WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 206460
CAS#: 1357470-29-1
Description: ON123300 is a potent multikinase inhibitor and may be potential useful for brain tumor chemotherapy. ON123300 strongly inhibits Ark5 and CDK4, as well as growth factor receptor tyrosine kinases such as β-type platelet-derived growth factor receptor (PDGFRβ). ON123300 inhibits U87 glioma cell proliferation with an IC(50) 3.4 ± 0.1 μmol/L. ON123300 exhibits potent activity against mantle cell lymphomas (MCLs) both in vitro and in vivo. ON123300 might be an effective agent in MCL, including ibrutinib-resistant forms of the disease.
MedKoo Cat#: 206460
Name: ON-123300
CAS#: 1357470-29-1
Chemical Formula: C24H27N7O
Exact Mass: 429.2277
Molecular Weight: 429.528
Elemental Analysis: C, 67.11; H, 6.34; N, 22.83; O, 3.72
Synonym: ON-123300; ON 123300; ON123300; Narazaciclib
IUPAC/Chemical Name: 8-cyclopentyl-2-((4-(4-methylpiperazin-1-yl)phenyl)amino)-7-oxo-7,8-dihydropyrido[2,3-d]pyrimidine-6-carbonitrile
InChi Key: VADOZMZXXRBXNY-UHFFFAOYSA-N
InChi Code: InChI=1S/C24H27N7O/c1-29-10-12-30(13-11-29)20-8-6-19(7-9-20)27-24-26-16-18-14-17(15-25)23(32)31(22(18)28-24)21-4-2-3-5-21/h6-9,14,16,21H,2-5,10-13H2,1H3,(H,26,27,28)
SMILES Code: N#CC1=CC2=CN=C(NC3=CC=C(N4CCN(C)CC4)C=C3)N=C2N(C5CCCC5)C1=O
Appearance: Solid powder
Purity: >98% (or refer to the Certificate of Analysis)
Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility: Soluble in DMSO, not in water
Shelf Life: >2 years if stored properly
Drug Formulation: This drug may be formulated in DMSO
Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code: 2934.99.9001
| Biological target: | Narazaciclib (ON123300), a strong and brain-penetrant multi-kinase inhibitor, inhibits CDK4 (IC50=3.9 nM), Ark5 (IC50=5 nM), PDGFRβ (IC50=26 nM), FGFR1 (IC50=26 nM), RET (IC50=9.2 nM), and FYN (IC50=11 nM). |
| In vitro activity: | Treatment of multiple myeloma cell lines and primary samples with ON123300 in vitro resulted in rapid induction of cell-cycle arrest followed by apoptosis. ON123300-mediated ARK5 inhibition or ARK5-specific siRNAs resulted in the inhibition of the mTOR/S6K pathway and upregulation of the AMPK kinase cascade. AMPK upregulation resulted in increased SIRT1 levels and destabilization of steady-state MYC protein. Reference: Cancer Res. 2016 Mar 1;76(5):1225-36. https://pubmed.ncbi.nlm.nih.gov/26873845/ |
| In vivo activity: | As seen here and in figure 6A, treatment with ON123300 significantly inhibited (p<0.05) tumor growth over a 2-week period, suggesting that this compound is a potent inhibitor of MCL proliferation in vivo. In addition, daily treatment with ON123300 did not cause a significant reduction in the total body weights of ON123300-treated mice (Fig 6C). (The increase in the body weights of the untreated animals is likely attributable to the rapid growth of tumors). Reference: Leukemia. 2016 Jan;30(1):86-93. https://pubmed.ncbi.nlm.nih.gov/26174628/ |
| Solvent | Max Conc. mg/mL | Max Conc. mM | |
|---|---|---|---|
| Solubility | |||
| DMF | 16.0 | 37.25 | |
| DMF:PBS (pH 7.2) (1:2) | 0.3 | 0.7 | |
| DMSO | 18.56 | 43.2 | |
| Ethanol | 0.25 | 0.58 |
The following data is based on the product molecular weight 429.528 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass | 1 mg | 5 mg | 10 mg |
|---|---|---|---|
| 1 mM | 1.15 mL | 5.76 mL | 11.51 mL |
| 5 mM | 0.23 mL | 1.15 mL | 2.3 mL |
| 10 mM | 0.12 mL | 0.58 mL | 1.15 mL |
| 50 mM | 0.02 mL | 0.12 mL | 0.23 mL |
| Formulation protocol: | 1. Perumal D, Kuo PY, Leshchenko VV, Jiang Z, Divakar SK, Cho HJ, Chari A, Brody J, Reddy MV, Zhang W, Reddy EP, Jagannath S, Parekh S. Dual Targeting of CDK4 and ARK5 Using a Novel Kinase Inhibitor ON123300 Exerts Potent Anticancer Activity against Multiple Myeloma. Cancer Res. 2016 Mar 1;76(5):1225-36. doi: 10.1158/0008-5472.CAN-15-2934. Epub 2016 Feb 12. PMID: 26873845; PMCID: PMC5968814. 2. Zhang X, Lv H, Zhou Q, Elkholi R, Chipuk JE, Reddy MV, Reddy EP, Gallo JM. Preclinical pharmacological evaluation of a novel multiple kinase inhibitor, ON123300, in brain tumor models. Mol Cancer Ther. 2014 May;13(5):1105-16. doi: 10.1158/1535-7163.MCT-13-0847. Epub 2014 Feb 25. PMID: 24568969; PMCID: PMC4013241. 3.Divakar SK, Ramana Reddy MV, Cosenza SC, Baker SJ, Perumal D, Antonelli AC, Brody J, Akula B, Parekh S, Reddy EP. Dual inhibition of CDK4/Rb and PI3K/AKT/mTOR pathways by ON123300 induces synthetic lethality in mantle cell lymphomas. Leukemia. 2016 Jan;30(1):86-93. doi: 10.1038/leu.2015.185. Epub 2015 Jul 15. PMID: 26174628; PMCID: PMC4703501. |
| In vitro protocol: | 1. Perumal D, Kuo PY, Leshchenko VV, Jiang Z, Divakar SK, Cho HJ, Chari A, Brody J, Reddy MV, Zhang W, Reddy EP, Jagannath S, Parekh S. Dual Targeting of CDK4 and ARK5 Using a Novel Kinase Inhibitor ON123300 Exerts Potent Anticancer Activity against Multiple Myeloma. Cancer Res. 2016 Mar 1;76(5):1225-36. doi: 10.1158/0008-5472.CAN-15-2934. Epub 2016 Feb 12. PMID: 26873845; PMCID: PMC5968814. 2. Zhang X, Lv H, Zhou Q, Elkholi R, Chipuk JE, Reddy MV, Reddy EP, Gallo JM. Preclinical pharmacological evaluation of a novel multiple kinase inhibitor, ON123300, in brain tumor models. Mol Cancer Ther. 2014 May;13(5):1105-16. doi: 10.1158/1535-7163.MCT-13-0847. Epub 2014 Feb 25. PMID: 24568969; PMCID: PMC4013241. |
| In vivo protocol: | 1. Divakar SK, Ramana Reddy MV, Cosenza SC, Baker SJ, Perumal D, Antonelli AC, Brody J, Akula B, Parekh S, Reddy EP. Dual inhibition of CDK4/Rb and PI3K/AKT/mTOR pathways by ON123300 induces synthetic lethality in mantle cell lymphomas. Leukemia. 2016 Jan;30(1):86-93. doi: 10.1038/leu.2015.185. Epub 2015 Jul 15. PMID: 26174628; PMCID: PMC4703501. 2. Zhang X, Lv H, Zhou Q, Elkholi R, Chipuk JE, Reddy MV, Reddy EP, Gallo JM. Preclinical pharmacological evaluation of a novel multiple kinase inhibitor, ON123300, in brain tumor models. Mol Cancer Ther. 2014 May;13(5):1105-16. doi: 10.1158/1535-7163.MCT-13-0847. Epub 2014 Feb 25. PMID: 24568969; PMCID: PMC4013241. |
1: Divakar SK, Ramana Reddy MV, Cosenza SC, Baker SJ, Perumal D, Antonelli AC, Brody J, Akula B, Parekh S, Premkumar Reddy E. Dual inhibition of CDK4/Rb and PI3K/AKT/mTOR pathways by ON123300 induces synthetic lethality in mantle cell lymphomas. Leukemia. 2015 Jul 15. doi: 10.1038/leu.2015.185. [Epub ahead of print] PubMed PMID: 26174628.
2: Zhang X, Lv H, Zhou Q, Elkholi R, Chipuk JE, Reddy MV, Reddy EP, Gallo JM. Preclinical pharmacological evaluation of a novel multiple kinase inhibitor, ON123300, in brain tumor models. Mol Cancer Ther. 2014 May;13(5):1105-16. doi: 10.1158/1535-7163.MCT-13-0847. Epub 2014 Feb 25. PubMed PMID: 24568969; PubMed Central PMCID: PMC4013241.
3: Lv H, Zhang X, Sharma J, Reddy MV, Reddy EP, Gallo JM. Integrated pharmacokinetic-driven approach to screen candidate anticancer drugs for brain tumor chemotherapy. AAPS J. 2013 Jan;15(1):250-7. doi: 10.1208/s12248-012-9428-4. Epub 2012 Nov 22. PubMed PMID: 23180160; PubMed Central PMCID: PMC3535101.
