AGF347
AGF347 is a one-carbon/purine biosynthesis inhibitor. AGF347 inhibits SHMT1/2 serine hydroxymethyltransferase and GARFTase/AICARFTase de novo purine formyltransferases, with target Ki values of 2.91 µM, 2.19 µM, 3.13 µM, and 3.72 µM, respectively. AGF347 depletes adenine nucleotides, inhibits mTOR/S6K1 signaling, reduces GSH/GSSG, and induces Apoptosis. AGF347 exhibits anticancer activity against lung cancer, colon cancer, pancreatic cancer, and epithelial ovarian cancer cells.
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- CAS No.: 2294820-23-6
- Formula: C22H24FN5O6
- Molecular Weight:473.45
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Storage:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Biological Activity
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Chemical Information
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- References
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Help & FAQs
Biological Activity
Description
IC50 & Target
[1]|
mTOR |
SHMT2 2.19 μM (Ki) |
SHMT1 2.91 μM (Ki) |
Cellular Effect
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Cell Line
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Type | Value | Description | References |
|---|---|---|---|---|
| HCT-116 | IC50 |
437 nM
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Antiproliferative activity against human HCT116 cells assessed as proliferation inhibition relative to vehicle-treated controls.
Antiproliferative activity against human HCT116 cells assessed as proliferation inhibition relative to vehicle-treated controls.
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31289137 |
| HCT-116 | IC50 |
42 nM
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Antiproliferative activity against human HCT116 SHMT2 knockout cells assessed as proliferation inhibition relative to vehicle-treated controls in glycine-supplemented media.
Antiproliferative activity against human HCT116 SHMT2 knockout cells assessed as proliferation inhibition relative to vehicle-treated controls in glycine-supplemented media.
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31289137 |
| NCI-H460 | IC50 |
214 nM
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Antiproliferative activity against human H460 cells assessed as dose-dependent growth inhibition relative to controls, with response modulated by adenosine and glycine supplementation.
Antiproliferative activity against human H460 cells assessed as dose-dependent growth inhibition relative to controls, with response modulated by adenosine and glycine supplementation.
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31289137 |
| MIA PaCa-2 | IC50 |
1381 nM
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Antiproliferative activity against human MIA PaCa-2 cells assessed as proliferation inhibition relative to vehicle-treated controls.
Antiproliferative activity against human MIA PaCa-2 cells assessed as proliferation inhibition relative to vehicle-treated controls.
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31289137 |
| HGC-27 | IC50 |
106.6 μM
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Inhibition of viability/proliferation in HGC-27 gastric cancer cells.
Inhibition of viability/proliferation in HGC-27 gastric cancer cells.
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40346149 |
In Vitro
AGF347 inhibits the proliferation of Cisplatin (HY-17394)-resistant SKOV3, TOV112D, and A2780 EOC cells in the nanomolar range, with PCFT and/or RFC together with FRα participating in uptake[4].
AGF347 accumulates abundantly in both the cytoplasm and mitochondria of IGROV1 EOC cells[4].
AGF347 shows in vitro antitumor activity in pancreatic cancer cell lines, including MIA PaCa-2, and FPGS transcript levels correlate with response[5].
AGF347 (0-5 µM; 96 hours) inhibits the proliferation of Cisplatin-sensitive and Cisplatin-resistant EOC cell lines, including SKOV3, A2780-E80, and CaOV3, with weaker activity against IOSE 7576 normal ovarian epithelial cells[6].
AGF347 (10 µM; 48 hours) reduces clonogenic survival of SKOV3 and A2780-E80 Cisplatin-resistant EOC cells[6].
AGF347 exhibits in vitro antitumor potency against H460, HCT-116, and MIA PaCa-2 cancer cells[8].
AGF347 accumulation in MIA PaCa-2 cells increases with FPGS levels of mFPGS#32 in the mitochondrial and cytosolic compartments, whereas cFPGS#3 increases accumulation only in the cytosol[5].
AGF347 directly inhibits purified SHMT2, SHMT1, GARFTase, and AICARFTase in cell-free assays[6].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:human epithelial ovarian cell lines IGROV1, SKOV3, CaOV3, A2780, and A2780-E80; normal ovarian epithelial IOSE 7576 cells
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Concentration:0-5 µM; folic acid 200 nM (parallel)
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Incubation Time:96 h
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Result:Inhibited proliferation across EOC cell lines, including cisplatin-resistant SKOV3 and A2780-E80 cells and CaOV3 HGS cells.
Inhibitory potency toward normal IOSE 7576 ovarian cells was modest.
Folic acid reversed the inhibitory effects to varying degrees, most pronounced in IGROV1 cells.
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Cell Line:SKOV3 cells
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Concentration:10 µM
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Incubation Time:48 h
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Result:Increased early apoptosis to 1.55% versus 0.77% in control cells and late apoptosis to 8.33% versus 3.54% in control cells.
In Vivo
AGF347 (14 mg/kg/dose; intravenous injection; once every 2 days; 8 doses total starting from day 3 after implantation) produces antitumor efficacy against Cisplatin-resistant SKOV3 ovarian cancer xenografts, with a tumor growth delay of 10 days and cell killing of 1.4 log[6].
AGF347 produces potent in vivo antitumor efficacy against MIA PaCa-2 pancreatic adenocarcinoma xenografts in SCID mice, with a median tumor growth delay of >38 days, and 1 of 5 mice is tumor-free 122 days after dosing[7].
AGF347 exhibits in vivo antitumor efficacy in SCID mice bearing SKOV3 EOC xenografts[9].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:NCr SCID (female; 11 weeks old; average body weight 20.2 g)[1]
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Dosage:15 mg/kg per injection, Q2dx8 (every other day × 8 injections), total dose 120 mg/kg
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Administration:Q2dx8 (every other day × 8 injections)
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Result:Individual-mouse tumor burden curves showed delayed tumor growth far beyond the untreated and gemcitabine groups, with tumor regression below the limit of palpation in some mice.
The observation period extended beyond 150 days post-implant, and a mouse was rechallenged at approximately that point.
Significant in vivo antitumor efficacy with potential for complete responses was reported against early-stage MIA PaCa-2 xenografts.
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Animal Model:ICR SCID (female; 10 weeks old; average body weight 19 g)[1]
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Dosage:15 mg/kg per injection, Q2dx8 (every other day × 8 injections), total dose 120 mg/kg
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Administration:Q2dx8 (every other day × 8 injections)
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Result:In the upstage trial, mice showed tumor growth delay/regression relative to the untreated and gemcitabine groups, with individual tumor burden curves extending to about 70 days post-implant and one mouse showing prolonged suppression.
In tumor samples from upstage-trial mice (normalized to controls set at 1.0), GAR and AICAR pools were markedly elevated.
AMP relative abundance increased and ADP and ATP relative abundance decreased in tumors; serine abundance was not significantly changed.
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Animal Model:NCr SCID (female)[6]
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Dosage:14 mg/kg/injection
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Administration:i.v.; every 2 days; for 8 doses starting day 3 post-implantation
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Result:Median tumor burden on day 24 was 564 mg.
T/C was 36%.
Tumor-free on day 38 was 0/7.
Time to 1000 mg was 31 days.
Tumor growth delay was 10 days.
Log cell kill was 1.4.
In a separate standard folate-replete diet arm, antitumor activity was completely ablated.
Chemical Information
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CAS No. 2294820-23-6
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Molecular Weight 473.45
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Formula C22H24FN5O6
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SMILES
FC(C=C1CCCCN2C3=C(NC(N)=NC3=O)C=C2)=C(C=C1)C(N[C@H](C(O)=O)CCC(O)=O)=O
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
Please store the product under the recommended conditions in the Certificate of Analysis.
Purity & Documentation
References
[1]. Dekhne AS, et al. Novel Pyrrolo[3,2-]pyrimidine Compounds Target Mitochondrial and Cytosolic One-carbon Metabolism with Broad-spectrum Antitumor Efficacy. Molecular cancer therapeutics. 2019 Oct;18(10):1787-1799. [Content Brief]
[2]. Dekhne AS, et al. Therapeutic Targeting of Mitochondrial One-Carbon Metabolism in Cancer. Molecular cancer therapeutics. 2020 Nov;19(11):2245-2255. [Content Brief]
[3]. Deng H, et al. SHMT inhibitor synergizes with 5-Fu to suppress gastric cancer via cell cycle arrest and chemoresistance alleviation. NPJ precision oncology. 2025 May 09;9(1):135. [Content Brief]
[4]. Wallace-Povirk AC, et al. Targeting mitochondrial and cytosolic one-carbon metabolism in epithelial ovarian cancer via folate receptor alpha. Cancer Research. 2021 Jul 1;81(13_Supplement):2348-. [Content Brief]
[6]. Wallace-Povirk A, et al. Mitochondrial and Cytosolic One-Carbon Metabolism Is a Targetable Metabolic Vulnerability in Cisplatin-Resistant Ovarian Cancer. Molecular cancer therapeutics. 2024 Jun 04;23(6):809-822. [Content Brief]
[9]. Wallace-Povirk A, et al. Folate transport and one-carbon metabolism in targeted therapies of epithelial ovarian cancer. Cancers. 2021 Dec 31;14(1):191. [Content Brief]
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
AGF347 Related Classifications
HY-177092 Related Classifications
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