APTO-253 (LOR-253) is a small molecule that can inhibit c-Myc expression, stabilizes G-quadruplex DNA and induces cell cycle arrest and apoptosis in acute myeloid leukemia cells. APTO-253 mediates anti-cancer activity through induction of the Kruppel-like factor 4 (KLF4) tumor suppressor. APTO-253 has anti-arthritic activity.

Physicochemical Properties

Molecular Formula	C22H14FN5
Molecular Weight	367.3785
Exact Mass	367.123
CAS #	916151-99-0
Related CAS #	1691221-67-6 (HCl);916151-99-0 (Free base);1422731-37-0 (APTO-253 isomer HCl);1422826-80-9 (APTO-253 isomer free base);
PubChem CID	11960271
Appearance	Light yellow to yellow solid powder
Density	1.5±0.1 g/cm3
Boiling Point	718.8±70.0 °C at 760 mmHg
Flash Point	388.5±35.7 °C
Vapour Pressure	0.0±2.3 mmHg at 25°C
Index of Refraction	1.843
LogP	3.33
Hydrogen Bond Donor Count	2
Hydrogen Bond Acceptor Count	4
Rotatable Bond Count	1
Heavy Atom Count	28
Complexity	589
Defined Atom Stereocenter Count	0
SMILES	0
InChi Key	NIRXBXIPHUTNNI-UHFFFAOYSA-N
InChi Code	InChI=1S/C22H14FN5/c1-11-17(15-10-12(23)6-7-16(15)26-11)22-27-20-13-4-2-8-24-18(13)19-14(21(20)28-22)5-3-9-25-19/h2-10,26H,1H3,(H,27,28)
Chemical Name	2-(5-fluoro-2-methyl-1H-indol-3-yl)-1H-imidazo[4,5-f][1,10]phenanthroline
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	It is known that APTO-253 (LOR-253) induces KLF4. In SKOV3 and OVCAR3 cells, APTO-253 (5 μM) increases NSC 119875-induced apoptosis and increases KLF4 expression. In SKOV3 and OVCAR3 cells, APTO-253 (5 μM) similarly results in G1 arrest and decreases S and G2/M phase cells [1]. Raji and Raji/253R cell lines are cytotoxic to APTO-253, with IC50s of 105 ± 2.4 nM and 1387 ± 94 nM, respectively. In Raji cells, APTO-253 (0.5 μM) similarly damages DNA. Cells lacking BRCA1/2 exhibit hypersensitivity to APTO-253. Raji/253R's resistance to APTO-253 can be reversed by inhibiting ABCG2, as HEK-293 cells overexpressing ABCG2 are resistant to the drug [2]. AML and several types of lymphoma cell lines cannot proliferate when APTO-253 is present; its IC50 ranges from 57 nM to 1.75 µM. In AML lines, APTO-253 (500 nM) also triggers apoptosis, causes G0/G1 cell cycle arrest, and downregulates MYC RNA and protein expression. In MV4-11 cells, APTO-253 (500 nM) activates the DNA damage response mechanism. Furthermore, APTO-253 has the highest propensity to stabilize the MYC G4 sequence and is an efficient stabilizer of the Gquadruplex (G4) motif [3].
ln Vivo	APTO-253 (LOR-253; 15 mg/kg; intravenously administered twice daily, twice weekly for 14 days) exhibits anti-arthritic efficacy in a CIA model [3].
Animal Protocol	Animal/Disease Models: DBA/1J male mice with collagen-induced arthritis (CIA) (6 weeks) [3] Doses: 15 mg/kg Route of Administration: IV; twice (two times) daily for 2 days per week for 14 Experimental Results: It has significant preventive and therapeutic activity against arthritis formation.
References	[1]. APTO-253 Stabilizes G-quadruplex DNA, Inhibits MYC Expression, and Induces DNA Damage in Acute Myeloid Leukemia Cells. Mol Cancer Ther. 2018 Jun;17(6):1177-1186. [2]. Inhibition of c-Myc By Apto-253 As an Innovative Therapeutic Approach to Induce Cell Cycle Arrest and Apoptosis in Acute Myeloid Leukemia. Blood 2016 128:1716. [3]. Parsing multiomics landscape of activated synovial fibroblasts highlights drug targets linked to genetic risk of rheumatoid arthritis. Ann Rheum Dis. 2020 Nov2;annrheumdis-2020-218189.

Solubility Data

Solubility (In Vitro)

DMSO : ~60 mg/mL (~163.32 mM)

Solubility (In Vivo)

Solubility in Formulation 1: 2.3 mg/mL (6.26 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with heating and sonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 23.0 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 (5.66 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.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.7220 mL	13.6099 mL	27.2198 mL
	5 mM	0.5444 mL	2.7220 mL	5.4440 mL
	10 mM	0.2722 mL	1.3610 mL	2.7220 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.