TH7299
TH7299 is a TbFolD inhibitor with antiparasitic activity. TH7299 binds the tetrahydrofolate-binding pocket of MTHFD2, and inhibits MTHFD2L and the dehydrogenase/cyclohydrolase domain of MTHFD1. TH7299 reduces cancer cells viability, induces apoptosis, DNA damage. TH7299 can be used for the researches of african trypanosomiasis and acute myeloid leukemia.
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- No. CAS: 1415648-20-2
- Fòrmula: C17H19N7O7
- Peso molecular:433.38
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Almacenamiento:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Actividad biológica
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Chemical Information
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Actividad biológica
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Cell Line
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Type | Value | Description | References |
|---|---|---|---|---|
| MOLM-14 | GI50 |
630 nM
Compound: Ly374571
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Growth inhibition of human MOLM-14 cells incubated for 72 hrs
Growth inhibition of human MOLM-14 cells incubated for 72 hrs
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[PMID: 39591507] |
| THP-1 | IC50 |
194 μM
Compound: 2
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Cytotoxicity against macrophages differentiated from human THP1 cells assessed as cell viability after 72 hrs by MTT assay
Cytotoxicity against macrophages differentiated from human THP1 cells assessed as cell viability after 72 hrs by MTT assay
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[PMID: 26322631] |
| THP-1 | IC50 |
49 μM
Compound: 2
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Antiparasitic activity against bloodstream form of Trypanosoma brucei brucei 427 infected in macrophages differentiated from human THP1 cells assessed as growth inhibition after 72 hrs by Alamar Blue assay
Antiparasitic activity against bloodstream form of Trypanosoma brucei brucei 427 infected in macrophages differentiated from human THP1 cells assessed as growth inhibition after 72 hrs by Alamar Blue assay
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[PMID: 26322631] |
TH7299 (Compound 2) (0-100 μM; 5 minutes) inhibits recombinant Trypanosoma brucei FolD dehydrogenase activity with a Ki of 1.1 ± 0.8 μM and an IC50 of 2.2 μM[1].
TH7299 (72 h) inhibits in vitro growth of bloodstream-form Trypanosoma brucei brucei with an IC50 of 49 ± 3.2 μM[1].
TH7299 potently inhibits the enzymatic activity of recombinant human MTHFD2 with an IC50 of 254 nM, and also inhibits the related folate enzymes MTHFD2L (IC50 = 126 nM)and MTHFD1-(DC) (IC50 = 89 nM)[2].
TH7299 (96 h) reduces the viability of HL-60 AML cells with an EC50 of 1110 nM[2].
TH7299 (30 μM; 2 h) engages with and stabilizes MTHFD2 in intact HL-60 AML cells[2].
TH7299 (10 μM; 24 h) reduces replication fork speed by ~50% in THP-1 AML cells, and this effect is completely rescued by co-treatment with 50 μM Thymidine (HY-N1150)[2].
TH7299 (3 μM; 24-48 h) induces time-dependent DNA damage (γH2AX positivity) primarily in S-phase and G2/M-phase HL-60 AML cells[2].
TH7299 (10-8-10-5 M; 96 h) dose-dependently induces late-stage apoptosis in HL-60 AML cells, with minimal apoptosis induction in nontumorigenic LCL-889 cells[2].
TH7299 (10-9-10-4 M; 96 h)-induced viability loss in HL-60 AML, THP-1 AML, and SW620 colorectal cancer cells is completely rescued by co-treatment with 50 μM Thymidine[2].
TH7299 (10 μM; 24 h) increases replication origin firing in THP-1 AML cells[2].
TH7299 (10 μM; 24 h) increases p-CHK1 and p-RPA32 levels in THP-1 cells[2].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:HL-60 AML cells, LCL-889 nontumorigenic lymphoblastoid cells
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Concentration:10-8-10-5 M
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Incubation Time:96 h
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Result:Induced late-stage apoptosis (annexin-V+/PI+) in ~60% of HL-60 cells at the highest concentration tested.
Induced late-stage apoptosis in <20% of LCL-889 cells at equivalent concentrations.
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Cell Line:HL-60 AML cells, THP-1 AML cells, SW620 colorectal cancer cells
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Concentration:10-9-10-4 M
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Incubation Time:96 h
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Result:Reduced viability of HL-60, THP-1, and SW620 cells, and this viability reduction was completely rescued by co-treatment with 50 μM Thymidine.
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Cell Line:THP-1 cells
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Concentration:10 μM
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Incubation Time:6， 24， 48, 72 h
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Result:Incresaed p-CHK1 and p-RPA32 levels at 24 h.
Increased p-CDK levels at 24 and 48 h.
Increased p21 levels at 48 and 72 h.
Increased γH2AX levels at 48 h.
Chemical Information
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No. CAS 1415648-20-2
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Peso molecular 433.38
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Fòrmula C17H19N7O7
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SMILES
N(C(NC1=CC=C(C(N[C@@H](CCC(O)=O)C(O)=O)=O)C=C1)=O)C2=C(N)NC(N)=NC2=O
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Envío
Room temperature in continental US; may vary elsewhere.
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Almacenamiento
Please store the product under the recommended conditions in the Certificate of Analysis.
Pureza y Documentación
Referencias
[1]. Eadsforth TC, et al. Characterization of 2,4-Diamino-6-oxo-1,6-dihydropyrimidin-5-yl Ureido Based Inhibitors of Trypanosoma brucei FolD and Testing for Antiparasitic Activity. J Med Chem. 2015;58(20):7938-7948. [Content Brief]
[2]. Bonagas N, et al. Pharmacological targeting of MTHFD2 suppresses acute myeloid leukemia by inducing thymidine depletion and replication stress. Nat Cancer. 2022;3(2):156-172. [Content Brief]
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
TH7299 Related Classifications
HY-148014 Related Classifications
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