| Size | Price | |
|---|---|---|
| 500mg | ||
| 1g | ||
| Other Sizes |
| Targets |
The target of Dimethyl-F-OICR-9429-COOH is WD40 repeat domain protein 5 (WDR5). WDR5 is a core component of the Mixed-Lineage Leukemia (MLL) complex, playing a critical role in histone H3 lysine 4 (H3K4) methylation and the regulation of gene transcription. By binding with high affinity to the surface of WDR5, this ligand can competitively disrupt the WDR5-MLL interaction. In PROTAC applications, it serves as the target protein recognition module, directing WDR5 to an E3 ubiquitin ligase and triggering its proteasome-dependent degradation. The carboxylic acid functionality in this derivative facilitates linker conjugation for PROTAC construction.
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| ln Vitro |
This compound is primarily used for PROTAC synthesis rather than independent biological evaluation. Its parent compound OICR-9429 exhibits a WDR5 binding affinity Kd of 24-93 nM in vitro and demonstrates antiproliferative activity across various cancer cell lines. As a WDR5 ligand, Dimethyl-F-OICR-9429-COOH retains binding capability through a mechanism similar to OICR-9429. In vitro, PROTAC molecules constructed using this ligand exploit the intracellular ubiquitin-proteasome system to achieve selective degradation of the target protein WDR5.
One ligand is for an E3 ubiquitin ligase, and the other is for the target protein; these two ligands are joined by a linker to form PROTACs. The intracellular ubiquitin-proteasome system is utilized by PROTACs to specifically destroy target proteins[1]. |
| ln Vivo |
This compound is currently positioned as an intermediate tool for PROTAC synthesis rather than a candidate molecule for direct in vivo pharmacodynamic evaluation. The in vivo antitumor activity of complete PROTAC molecules constructed from this ligand depends on the overall molecular design (involving the synergistic action of the WDR5 ligand, linker, and E3 ligase ligand), and no in vivo data based on this ligand have been reported.
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| Enzyme Assay |
The binding affinity of WDR5 ligands can be assessed using surface plasmon resonance (SPR) or fluorescence polarization (FP) techniques. For typical assays with this class of compounds: recombinant WDR5 protein is immobilized on a chip or in a reaction system, and various concentrations of Dimethyl-F-OICR-9429-COOH (0-1000 nM) are dissolved in binding buffer (e.g., PBS + 0.005% Tween-20) and incubated with the WDR5 protein to measure binding signals. The parent compound OICR-9429 has a measured Kd of 24 nM in such systems. This ligand derivative retains WDR5 binding capability through its carboxylic acid modification and serves as a target protein recognition module for PROTAC construction.
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| Cell Assay |
The cell assay protocol for Dimethyl-F-OICR-9429-COOH itself has not been reported in the published literature, as this compound is an intermediate for PROTAC synthesis. A typical protocol for evaluating cellular degradation activity of PROTAC molecules constructed from this ligand is as follows: Exponentially growing WDR5-high cancer cells (e.g., MLL-rearranged acute myeloid leukemia cell lines) are seeded into 96-well plates at densities of 5×10³-1×10⁴ cells/well, cultured overnight, and then treated with various concentrations of PROTAC compounds (0.1-1000 nM) for 24-72 hours. WDR5 protein levels are detected by Western blot to calculate DC₅₀ and Dmax. Cell viability can also be assessed using MTT or CellTiter-Glo assays.
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| Animal Protocol |
The in vivo animal assay protocol for Dimethyl-F-OICR-9429-COOH itself has not been reported in the published literature. This compound is currently used primarily for PROTAC synthesis rather than direct in vivo administration. A standard protocol for in vivo evaluation of PROTAC molecules is as follows: Six-to-eight-week-old female nude mice are subcutaneously inoculated with WDR5-driven cancer cell lines (5×10⁶ cells/100 μL PBS). When tumor volumes reach approximately 100-150 mm³, animals are randomly assigned to treatment groups. PROTAC compounds are administered via intraperitoneal or intravenous injection, with tumor volume and body weight measured 2-3 times weekly.
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| ADME/Pharmacokinetics |
This compound is an intermediate ligand for PROTAC synthesis, and its own ADME parameters have not been independently characterized. Solubility information is available for reference: it is soluble in DMSO at approximately 200 mg/mL (365.96 mM). Common in vivo injection formulation recipes include DMSO : Tween 80 : saline = 10 : 5 : 85. This compound is intended for research use only, and its pharmacokinetic parameters do not possess independent preclinical pharmacological significance.
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| Toxicity/Toxicokinetics |
Systematic toxicological data for Dimethyl-F-OICR-9429-COOH are currently limited. This product is explicitly stated for scientific research use only and is not for human therapeutic applications. It is classified as a PROTAC synthesis intermediate, with safety considerations primarily related to chemical handling. The powder can be stored at -20°C protected from light for 3 years, at 4°C for 2 years, and in solution at -80°C for 6 months or at -20°C for 1 month. Regarding the WDR5 target mechanism, the potential impact of long-term inhibition or degradation of this pathway on normal cells requires further investigation.
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| References |
| Molecular Formula |
C27H26F4N4O4
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|---|---|
| Molecular Weight |
546.513360500336
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| Exact Mass |
546.189
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| CAS # |
2407458-49-3
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| PubChem CID |
148647697
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| Appearance |
Light brown to brown solid powder
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| LogP |
1
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
10
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
39
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| Complexity |
1020
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| Defined Atom Stereocenter Count |
2
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| SMILES |
C1(C2=CC=C(N3C[C@H](C)N(C)[C@H](C)C3)C(NC(C3C(C(F)(F)F)=CC(=O)NC=3)=O)=C2)=C(F)C=CC(C(O)=O)=C1
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| InChi Key |
NLHFYALGJZKULH-GASCZTMLSA-N
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| InChi Code |
InChI=1S/C27H26F4N4O4/c1-14-12-35(13-15(2)34(14)3)23-7-5-16(18-8-17(26(38)39)4-6-21(18)28)9-22(23)33-25(37)19-11-32-24(36)10-20(19)27(29,30)31/h4-11,14-15H,12-13H2,1-3H3,(H,32,36)(H,33,37)(H,38,39)/t14-,15+
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| Chemical Name |
4-fluoro-3-[3-[[6-oxo-4-(trifluoromethyl)-1H-pyridine-3-carbonyl]amino]-4-[(3S,5R)-3,4,5-trimethylpiperazin-1-yl]phenyl]benzoic acid
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| Synonyms |
Dimethyl-F-OICR-9429-COOH; 2407458-49-3; 6-fluoro-3'-[6-oxo-4-(trifluoromethyl)-1,6-dihydropyridine-3-amido]-4'-[(3R,5S)-3,4,5-trimethylpiperazin-1-yl]-[1,1'-biphenyl]-3-carboxylic acid; orb1984563; NLHFYALGJZKULH-GASCZTMLSA-N;
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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 Note: This product requires protection from light (avoid light exposure) during transportation and storage. |
| 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 : ~200 mg/mL (~366.0 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 | 1.8298 mL | 9.1490 mL | 18.2979 mL | |
| 5 mM | 0.3660 mL | 1.8298 mL | 3.6596 mL | |
| 10 mM | 0.1830 mL | 0.9149 mL | 1.8298 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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