| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 50mg |
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| Targets |
APTO253 targets c-Myc, a key oncogene, by inhibiting its expression. It also stabilizes G-quadruplex DNA structures. It induces the expression of KLF4, a tumor suppressor. It promotes G0-G1 cell-cycle arrest and triggers apoptosis in AML cells without producing myelosuppression.
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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, APTO253 inhibits c-Myc expression and selectively induces CDKN1A (p21). It stabilizes G-quadruplex DNA, reduces MYC mRNA expression and protein levels. It induces DNA damage and triggers apoptosis in AML cells. These activities demonstrate its potent anti-leukemic effects. |
| 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].
In vivo, APTO253 has anti-arthritic activity and has been shown to be effective in various animal species without producing myelosuppression. Its ability to induce apoptosis in AML cells has been demonstrated in preclinical models. However, specific details of in vivo studies are not extensively detailed in the available literature. |
| Enzyme Assay |
The in vitro binding assay for APTO253 measures its ability to stabilize G-quadruplex DNA. These cell-free assays use techniques such as circular dichroism spectroscopy, fluorescence resonance energy transfer (FRET), or surface plasmon resonance (SPR) to assess the compound's interaction with G-quadruplex structures. Its effects on c-Myc expression are assessed in cellular assays.
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| Cell Assay |
In vitro cellular assays for APTO253 assess its effects on c-Myc expression and cell viability. AML cells are treated with APTO253, and c-Myc protein and mRNA levels are measured. Cell cycle analysis and apoptosis assays are performed to assess its anti-leukemic activity. These assays demonstrate the compound's functional activity in a relevant cellular context.
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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. In vivo animal studies for APTO253 have been conducted in models of AML to evaluate its antitumor efficacy. Its anti-arthritic activity has also been demonstrated. However, specific details of these studies are not extensively detailed in the available literature. It is a research compound and is not approved for clinical use. |
| ADME/Pharmacokinetics |
Specific pharmacokinetic data for APTO253 are not extensively detailed in the available literature. As a small molecule, its pharmacokinetic properties would be important for its in vivo efficacy. However, specific parameters such as half-life and bioavailability are not provided. It is intended for research use only.
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| Toxicity/Toxicokinetics |
Specific toxicity data for APTO253 are not extensively detailed in the available literature. A key feature of APTO253 is that it does not produce myelosuppression in various animal species and humans. This suggests a favorable safety profile compared to other anticancer agents. It is intended for research purposes only.
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| References |
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| Additional Infomation |
APTO253 is a small molecule that inhibits c-Myc expression and stabilizes G-quadruplex DNA. It induces cell cycle arrest and apoptosis in AML cells. It is a research compound with potential for the treatment of AML and other cancers. It is not approved for clinical use and is intended 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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| InChi Key |
NIRXBXIPHUTNNI-UHFFFAOYSA-N
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| 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)
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| Chemical Name |
2-(5-fluoro-2-methyl-1H-indol-3-yl)-1H-imidazo[4,5-f][1,10]phenanthroline
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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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