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| Targets |
INVIVO-0084 specifically targets the mutant form of isocitrate dehydrogenase 1 (IDH1), specifically the R132H mutation. This mutation is a gain-of-function alteration that causes the enzyme to produce the oncometabolite 2-hydroxyglutarate (2-HG) instead of its normal product, alpha-ketoglutarate. By inhibiting the mutant IDH1 enzyme, INVIVO-0084 reduces 2-HG levels, thereby reversing the aberrant metabolic state and epigenetic changes that drive tumorigenesis.
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| ln Vitro |
Mutated IDH1 is a strong IDH1 R132H inhibitor that is used to treat illnesses or ailments linked to such mutant IDH proteins, including but not limited to problems involving cell proliferation like cancer [1].
In vitro, INVIVO-0084 demonstrates potent activity against the mutant IDH1 R132H enzyme. It has an IC50 of less than 72 nM, indicating high potency. The compound's activity is characterized by its ability to selectively inhibit the mutant enzyme without significantly affecting the wild-type IDH1, which is crucial for minimizing off-target effects. This inhibition leads to a reduction in the levels of the oncometabolite 2-HG in cancer cells, which is a key readout for its efficacy. |
| ln Vivo |
In vivo, INVIVO-0084 is used to study the effects of mutant IDH1 inhibition in animal models of cancer. By reducing the levels of 2-HG, the compound aims to reverse the oncogenic effects of the mutation. This approach has shown promise in preclinical studies, as targeting mutant IDH1 has been validated as a therapeutic strategy in clinical trials with other compounds. Its in vivo efficacy is related to its ability to modulate the metabolic and epigenetic state of tumor cells.
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| Enzyme Assay |
In vitro enzyme/receptor binding studies for INVIVO-0084 typically involve enzyme activity assays. In these assays, the mutant IDH1 R132H enzyme is incubated with its substrate and cofactors in the presence of varying concentrations of the inhibitor. The enzyme's activity is measured by detecting the production of 2-HG or the consumption of NADPH. The IC50 value (<72 nM) is then calculated from the dose-response curve. This confirms the compound's direct binding and inhibition of the mutant enzyme.
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| Cell Assay |
In vitro cellular assays for INVIVO-0084 involve treating cancer cell lines that harbor the IDH1 R132H mutation. The key readouts include measuring the levels of 2-HG in the cells, which should decrease upon treatment. Additionally, the effects on cell proliferation, differentiation, and gene expression (due to changes in DNA and histone methylation) are assessed. These assays are crucial for confirming the compound's mechanism of action and its potential as an anticancer agent.
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| Animal Protocol |
In vivo animal studies for INVIVO-0084 are conducted in xenograft models using tumor cell lines with the IDH1 R132H mutation. Tumor-bearing mice are treated with INVIVO-0084, and endpoints include tumor growth inhibition, measurement of 2-HG levels in the tumor and plasma, and assessment of survival. These studies are essential for evaluating the compound's in vivo efficacy and pharmacokinetic properties, and for validating the therapeutic potential of targeting mutant IDH1.
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| ADME/Pharmacokinetics |
Pharmacokinetic properties of INVIVO-0084 are indicated by its solubility in DMSO (≥34 mg/mL). It has a molecular weight of 466.59 g/mol and a molecular formula of C₂₅H₃₄N₆O₃. The compound has a predicted LogP of 2.31, suggesting moderate lipophilicity. For storage, the powder is stable at -20°C for 3 years. These properties are important for its use in formulation for both in vitro and in vivo studies.
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| Toxicity/Toxicokinetics |
Toxicological data for INVIVO-0084 are limited, as it is a research compound not intended for human use. Its primary value is as a tool to study the biology of mutant IDH1. While specific toxicity profiles are not detailed, its mechanism of reducing 2-HG levels is expected to have a specific effect on cancer cells with the mutation, which is the basis for its therapeutic potential. However, comprehensive safety studies are not available in the public domain.
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| References | |
| Additional Infomation |
INVIVO-0084 is a research-use-only chemical compound that acts as a potent inhibitor of the mutant IDH1 R132H enzyme. It is also known as Mutant IDH1 inhibitor and has the CAS number 1429180-08-4. This compound is part of a class of drugs that target the metabolic vulnerabilities of cancer cells. By inhibiting the production of the oncometabolite 2-HG, it holds promise for treating IDH1-mutant cancers, a strategy that has been clinically validated with other compounds. It is not an approved drug.
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| Molecular Formula |
C25H34N6O3
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| Molecular Weight |
466.59
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| Exact Mass |
466.269
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| CAS # |
1429180-08-4
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| PubChem CID |
71542482
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| Appearance |
White to light yellow solid powder
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| Density |
1.2±0.1 g/cm3
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| Boiling Point |
651.8±65.0 °C at 760 mmHg
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| Flash Point |
348.0±34.3 °C
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| Vapour Pressure |
0.0±2.0 mmHg at 25°C
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| Index of Refraction |
1.608
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| LogP |
2.31
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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 |
7
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| Heavy Atom Count |
34
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| Complexity |
690
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| Defined Atom Stereocenter Count |
2
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| SMILES |
C[C@@H](C1=CC=C(C=C1)CN2CCN(CC2)C(=O)C)NC3=NC=CC(=N3)N4[C@H](COC4=O)C(C)C
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| InChi Key |
BEWLUEOYYPKPQL-PGRDOPGGSA-N
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| InChi Code |
InChI=1S/C25H34N6O3/c1-17(2)22-16-34-25(33)31(22)23-9-10-26-24(28-23)27-18(3)21-7-5-20(6-8-21)15-29-11-13-30(14-12-29)19(4)32/h5-10,17-18,22H,11-16H2,1-4H3,(H,26,27,28)/t18-,22+/m0/s1
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| Chemical Name |
(4S)-3-[2-[[(1S)-1-[4-[(4-acetylpiperazin-1-yl)methyl]phenyl]ethyl]amino]pyrimidin-4-yl]-4-propan-2-yl-1,3-oxazolidin-2-one
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| Synonyms |
INVIVO 0084; INVIVO-0084; Mutant IDH1 inhibitor
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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 : ≥ 34 mg/mL (~72.87 mM)
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| 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 | 2.1432 mL | 10.7160 mL | 21.4321 mL | |
| 5 mM | 0.4286 mL | 2.1432 mL | 4.2864 mL | |
| 10 mM | 0.2143 mL | 1.0716 mL | 2.1432 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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