| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
|
||
| 10mg |
|
||
| 50mg |
|
||
| 100mg |
|
||
| 250mg | |||
| Other Sizes |
| Targets |
PKUMDL-WQ-2201 targets phosphoglycerate dehydrogenase (PHGDH), the first and rate-limiting enzyme of the de novo serine synthesis pathway. PHGDH catalyzes the conversion of 3-phosphoglycerate to 3-phosphohydroxypyruvate, a key step in serine biosynthesis. PKUMDL-WQ-2201 is a non-NAD+-competing allosteric inhibitor of PHGDH with an IC50 of 35.7 μM. It binds to site II of the enzyme. By inhibiting PHGDH, the compound reduces serine synthesis in cancer cells, which is particularly important for tumors that are dependent on de novo serine synthesis for growth and survival.
|
|---|---|
| ln Vitro |
With EC50 values of 7.7 μM (MDA-MB-468) and 10.8 μM (HCC70), PKUMDL-WQ-2201 (10 nM-100 μM; 3 d) exhibits excellent localization and inhibitory effects on PHGDH in breast cancer cell lines [1].
In vitro, PKUMDL-WQ-2201 is a potent and selective non-NAD+-competing allosteric inhibitor of PHGDH with an IC50 of 35.7 μM. It inhibits de novo serine synthesis in cancer cells. The compound shows inhibitory activity against both wild-type and mutant PHGDH enzymes. Its activity is typically measured using enzyme assays with purified PHGDH and substrate, as well as cell-based assays measuring serine production. These in vitro studies establish PKUMDL-WQ-2201 as a valuable tool for studying serine-dependent tumor metabolism. |
| ln Vivo |
PKUMDL-WQ-2201 (5–20 mg/kg; intraperitoneal injection; once daily for 30 days) significantly inhibits the growth of tumors but does not alter MDA-MB-468 xenografts as compared to the probe model[1].
In vivo, PKUMDL-WQ-2201 reduces tumor growth. As a PHGDH inhibitor, it has been studied for its potential to inhibit serine-dependent tumor metabolism. However, specific in vivo protocols and results, such as efficacy in animal models, are not detailed in standard product descriptions. The compound provides a metabolic intervention strategy for studying serine-dependent tumor metabolism. |
| Enzyme Assay |
In vitro enzyme assays for PKUMDL-WQ-2201 measure its inhibition of PHGDH activity. PHGDH enzyme is incubated with its substrate (3-phosphoglycerate) and cofactor (NAD+) in the presence of varying concentrations of PKUMDL-WQ-2201. The production of 3-phosphohydroxypyruvate is measured, and the IC50 is determined from the dose-response curve. For PKUMDL-WQ-2201, the IC50 is 35.7 μM. The compound's allosteric mechanism is confirmed by the lack of competition with NAD+.
|
| Cell Assay |
In vitro cell-based assays for PKUMDL-WQ-2201 are used to study its effects on serine synthesis in cancer cells. Cancer cells are treated with PKUMDL-WQ-2201 at various concentrations, and the levels of serine and other metabolites are measured by LC-MS/MS. Cell proliferation is assessed using standard assays such as MTT or CellTiter-Glo. The compound's ability to inhibit cell growth and reduce serine synthesis is measured. These assays confirm the compound's cellular activity as a PHGDH inhibitor.
|
| Animal Protocol |
In vivo animal experiments for PKUMDL-WQ-2201 are conducted in mouse models of cancer. In a typical study, mice bearing xenograft tumors are treated with PKUMDL-WQ-2201, and tumor growth is monitored. The compound's ability to reduce tumor growth is assessed. However, specific protocols for PKUMDL-WQ-2201 are not detailed in standard product descriptions. Its use is limited to research applications to study serine-dependent tumor metabolism.
|
| ADME/Pharmacokinetics |
PKUMDL-WQ-2201 has a molecular weight of 351.81 g/mol and a molecular formula of C15H14ClN3O3S. It is a solid compound with a purity of ≥98%. It is soluble in DMSO and other organic solvents. For storage, it is recommended to keep the powder at -20°C. Detailed pharmacokinetic properties such as absorption, distribution, metabolism, and excretion (ADME) have not been extensively characterized. As a research compound, its stability is maintained by proper storage as a dry powder.
|
| Toxicity/Toxicokinetics |
Detailed toxicity data for PKUMDL-WQ-2201 is not provided in standard product descriptions. As a research compound, its toxicity profile has not been extensively characterized. PKUMDL-WQ-2201 is a PHGDH inhibitor, and its toxicity would be related to its effects on serine synthesis in normal tissues. However, comprehensive toxicological studies have not been reported. As with all research chemicals, standard laboratory safety precautions should be followed when handling PKUMDL-WQ-2201. Its use is limited to research applications and it is not intended for human or veterinary use.
|
| References | |
| Additional Infomation |
PKUMDL-WQ-2201 is a research compound and is not approved for any clinical or therapeutic use. It is a potent and selective non-NAD+-competing allosteric inhibitor of phosphoglycerate dehydrogenase (PHGDH) with an IC50 of 35.7 μM. PKUMDL-WQ-2201 inhibits de novo serine synthesis in cancer cells and reduces tumor growth. The compound is a research tool for studying serine-dependent tumor metabolism and provides a metabolic intervention strategy. Its mechanism of action involves allosteric inhibition of PHGDH, reducing serine synthesis and thereby inhibiting the growth of serine-dependent tumors.
|
| Exact Mass |
351.044
|
|---|---|
| CAS # |
592474-91-4
|
| PubChem CID |
6875399
|
| Appearance |
Light yellow to yellow solid powder
|
| Density |
1.4±0.1 g/cm3
|
| Boiling Point |
523.5±60.0 °C at 760 mmHg
|
| Flash Point |
270.4±32.9 °C
|
| Vapour Pressure |
0.0±1.4 mmHg at 25°C
|
| Index of Refraction |
1.647
|
| LogP |
2.79
|
| Hydrogen Bond Donor Count |
3
|
| Hydrogen Bond Acceptor Count |
5
|
| Rotatable Bond Count |
5
|
| Heavy Atom Count |
23
|
| Complexity |
463
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
ClC1=C(C(=O)O)C=CC(=C1)C1=CC=C(/C=N\NC(NCC)=S)O1
|
| InChi Key |
XPACBFAEZIPDRT-QGMBQPNBSA-N
|
| InChi Code |
InChI=1S/C15H14ClN3O3S/c1-2-17-15(23)19-18-8-10-4-6-13(22-10)9-3-5-11(14(20)21)12(16)7-9/h3-8H,2H2,1H3,(H,20,21)(H2,17,19,23)/b18-8+
|
| Chemical Name |
2-chloro-4-[5-[(E)-(ethylcarbamothioylhydrazinylidene)methyl]furan-2-yl]benzoic acid
|
| HS Tariff Code |
2934.99.9001
|
| 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)
|
| Solubility (In Vitro) |
DMSO : ~100 mg/mL (~284.24 mM)
|
|---|---|
| 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.) |
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.
|
|
|
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
