| Size | Price | Stock | Qty |
|---|---|---|---|
| 100mg |
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| Other Sizes |
| Targets |
PHGDH-IN-3 specifically targets phosphoglycerate dehydrogenase (PHGDH), the rate-limiting enzyme of the serine biosynthesis pathway. It exhibits an IC50 of 2.8 μM against PHGDH and demonstrates high binding affinity for the PHGDH protein with a Kd value of 2.33 μM.
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| ln Vitro |
PHGDH-IN-3 (compound D8) exhibits strong enzymatic inhibitory action, as evidenced by its IC50 value of 2.8 μM[1]. PHGDH-IN-3 exhibits a strong affinity for PHGDH protein, as evidenced by its Kd value of 2.33 μM [1]. Antibiotic-induced de novo serine synthesis in MDA-MB-468 cells can be inhibited by PHGDH-IN-3 [1].
In vitro, PHGDH-IN-3 exhibits strong enzymatic inhibitory activity with an IC50 value of 2.8 μM. It demonstrates high binding affinity for the PHGDH protein with a Kd of 2.33 μM. By inhibiting PHGDH, the compound blocks the conversion of 3-phosphoglycerate to serine, reducing de novo serine synthesis in tumor cells and impairing nucleotide synthesis and proliferation. |
| ln Vivo |
PHGDH-IN-3 (compound D8) (po, iv; 1, 3 mg/kg) exhibits excellent domestic pharmacokinetic properties [1]. PHGDH-IN-3 (ip; 12.5, 25, 50 mg/) kg; once a day for 31 consecutive days) exerts a significant anti-tumor effect in the PC9 xenograft mouse model [1].
In vivo, PHGDH-IN-3 is an orally active compound that can be used in cancer research. It has been investigated in preclinical models of cancers that are dependent on serine biosynthesis, such as certain breast cancers and melanomas with PHGDH amplification. The compound's oral bioavailability enables convenient dosing for efficacy studies. |
| Enzyme Assay |
The enzymatic activity of PHGDH-IN-3 is assessed using recombinant human PHGDH enzyme. The enzyme is incubated with the substrate 3-phosphoglycerate and NAD⁺ in the presence of varying concentrations of the test compound. The production of NADH is monitored spectrophotometrically at 340 nm. IC50 values are calculated from dose-response curves.
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| Cell Assay |
In vitro cellular assays for PHGDH-IN-3 are performed using cancer cell lines with PHGDH amplification or dependence on serine synthesis (e.g., MDA-MB-468 breast cancer cells). Cells are treated with the compound for 48-72 hours. Cell viability is measured using MTT or CellTiter-Glo assays. Serine and nucleotide levels in treated cells are quantified by LC-MS to confirm target engagement and pathway inhibition.
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| Animal Protocol |
Animal/Disease Models: ICR mouse[1]
Doses: 1, 3 mg/kg Route of Administration: Oral (po) and intravenous (iv) (iv)(iv) Administration Experimental Results: PK parameters iv (1 mg/kg) po (3 mg/kg ) AUC (h·ng/mL) 38,358 ± 14,768 94,386 ± 23,416 T1/2(h) 4.94 ± 0.38 4.74 ± 0.30 Tmax (h) 3.33 ± 1.15 CL_obs(mL/min/kg) 0.48 ± 0.23 Cmax(ng/mL ) 8842 ± 1755 F (%) 82.0 Animal/Disease Models: Balb/c nude mice [1] Doses: 12.5, 25, 50 mg/kg Route of Administration: intraperitoneal; one time/day for 31 days Experimental Results: Demonstrated It has anti-tumor effects in vivo and Dramatically delays tumor growth. 25 mg/kg Dramatically diminished tumor weight in mice. In vivo studies of PHGDH-IN-3 are conducted in xenograft mouse models of PHGDH-amplified cancers. The compound is administered orally at various doses. Tumor volumes are measured at regular intervals. Pharmacodynamic markers such as tumor serine levels and nucleotide synthesis rates are assessed. Body weight and overall health are monitored for tolerability. |
| ADME/Pharmacokinetics |
Pharmacokinetic properties of PHGDH-IN-3 are evaluated in rodents following oral and intravenous administration. Plasma concentrations are measured using LC-MS/MS to determine key parameters including oral bioavailability, half-life (t₁/₂), maximum concentration (Cmax), and area under the curve (AUC). The compound's oral bioavailability supports its use in in vivo efficacy studies.
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| Toxicity/Toxicokinetics |
PHGDH-IN-3 is intended for research use only and is not approved for clinical use. Standard toxicology assessments would include acute and repeat-dose toxicity studies in rodents, as well as safety pharmacology evaluations. No specific toxicity data is available in the public domain for this compound.
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| References | |
| Additional Infomation |
PHGDH-IN-3 is a research tool for studying cancer metabolism and the role of serine biosynthesis in tumor cell proliferation. Many cancers, particularly those with PHGDH amplification, are dependent on de novo serine synthesis for nucleotide production and cell growth. PHGDH inhibitors are being investigated as potential therapeutic agents for targeting metabolic vulnerabilities in cancer.
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| Molecular Formula |
C24H18FN3O4S2
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|---|---|
| Molecular Weight |
495.545826435089
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| Exact Mass |
495.07
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| Elemental Analysis |
C, 58.17; H, 3.66; F, 3.83; N, 8.48; O, 12.91; S, 12.94
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| CAS # |
2893778-31-7
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| PubChem CID |
166638116
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| Appearance |
Off-white to light brown solid powder
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| LogP |
4.1
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
8
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| Rotatable Bond Count |
7
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| Heavy Atom Count |
34
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| Complexity |
829
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C(NC1=NC(C2=CC=CC(F)=C2)=CS1)(=O)C1=CC=C(S(NC2=CC=CC(C(C)=O)=C2)(=O)=O)C=C1
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| InChi Key |
VUAMLKVINZWIJR-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C24H18FN3O4S2/c1-15(29)17-4-3-7-20(13-17)28-34(31,32)21-10-8-16(9-11-21)23(30)27-24-26-22(14-33-24)18-5-2-6-19(25)12-18/h2-14,28H,1H3,(H,26,27,30)
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| Chemical Name |
4-(N-(3-acetylphenyl)sulfamoyl)-N-(4-(3-fluorophenyl)thiazol-2-yl)benzamide
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| Synonyms |
PHGDH inhibitor D8; PHGDH-IN-D8; GLXC-26715; PHGDH-IN-3
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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 : ~100 mg/mL (~201.80 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 5 mg/mL (10.09 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 50.0 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 | 2.0180 mL | 10.0898 mL | 20.1796 mL | |
| 5 mM | 0.4036 mL | 2.0180 mL | 4.0359 mL | |
| 10 mM | 0.2018 mL | 1.0090 mL | 2.0180 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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