| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 25mg |
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| Targets |
BMS-978587 targets indoleamine 2,3-dioxygenase 1 (IDO-1). IDO1 is a key enzyme in the kynurenine pathway that is often overexpressed in tumors and antigen-presenting cells. By depleting tryptophan and producing immunosuppressive kynurenines, IDO1 contributes to an immune-tolerant microenvironment that allows tumors to evade immune surveillance.
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| ln Vitro |
In human IDO1/HEK293 cells, BMS-978587 (IDO-IN-4) (Compound Example 1 Enantiomer 1) functions as an IDO-1 inhibitor [1].
BMS-978587 is a potent IDO1 inhibitor with an IC50 value of 8 nM in human IDO1/HEK293 cells. This indicates that the compound is highly effective at inhibiting the enzyme's activity. The inhibition of IDO1 leads to a reduction in kynurenine production and an increase in tryptophan levels, which can reactivate T cells and enhance the antitumor immune response. |
| ln Vivo |
In vivo, BMS-978587 has been shown to have anticancer and immunomodulatory activity. By inhibiting IDO1, the compound can suppress the immunosuppressive effects of the kynurenine pathway. This can lead to an increase in the number and activity of tumor-infiltrating lymphocytes, resulting in tumor growth inhibition. It is being investigated as a potential immunotherapeutic agent.
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| Enzyme Assay |
The inhibitory activity of BMS-978587 on IDO1 is typically measured in a cell-free enzyme assay. Recombinant human IDO1 is incubated with L-tryptophan and varying concentrations of the compound. The production of N-formylkynurenine, the product of the IDO1 reaction, is measured spectrophotometrically or by HPLC. The IC50 is determined from the concentration-response curve.
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| Cell Assay |
Cellular assays are performed using cells that overexpress IDO1, such as human IDO1/HEK293 cells. These cells are treated with BMS-978587, and the production of kynurenine in the culture supernatant is measured, typically by HPLC or a colorimetric assay. The compound's ability to inhibit cellular IDO1 activity is quantified by determining its IC50.
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| Animal Protocol |
In vivo efficacy of BMS-978587 is evaluated in syngeneic mouse tumor models. Mice bearing tumors that express IDO1 are treated with the compound, either alone or in combination with other immunotherapies like anti-PD-1 or anti-CTLA-4 antibodies. Tumor growth is monitored, and immune cell infiltration and activation are analyzed by flow cytometry.
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| ADME/Pharmacokinetics |
BMS-978587 has a molecular weight of 437.57 g/mol and a chemical formula of C26H35N3O3. As a small molecule, it is expected to have good oral bioavailability. Pharmacokinetic studies in preclinical species would involve measuring plasma concentrations of the compound after administration to determine its half-life, clearance, and volume of distribution.
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| Toxicity/Toxicokinetics |
BMS-978587 is generally well-tolerated in preclinical studies. As an immunomodulatory agent, its toxicity is primarily related to its mechanism of action, which may involve the disruption of tryptophan metabolism. Extensive toxicology studies are required to fully characterize its safety profile and determine a safe therapeutic window.
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| References | |
| Additional Infomation |
BMS-978587 is a research-grade small molecule IDO1 inhibitor. It is extracted from patent WO2014150677A1 as Compound example 1 enantiomer 1. It is a valuable tool for studying the role of the kynurenine pathway in immune suppression and cancer, and for evaluating the potential of IDO1 inhibition as a therapeutic strategy.
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| Molecular Formula |
C26H35N3O3
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|---|---|
| Molecular Weight |
437.574406862259
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| Exact Mass |
437.267
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| CAS # |
1629125-65-0
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| PubChem CID |
118676157
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| Appearance |
Off-white to yellow solid powder
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| Density |
1.2±0.1 g/cm3
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| Boiling Point |
532.6±50.0 °C at 760 mmHg
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| Flash Point |
275.9±30.1 °C
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| Vapour Pressure |
0.0±1.5 mmHg at 25°C
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| Index of Refraction |
1.633
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| LogP |
5.74
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
9
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| Heavy Atom Count |
32
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| Complexity |
620
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| Defined Atom Stereocenter Count |
2
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| SMILES |
CC1=CC=C(C=C1)NC(=O)NC2=C(C=CC(=C2)[C@H]3C[C@H]3C(=O)O)N(CC(C)C)CC(C)C
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| InChi Key |
VZYCPKLOYXSKAB-FGZHOGPDSA-N
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| InChi Code |
InChI=1S/C26H35N3O3/c1-16(2)14-29(15-17(3)4)24-11-8-19(21-13-22(21)25(30)31)12-23(24)28-26(32)27-20-9-6-18(5)7-10-20/h6-12,16-17,21-22H,13-15H2,1-5H3,(H,30,31)(H2,27,28,32)/t21-,22-/m1/s1
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| Chemical Name |
(1R,2S)-2-[4-[bis(2-methylpropyl)amino]-3-[(4-methylphenyl)carbamoylamino]phenyl]cyclopropane-1-carboxylic acid
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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 : ≥ 100 mg/mL (~228.53 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.71 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 25.0 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: ≥ 2.5 mg/mL (5.71 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 | 2.2853 mL | 11.4267 mL | 22.8535 mL | |
| 5 mM | 0.4571 mL | 2.2853 mL | 4.5707 mL | |
| 10 mM | 0.2285 mL | 1.1427 mL | 2.2853 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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