| Size | Price | Stock | Qty |
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| 5mg |
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| Targets |
APTO-253 targets multiple molecular pathways involved in cancer cell growth and survival. The compound is an inducer of KLF4 (Krüppel-like factor 4), a tumor suppressor that regulates cell proliferation, differentiation, and apoptosis. APTO-253 stabilizes G-quadruplex DNA structures, which are non-canonical DNA structures that form in guanine-rich regions of the genome. By stabilizing G-quadruplexes, APTO-253 reduces MYC mRNA expression and protein levels. The compound also induces CDKN1A (p21) expression, promoting G0-G1 cell cycle arrest. The combination of KLF4 induction, c-Myc inhibition, and G-quadruplex stabilization contributes to the anticancer activity of APTO-253.
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| 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].
In vitro, APTO-253 (5 μM) induces KLF4 expression in SKOV3 and OVCAR3 ovarian cancer cells. The compound enhances apoptosis induced by NSC 119875 in both cell lines. APTO-253 (5 μM) also leads to G1 phase arrest and reduces S and G2/M phase cells in SKOV3 and OVCAR3 cells. The compound induces cell cycle arrest and apoptosis in acute myeloid leukemia (AML) cells. APTO-253 inhibits c-Myc expression, which is a key oncogenic driver in many cancers. The compound demonstrates antiproliferative effects across a range of cancer cell lines. |
| ln Vivo |
APTO-253 (LOR-253; 15 mg/kg; intravenously; twice daily, 2 days a week for 14 days) shows anti-arthritic effects in a CIA model [3].
In vivo, APTO-253 has shown antitumor activity in preclinical models. The compound's ability to induce KLF4 expression and inhibit c-Myc makes it a promising candidate for the treatment of AML and other cancers. However, specific in vivo efficacy data, including tumor growth inhibition and survival studies, are not extensively detailed in the available literature. APTO-253's mechanism of action—targeting G-quadruplex DNA and modulating gene expression—represents a novel approach to cancer therapy. |
| Enzyme Assay |
APTO-253's stabilization of G-quadruplex DNA is assessed using biophysical techniques. Circular dichroism (CD) spectroscopy is used to monitor G-quadruplex formation and stabilization in the presence of APTO-253. Fluorescence resonance energy transfer (FRET) melting assays are used to measure the thermal stabilization of G-quadruplex structures. Electrophoretic mobility shift assays (EMSA) are used to assess the binding of APTO-253 to G-quadruplex DNA. These assays provide mechanistic insights into the interaction between APTO-253 and its DNA target.
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| Cell Assay |
APTO-253 is tested on cultured cancer cells, including AML cell lines and ovarian cancer cell lines (SKOV3, OVCAR3). Cells are treated with varying concentrations of APTO-253; KLF4 expression is assessed by qPCR and Western blot; MYC mRNA and protein levels are measured; cell cycle analysis is performed by flow cytometry; apoptosis is assessed by Annexin V staining or caspase activity assays; cell proliferation is measured by MTT or CellTiter-Glo assays. These cell-based assays demonstrate the mechanism of action and antiproliferative activity of APTO-253.
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| 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. APTO-253 has been evaluated in animal models of cancer. In preclinical studies, APTO-253 was tested in mouse xenograft models of AML and other cancers, demonstrating tumor growth inhibition. The compound's ability to induce KLF4 expression and inhibit c-Myc has been confirmed in vivo. Further studies are needed to fully characterize the in vivo efficacy and pharmacokinetic properties of APTO-253. |
| ADME/Pharmacokinetics |
Pharmacokinetic data for APTO-253 is limited in the available literature. As a small molecule, APTO-253 is expected to be orally bioavailable, but specific pharmacokinetic parameters such as half-life, Cmax, and bioavailability have not been extensively reported. The compound's conversion intracellularly from a monomer to a ferrous complex may influence its pharmacokinetic and pharmacodynamic properties.
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| Toxicity/Toxicokinetics |
The toxicity profile of APTO-253 is not extensively characterized in the available literature. The compound's mechanism of action—targeting G-quadruplex DNA and modulating gene expression—may have effects on normal cells as well as cancer cells. Comprehensive toxicological studies are needed to evaluate the safety profile of APTO-253.
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| References |
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| Additional Infomation |
APTO-253 (LOR-253) is a small molecule inducer of KLF4 that stabilizes G-quadruplex DNA and reduces MYC expression. The compound induces cell cycle arrest and apoptosis in AML cells and other cancer cell lines. APTO-253 represents a promising candidate for the treatment of AML and other cancers, with a novel mechanism of action targeting G-quadruplex DNA and modulating gene expression. The compound has shown preclinical activity and is being evaluated for its potential in cancer therapy. APTO-253 is not approved as a therapeutic agent and is used for research purposes only.
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| Molecular Formula |
C22H14FN5
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| Molecular Weight |
367.3785
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| Exact Mass |
367.123
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| CAS # |
916151-99-0
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| 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);
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| PubChem CID |
11960271
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| Appearance |
Light yellow to yellow solid powder
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| Density |
1.5±0.1 g/cm3
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| Boiling Point |
718.8±70.0 °C at 760 mmHg
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| Flash Point |
388.5±35.7 °C
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| Vapour Pressure |
0.0±2.3 mmHg at 25°C
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| Index of Refraction |
1.843
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| LogP |
3.33
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
1
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| Heavy Atom Count |
28
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| Complexity |
589
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| Defined Atom Stereocenter Count |
0
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| SMILES |
0
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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 |
| 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 : ~60 mg/mL (~163.32 mM)
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| 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.
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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