AGI-24512 is a novel, potent and seletive MATA2 (methionine adenosyltransferase 2A) inhibitor with potential anticancer activities by blocking the growth of MTAP-deleted cancer cells in vitro. AGI-24512 also showed in vivo antitumor activity in MTAP null tumors.

Physicochemical Properties

Molecular Formula	C24H24N4O2
Molecular Weight	400.472965240479
Exact Mass	400.189
CAS #	2201066-53-5
PubChem CID	134307780
Appearance	White to gray solid powder
LogP	4.1
Hydrogen Bond Donor Count	2
Hydrogen Bond Acceptor Count	5
Rotatable Bond Count	3
Heavy Atom Count	30
Complexity	779
Defined Atom Stereocenter Count	0
SMILES	O=C1C(C2C=CC(=CC=2)O)=C(C)N=C2C(=C(C3C=CC=CC=3)NN21)N1CCCCC1
InChi Key	JDHPOXNOROPDTE-UHFFFAOYSA-N
InChi Code	InChI=1S/C24H24N4O2/c1-16-20(17-10-12-19(29)13-11-17)24(30)28-23(25-16)22(27-14-6-3-7-15-27)21(26-28)18-8-4-2-5-9-18/h2,4-5,8-13,25,29H,3,6-7,14-15H2,1H3
Chemical Name	6-(4-hydroxyphenyl)-5-methyl-2-phenyl-3-(piperidin-1-yl)pyrazolo[1,5-a]pyrimidin-7(4H)-one
Synonyms	AGI-24512 AGI 24512 AGI24512.
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)

Biological Activity

ln Vitro	AGI-24512 (0-1 μM; 96 hours) suppresses the growth of HCT116 cancer cells with an IC50 of 100 nM by blocking MTAP (methylthioadenosine phosphorylase)[1]. AGI-24512 suppresses PRMT5-mediated SDMA labeling in MTAP-/- cells with an IC50 of 95 nM, hence dramatically increasing MTAP-/. In HCT116 MTAP cells, AGI-24512 induces SAM (SAM). With an IC50 of 100 nM, the levels of S-adenosylmethionine) drop in a dose-dependent way [2].
ln Vivo	AGI-24512 showed limited barrier absorption and inhibitory half-life in malignancies [2].
References	[1]. MAT2A Inhibition Blocks the Growth of MTAP-Deleted Cancer Cells by Reducing PRMT5-Dependent mRNA Splicing and Inducing DNA Damage. Cancer Cell. 2021 Feb 8;39(2):209-224.e11. [2]. Discovery of AG-270, a First-in-Class Oral MAT2A Inhibitor for the Treatment of Tumors with Homozygous MTAP Deletion. J Med Chem. 2021 Apr 22;64(8):4430-4449.

Solubility Data

Solubility (In Vitro)

DMSO : ~125 mg/mL (~312.13 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.08 mg/mL (5.19 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (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 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: 2.08 mg/mL (5.19 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 3: ≥ 2.08 mg/mL (5.19 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 20.8 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	2.4971 mL	12.4853 mL	24.9707 mL
	5 mM	0.4994 mL	2.4971 mL	4.9941 mL
	10 mM	0.2497 mL	1.2485 mL	2.4971 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.