental design. Such studies would likely involve administering the compound to animal models to evaluate its pharmacokinetic properties and its effects on HIF-2-related pathways in vivo.
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| ADME/Pharmacokinetics |
Detailed pharmacokinetic (PK) properties of M-1002 are not extensively characterized in the provided sources. However, some physicochemical properties relevant to PK can be inferred. The compound has a calculated LogP of 5.15, indicating high lipophilicity, which may affect its absorption and distribution. It is soluble in DMSO and DMF and can be formulated for in vivo use in a mixture of 10% DMSO and 90% Corn Oil. For storage, the powder is stable at -20°C for up to 3 years and at 4°C for up to 2 years. In solvent, it can be stored at -80°C for 6 months or at -20°C for 1 month. The compound's density is 1.6±0.1 g/cm3 and its boiling point is 414.6±55.0 °C at 760 mmHg.
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| Toxicity/Toxicokinetics |
Specific toxicological data for M-1002 are not provided in the available sources. As a research chemical, its safety profile in humans has not been established. The compound is classified as a research reagent for in vitro and biochemical studies and is not for therapeutic or veterinary use. Standard laboratory safety precautions should be followed when handling M-1002, including the use of appropriate personal protective equipment. Its purity is typically ≥98%, with some suppliers offering ≥99% purity.
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| References | |
| Additional Infomation |
M-1002 is a small-molecule allosteric agonist of HIF-2, developed as an analog of M1001. It enhances the affinity of HIF-2α and ARNT for transcriptional activation. The compound acts by altering the conformation of the Tyr2 residue in the HIF-2α PAS-B domain. It shows synergy with prolyl hydroxylase domain (PHD) inhibitors, suggesting potential for combination studies. M-1002 is a valuable tool for studying HIF-2 biology and has been cited in the literature. It is supplied as a solid powder with a purity of ≥98% and is soluble in DMSO. The compound is intended for research use only and is not for human consumption.
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| Molecular Formula |
C15H8F6N2O2S
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| Molecular Weight |
394.2916431427
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| Exact Mass |
394.021
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| CAS # |
823830-85-9
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| PubChem CID |
2220129
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| Appearance |
White to off-white solid powder
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| Density |
1.6±0.1 g/cm3
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| Boiling Point |
414.6±55.0 °C at 760 mmHg
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| Flash Point |
204.6±31.5 °C
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| Vapour Pressure |
0.0±1.0 mmHg at 25°C
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| Index of Refraction |
1.564
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| LogP |
5.15
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
9
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| Rotatable Bond Count |
2
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| Heavy Atom Count |
26
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| Complexity |
645
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C1=CC=C2C(=C1)C(=NS2(=O)=O)NC3=CC(=CC(=C3)C(F)(F)F)C(F)(F)F
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| InChi Key |
BMTRZTPPTZHACH-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C15H8F6N2O2S/c16-14(17,18)8-5-9(15(19,20)21)7-10(6-8)22-13-11-3-1-2-4-12(11)26(24,25)23-13/h1-7H,(H,22,23)
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| Chemical Name |
N-[3,5-bis(trifluoromethyl)phenyl]-1,1-dioxo-1,2-benzothiazol-3-amine
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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 : ~50 mg/mL (~126.81 mM)
DMF : 50 mg/mL (~126.81 mM) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (6.34 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 25.0 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 | 2.5362 mL | 12.6810 mL | 25.3620 mL | |
| 5 mM | 0.5072 mL | 2.5362 mL | 5.0724 mL | |
| 10 mM | 0.2536 mL | 1.2681 mL | 2.5362 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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