| Size | Price | Stock | Qty |
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| Other Sizes |
Purity: =98.56%
| Targets |
4-CPPC selectively and reversibly inhibits human macrophage migration inhibitory factor-2 (MIF-2, also known as D-DT) with a competitive binding mode. The inhibition constant (Ki) for MIF-2 is 33 ± 0.7 µM, and for the related protein MIF-1, it is 431 ± 37 µM, resulting in a 13-fold selectivity for MIF-2 over MIF-1.[1]
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| ln Vitro |
4-CPPC is reported as the first reversible and selective small-molecule inhibitor of MIF-2.[1]
The compound competitively inhibits the tautomerase activity of both MIF-1 and MIF-2, as determined using p-hydroxyphenylpyruvate (HPP) as the substrate in an enzymatic assay. Lineweaver-Burk plots confirmed the competitive inhibition mechanism.[1] The binding of 4-CPPC to MIF-2 is characterized by an induced fit mechanism, where the C-terminal residues V113–L117 of MIF-2 undergo significant conformational changes to accommodate the inhibitor in the active site pocket. In the crystal structure, electron density for residues M114–L117 is absent upon 4-CPPC binding, indicating increased flexibility in this region.[1] The pyridine-2,5-dicarboxylic acid moiety of 4-CPPC is buried within the MIF-2 active site, forming electrostatic interactions with K32, R36, and K109, hydrogen bonds with P1, S63, I64, and K109, polar interactions with S63 and S104, and hydrophobic interactions with P1, F2, I64, and I107. The benzoic acid moiety is exposed to the solvent and does not interact with the protein.[1] Structural alignment and comparison show that 4-CPPC selectivity for MIF-2 over MIF-1 is due to differences in the active site composition. In MIF-1, bulky residues Y36, Y95, and F113 create steric hindrance and clash with the benzoic acid moiety of 4-CPPC, preventing optimal binding.[1] |
| Enzyme Assay |
MIF Tautomerase Activity Inhibition Assay: A stock solution of p-hydroxyphenylpyruvate (HPP) substrate (100 mM) was freshly prepared in 50 mM ammonium acetate buffer (pH 6.2) and incubated overnight at room temperature to favor the keto form. A reaction mixture containing borate buffer (final concentration 0.420 M), recombinant human MIF-1 or MIF-2 protein (final concentration 100 nM or 250 nM, respectively), and 4-CPPC (dissolved in DMSO) was transferred to a UV-transparent 96-well plate containing varying final concentrations of HPP (0 to 2 mM). The final DMSO concentration was 1%. The enzymatic conversion of HPP keto form to its enol form, which complexes with borate, was monitored by measuring the increase in absorbance at 306 nm (ε306 = 11400 M⁻¹ cm⁻¹) over 90 seconds. All experiments were performed in triplicate. Initial velocity data were used to generate Lineweaver-Burk plots to determine the inhibition constant (Ki) and the mode of inhibition.[1]
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| References | |
| Additional Infomation |
4-CPPC (4-(3-carboxyphenyl)-2,5-pyridinedicarboxylic acid) was discovered via in silico screening (details in a separate manuscript in preparation by R. Bucala).[1]
The crystal structure of the MIF-2/4-CPPC complex was determined at 1.40 Å resolution (PDB entry 6C5F). Apo-MIF-2 crystals were grown using the hanging drop method with a well solution containing PEG 4000, sodium citrate (pH 5.8), and ammonium acetate. For soaking, apo-MIF-2 crystals were transferred to a solution containing 0.2 M 4-CPPC, incubated for 24 hours, and then flash-frozen for X-ray data collection.[1] 4-CPPC represents a valuable chemical tool to distinguish the biological functions of MIF-2 from those of MIF-1 in systems where both proteins are co-expressed, such as in cancer, inflammation, and cardiac ischemia/reperfusion injury. It provides a structural basis for the design of more potent and selective MIF-2 inhibitors, particularly by modifying the solvent-exposed benzoic acid moiety.[1] |
| Molecular Formula |
C14H9NO6
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|---|---|
| Molecular Weight |
287.23
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| Exact Mass |
287.042
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| CAS # |
29553-70-6
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| PubChem CID |
893698
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| Appearance |
White to off-white solid powder
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| Density |
1.5±0.1 g/cm3
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| Boiling Point |
595.2±50.0 °C at 760 mmHg
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| Flash Point |
313.8±30.1 °C
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| Vapour Pressure |
0.0±1.8 mmHg at 25°C
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| Index of Refraction |
1.675
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| LogP |
1.01
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
21
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| Complexity |
437
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C1=CC(=CC(=C1)C(=O)O)C2=CC(=NC=C2C(=O)O)C(=O)O
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| InChi Key |
NBVHLJGGHJLTGM-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C14H9NO6/c16-12(17)8-3-1-2-7(4-8)9-5-11(14(20)21)15-6-10(9)13(18)19/h1-6H,(H,16,17)(H,18,19)(H,20,21)
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| Chemical Name |
4-(3-carboxyphenyl)pyridine-2,5-dicarboxylic acid
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| Synonyms |
4CPPC 4-CPPC 4 CPPC
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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 (~348.17 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 | 3.4815 mL | 17.4077 mL | 34.8153 mL | |
| 5 mM | 0.6963 mL | 3.4815 mL | 6.9631 mL | |
| 10 mM | 0.3482 mL | 1.7408 mL | 3.4815 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.
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT05602142 | NOT YET RECRUITING | Drug: [11C]CPPC PET ligand | ALS | Johns Hopkins University | 2024-07 | Phase 1 Phase 2 |
| NCT04749433 | TERMINATED | Drug: [11C]CPPC Injection | Amyotrophic Lateral Sclerosis | Johns Hopkins University | 2021-09-01 | Phase 1 |
| NCT06223971 | RECRUITING | Drug: [11C]CPPC Injection Drug: [11C]CPPC Injection |
COVID Long-Haul | Johns Hopkins University | 2024-07-01 | Early Phase 1 |
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