Narazaciclib| CAS# 1357470-29-1 | CDK inhibitor

MedKoo Cat#: 206460 | Name: Narazaciclib

Description:

WARNING: This product is for research use only, not for human or veterinary use.

Narazaciclib, also known as 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.

Chemical Structure

Narazaciclib

CAS#1357470-29-1

Theoretical Analysis

MedKoo Cat#: 206460

Name: Narazaciclib

CAS#: 1357470-29-1

Chemical Formula: C24H27N7O

Exact Mass: 429.2277

Molecular Weight: 429.53

Elemental Analysis: C, 67.11; H, 6.34; N, 22.83; O, 3.72

Price and Availability

Size	Price	Availability
10mg	USD 150.00	2 Weeks
25mg	USD 250.00	2 Weeks
50mg	USD 450.00	2 Weeks
100mg	USD 750.00	2 Weeks
200mg	USD 1,250.00	2 Weeks
500mg	USD 1,950.00	2 Weeks

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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

More Info

Product Data

Product Data

Instruction

View handling instruction

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	mg/mL	mM
Solubility
	DMF	16.0	37.25
	DMF:PBS (pH 7.2) (1:2)	0.3	0.70
	DMSO	18.6	43.20
	Ethanol	0.3	0.58

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 429.53 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:

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.