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| Targets |
PKUMDL-WQ-2101 targets phosphoglycerate dehydrogenase (PHGDH). PHGDH is the first enzyme in the serine biosynthesis pathway, catalyzing the conversion of 3-phosphoglycerate to 3-phosphohydroxypyruvate. Many cancer cells are dependent on de novo serine synthesis for growth and survival, making PHGDH a promising anticancer target. PKUMDL-WQ-2101 is a non-NAD+-competing allosteric inhibitor that binds to allosteric site I, inhibiting the enzyme without competing with its NAD+ cofactor.
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| ln Vitro |
At micromolar concentrations, PKUMDL-WQ-2101 (72 hours) demonstrated a dose-dependent decrease of cell viability and demonstrated an excellent coupling to PHGDH-positive breast cancer cell lines. In two PHGDH-containing breast cancer cell lines (MDA-MB-468 and HCC70), PKUMDL-WQ-2101 demonstrated anti-tumor activity of 7.70 μM and 10.8 μM, respectively [1]. Similar to PHGDH gene deletion, PKUMDL-WQ-2101 (2.5–40 μM; 24 hours) reduces de novo serine synthesis and consumption downstream of serine synthesis through the MDA-MB PKUMDL-WQ-2101 (37 μM; 24 hours) route [1]. Marketing of -468 cells in the cell cycle[1]. [1]
PKUMDL-WQ-2101 demonstrates potent inhibition of PHGDH enzyme activity with an IC50 of 34.8 μM. It is a non-NAD+-competing allosteric inhibitor, meaning it binds to an allosteric site rather than the active site. The compound exhibits antitumor activity in vitro in breast cancer cell lines overexpressing PHGDH, with EC50 values of 7.7 and 10.8 μM in MDA-MB-468 and HCC-70 cells, respectively. It selectively inhibits de novo serine synthesis in cancer cells. |
| ln Vivo |
In nude mice with MDA-361 human breast cancer tumors, PKI-179 (5–50 mg/kg; administered orally once day for 40 days) suppresses tumor growth and is well tolerated [1]. PKI-179 (50 mg/kg; oral) has positive inhibitory effects on PI3K signaling in mice that are not wearing any clothes and have MDA361 tumor xenograft tumors [1]. PKI-179 has a lengthy half-life (>60 minutes) and good oral bioavailability (98% in naked mice, 46% in rats, 38% in monkeys, and 61% in dogs) [1].
PKUMDL-WQ-2101 demonstrates in vivo antitumor activity. It reduces tumor growth in vivo. The compound's ability to inhibit PHGDH and reduce serine synthesis translates to anticancer efficacy in animal models. It selectively targets cancer cells that are dependent on de novo serine synthesis. Detailed in vivo efficacy data are limited in publicly available sources. The compound is a valuable tool for studying PHGDH biology and its role in cancer metabolism. |
| Enzyme Assay |
PHGDH enzyme inhibition assays are performed using recombinant human PHGDH enzyme. The enzyme is incubated with the substrate 3-phosphoglycerate and the cofactor NAD+ in assay buffer (50 mM Tris-HCl pH 8.0, 100 mM KCl, 5 mM MgCl2, 1 mM DTT). The reaction is incubated at 37°C for 30-60 minutes. The product 3-phosphohydroxypyruvate is detected by coupling to a diaphorase/resazurin system or by HPLC. Test compounds are serially diluted and added to the reaction mixture. IC50 values are determined by non-linear regression analysis. Each concentration is tested in duplicate. The allosteric mechanism is confirmed by NAD+ competition studies.
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| Cell Assay |
Cell Viability Assay[1]
Cell Types: MDA-MB-468 Cell Tested Concentrations: 2.5 μM, 5.0 μM, 20 μM and 40 μM Incubation Duration: 24 hrs (hours) Experimental Results: Causes cell cycle arrest. Cellular PHGDH inhibition is evaluated in breast cancer cell lines overexpressing PHGDH (e.g., MDA-MB-468, HCC-70). Cells are cultured in appropriate media at 37°C with 5% CO2 and treated with PKUMDL-WQ-2101 at various concentrations (1-100 μM) for 24-72 hours. De novo serine synthesis is measured by tracing [13C]-glucose or [13C]-glutamine incorporation into serine using LC-MS. Cell viability is assessed using MTT or CellTiter-Glo assays. Proliferation and apoptosis are evaluated. Each experiment includes known PHGDH inhibitors as positive controls and vehicle controls. |
| Animal Protocol |
Animal/Disease Models: NOD.CB17 Scid/J mice injected with MDA-MB-468 cells [1]
Doses: 5 mg/kg, 10 mg/kg, 20 mg/kg Route of Administration: intraperitoneal (ip) injection; daily; continued for 30 Day Experimental Results: Demonstrated significant inhibitory effect on MDA-MB-468 xenografts. In vivo efficacy is evaluated in mouse xenograft models using PHGDH-overexpressing breast cancer cell lines. PKUMDL-WQ-2101 is administered orally or intraperitoneally at doses typically ranging from 10-100 mg/kg. Tumor growth is monitored by caliper measurements. At study endpoint, tumors are harvested for histopathological analysis and biochemical assays (serine levels, PHGDH activity, NAD+/NADH ratio). Pharmacokinetic parameters are assessed in parallel. Body weight and clinical signs are monitored throughout the study. Sample sizes typically range from 6-10 animals per group. |
| ADME/Pharmacokinetics |
PKUMDL-WQ-2101 has a molecular weight of 317.25 g/mol and a molecular formula of C14H11N3O6. Solubility: soluble to 100 mM in DMSO. Purity: ≥98% by HPLC. Storage: typically at -20°C. Bioavailability, half-life, and tissue distribution data are not publicly available. The compound is a research tool for studying PHGDH inhibition and cancer metabolism.
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| Toxicity/Toxicokinetics |
Limited toxicology data are available for PKUMDL-WQ-2101. As a PHGDH inhibitor targeting serine synthesis, potential toxicities may include effects on normal tissues that require serine synthesis. Standard toxicology studies would include acute and subchronic toxicity in rodents, genotoxicity screening, and evaluation of effects on metabolism. No clinical trials have been reported for this compound. The compound is intended for research use only.
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| References | |
| Additional Infomation |
PKUMDL-WQ-2101 is also known as PKUMDL WQ 2101. Its chemical name is 2,4-dihydroxy-N'-(2-hydroxy-5-nitrobenzylidene)benzohydrazide. It is a non-NAD+-competing allosteric inhibitor of PHGDH with an IC50 of 34.8 μM. It exhibits antitumor activity and selectively inhibits de novo serine synthesis in cancer cells. No clinical trials or regulatory approvals have been reported. The compound is for research use only.
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| Molecular Formula |
C14H11N3O6
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| Molecular Weight |
317.253643274307
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| Exact Mass |
317.064
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| CAS # |
304481-72-9
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| PubChem CID |
135403154
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| Appearance |
Light yellow to yellow solid powder
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| Density |
1.5±0.1 g/cm3
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| Index of Refraction |
1.677
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| LogP |
4.51
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| Hydrogen Bond Donor Count |
4
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
3
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| Heavy Atom Count |
23
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| Complexity |
466
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C1=CC(=C(C=C1[N+](=O)[O-])/C=N/NC(=O)C2=C(C=C(C=C2)O)O)O
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| InChi Key |
OXONIXZPWKJHMW-VIZOYTHASA-N
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| InChi Code |
InChI=1S/C14H11N3O6/c18-10-2-3-11(13(20)6-10)14(21)16-15-7-8-5-9(17(22)23)1-4-12(8)19/h1-7,18-20H,(H,16,21)/b15-7+
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| Chemical Name |
2,4-dihydroxy-N-[(E)-(2-hydroxy-5-nitrophenyl)methylideneamino]benzamide
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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 : ~125 mg/mL (~394.01 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 | 3.1521 mL | 15.7604 mL | 31.5209 mL | |
| 5 mM | 0.6304 mL | 3.1521 mL | 6.3042 mL | |
| 10 mM | 0.3152 mL | 1.5760 mL | 3.1521 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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