Cat. No.: HY-12624

Narazaciclib

(Synonyms: ON123300)

2 Cited Publications

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Based on 2 publication(s) in Google Scholar

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). Single agent Narazaciclib causes a dose-dependent suppression of phosphorylation of Akt as well as activation of Erk in brain tumors. Narazaciclib inhibits CDK6 with an IC₅₀ of 9.82 nM.

For research use only. We do not sell to patients.

Purity: 98.66%
CAS No.: 1357470-29-1
Formula: C₂₄H₂₇N₇O
Molecular Weight:429.52

Storage:

Powder -20°C, 3 years , 4°C, 2 years ; In solvent -80°C, 6 months , -20°C, 1 month

Narazaciclib Chemical Structure

CAS No.: 1357470-29-1

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Biological Activity
- Description
- IC₅₀ & Target
- Cellular Effect
- In Vitro
- In Vivo
- Clinical Trial
Chemical Information
Publications (2)
Solvent & Solubility
- In Vitro
- In Vivo
Purity & Documentation
References
Help & FAQs
Bioz

Biological Activity

Description

Narazaciclib (ON123300), a strong and brain-penetrant^[1] 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). Single agent Narazaciclib causes a dose-dependent suppression of phosphorylation of Akt as well as activation of Erk in brain tumors^[2]. Narazaciclib inhibits CDK6 with an IC₅₀ of 9.82 nM^[3].

IC₅₀ & Target^[2]^[3]

Cdk4/cyclin D1

3.9 nM (IC₅₀)

ARK5

5 nM (IC₅₀)

CDK6/cyclinD1

9.82 nM (IC₅₀)

RET

9.2 nM (IC₅₀)

FYN

11 nM (IC₅₀)

FGFR1

26 nM (IC₅₀)

PDGFRβ

26 nM (IC₅₀)

PI3K-δ

144 nM (IC₅₀)

All CDK Isoforms :

All AMPK Isoforms :

All PDGFR Isoforms :

Cellular Effect

Cell Line	Type	Value	Description	References
2008	GI₅₀	1.5 μM Compound: 7x	Cytotoxicity against human 2008 cells after 96 hrs by Cell-Titer Blue assay Cytotoxicity against human 2008 cells after 96 hrs by Cell-Titer Blue assay	[PMID: 24417566]
A-431	GI₅₀	0.25 μM Compound: 7x	Cytotoxicity against human A431 cells after 96 hrs by Cell-Titer Blue assay Cytotoxicity against human A431 cells after 96 hrs by Cell-Titer Blue assay	[PMID: 24417566]
A549	GI₅₀	0.2 μM Compound: 7x	Cytotoxicity against human A549 cells after 96 hrs by Cell-Titer Blue assay Cytotoxicity against human A549 cells after 96 hrs by Cell-Titer Blue assay	[PMID: 24417566]
BT-20	GI₅₀	0.1 μM Compound: 7x	Cytotoxicity against human BT20 cells after 96 hrs by Cell-Titer Blue assay Cytotoxicity against human BT20 cells after 96 hrs by Cell-Titer Blue assay	[PMID: 24417566]
BT-474	GI₅₀	0.25 μM Compound: 7x	Cytotoxicity against human BT474 cells after 96 hrs by Cell-Titer Blue assay Cytotoxicity against human BT474 cells after 96 hrs by Cell-Titer Blue assay	[PMID: 24417566]
CAPAN-1	GI₅₀	0.5 μM Compound: 7x	Cytotoxicity against human Capan1 cells after 96 hrs by Cell-Titer Blue assay Cytotoxicity against human Capan1 cells after 96 hrs by Cell-Titer Blue assay	[PMID: 24417566]
COLO 205	GI₅₀	0.1 μM Compound: 7x	Cytotoxicity against human COLO205 cells after 96 hrs by Cell-Titer Blue assay Cytotoxicity against human COLO205 cells after 96 hrs by Cell-Titer Blue assay	[PMID: 24417566]
DLD-1	GI₅₀	0.1 μM Compound: 7x	Cytotoxicity against human DLD1 cells after 96 hrs by Cell-Titer Blue assay Cytotoxicity against human DLD1 cells after 96 hrs by Cell-Titer Blue assay	[PMID: 24417566]
DU-145	GI₅₀	0.05 μM Compound: 7x	Cytotoxicity against human DU145 cells after 96 hrs by Cell-Titer Blue assay Cytotoxicity against human DU145 cells after 96 hrs by Cell-Titer Blue assay	[PMID: 24417566]
DU-145	IC₅₀	0.025 μM Compound: 7x	Cytotoxicity against human DU145 cells after 96 hrs by Cell-Titer Blue assay Cytotoxicity against human DU145 cells after 96 hrs by Cell-Titer Blue assay	[PMID: 24417566]
Granta-519	GI₅₀	0.025 μM Compound: 7x	Cytotoxicity against human GRANTA-519 cells after 96 hrs by Cell-Titer Blue assay Cytotoxicity against human GRANTA-519 cells after 96 hrs by Cell-Titer Blue assay	[PMID: 24417566]
HCC70	GI₅₀	1.5 μM Compound: 7x	Cytotoxicity against human HCC70 cells after 96 hrs by Cell-Titer Blue assay Cytotoxicity against human HCC70 cells after 96 hrs by Cell-Titer Blue assay	[PMID: 24417566]
HCT-15	GI₅₀	0.3 μM Compound: 7x	Cytotoxicity against human HCT15 cells after 96 hrs by Cell-Titer Blue assay Cytotoxicity against human HCT15 cells after 96 hrs by Cell-Titer Blue assay	[PMID: 24417566]
HeLa	GI₅₀	0.75 μM Compound: 7x	Cytotoxicity against human HeLa cells after 96 hrs by Cell-Titer Blue assay Cytotoxicity against human HeLa cells after 96 hrs by Cell-Titer Blue assay	[PMID: 24417566]
Jurkat	GI₅₀	0.15 μM Compound: 7x	Cytotoxicity against human Jurkat cells after 96 hrs by Cell-Titer Blue assay Cytotoxicity against human Jurkat cells after 96 hrs by Cell-Titer Blue assay	[PMID: 24417566]
K562	GI₅₀	0.1 μM Compound: 7x	Cytotoxicity against human K562 cells after 96 hrs by Cell-Titer Blue assay Cytotoxicity against human K562 cells after 96 hrs by Cell-Titer Blue assay	[PMID: 24417566]
K562	IC₅₀	0.05 μM Compound: 7x	Cytotoxicity against human K562 cells after 96 hrs by Cell-Titer Blue assay Cytotoxicity against human K562 cells after 96 hrs by Cell-Titer Blue assay	[PMID: 24417566]
MCF7	GI₅₀	0.15 μM Compound: 7x	Cytotoxicity against human MCF7 cells after 96 hrs by Cell-Titer Blue assay Cytotoxicity against human MCF7 cells after 96 hrs by Cell-Titer Blue assay	[PMID: 24417566]
MDA-MB-157	GI₅₀	1 μM Compound: 7x	Cytotoxicity against human MDA-MB-157 cells after 96 hrs by Cell-Titer Blue assay Cytotoxicity against human MDA-MB-157 cells after 96 hrs by Cell-Titer Blue assay	[PMID: 24417566]
MDA-MB-231	GI₅₀	0.25 μM Compound: 7x	Cytotoxicity against human MDA-MB-231 cells after 96 hrs by Cell-Titer Blue assay Cytotoxicity against human MDA-MB-231 cells after 96 hrs by Cell-Titer Blue assay	[PMID: 24417566]
MDA-MB-468	GI₅₀	2 μM Compound: 7x	Cytotoxicity against human MDA-MB-468 cells after 96 hrs by Cell-Titer Blue assay Cytotoxicity against human MDA-MB-468 cells after 96 hrs by Cell-Titer Blue assay	[PMID: 24417566]
MES-SA	GI₅₀	0.25 μM Compound: 7x	Cytotoxicity against human MES-SA cells after 96 hrs by Cell-Titer Blue assay Cytotoxicity against human MES-SA cells after 96 hrs by Cell-Titer Blue assay	[PMID: 24417566]
MES-SA/Dx5	GI₅₀	0.25 μM Compound: 7x	Cytotoxicity against human MES-SA/Dx5 cells after 96 hrs by Cell-Titer Blue assay Cytotoxicity against human MES-SA/Dx5 cells after 96 hrs by Cell-Titer Blue assay	[PMID: 24417566]
MIA PaCa-2	GI₅₀	0.25 μM Compound: 7x	Cytotoxicity against human MIAPaCa2 cells after 96 hrs by Cell-Titer Blue assay Cytotoxicity against human MIAPaCa2 cells after 96 hrs by Cell-Titer Blue assay	[PMID: 24417566]
NCI-H417	GI₅₀	0.25 μM Compound: 7x	Cytotoxicity against human NCI-N417 cells after 96 hrs by Cell-Titer Blue assay Cytotoxicity against human NCI-N417 cells after 96 hrs by Cell-Titer Blue assay	[PMID: 24417566]
NCI-N87	GI₅₀	0.9 μM Compound: 7x	Cytotoxicity against human NCI-N87 cells after 96 hrs by Cell-Titer Blue assay Cytotoxicity against human NCI-N87 cells after 96 hrs by Cell-Titer Blue assay	[PMID: 24417566]
Raji	GI₅₀	0.25 μM Compound: 7x	Cytotoxicity against human Raji cells after 96 hrs by Cell-Titer Blue assay Cytotoxicity against human Raji cells after 96 hrs by Cell-Titer Blue assay	[PMID: 24417566]
Sf9	IC₅₀	0.018 μM Compound: ON123300	Inhibition of GST-tagged CDK4/cyclin D1 (unknown origin) expressed in Baculovirus infected Sf9 cells using RPPTLSPIPHIPR peptide as substrate in presence of [gamma-33P]-ATP by radiometric filter binding assay Inhibition of GST-tagged CDK4/cyclin D1 (unknown origin) expressed in Baculovirus infected Sf9 cells using RPPTLSPIPHIPR peptide as substrate in presence of [gamma-33P]-ATP by radiometric filter binding assay	[PMID: 30234987]
Sf9	IC₅₀	0.117 μM Compound: ON123300	Inhibition of GST-tagged CDK9/CyclinT1 (unknown origin) expressed in Baculovirus infected Sf9 cells using YSPTSPS-2 KK peptide as substrate as substrate in presence of [gamma-33P]-ATP by radiometric filter binding assay Inhibition of GST-tagged CDK9/CyclinT1 (unknown origin) expressed in Baculovirus infected Sf9 cells using YSPTSPS-2 KK peptide as substrate as substrate in presence of [gamma-33P]-ATP by radiometric filter binding assay	[PMID: 30234987]
Sf9	IC₅₀	0.272 μM Compound: ON123300	Inhibition of GST-tagged CDK5/p25 (unknown origin) expressed in Baculovirus infected Sf9 cells using histone H1 as substrate as substrate in presence of [gamma-33P]-ATP by radiometric filter binding assay Inhibition of GST-tagged CDK5/p25 (unknown origin) expressed in Baculovirus infected Sf9 cells using histone H1 as substrate as substrate in presence of [gamma-33P]-ATP by radiometric filter binding assay	[PMID: 30234987]
Sf9	IC₅₀	0.377 μM Compound: ON123300	Inhibition of His-tagged CDK2/cyclin E (unknown origin) expressed in Baculovirus infected Sf9 cells using histone H1 as substrate in presence of [gamma-33P]-ATP by radiometric filter binding assay Inhibition of His-tagged CDK2/cyclin E (unknown origin) expressed in Baculovirus infected Sf9 cells using histone H1 as substrate in presence of [gamma-33P]-ATP by radiometric filter binding assay	[PMID: 30234987]
Sf9	IC₅₀	0.6 μM Compound: ON123300	Inhibition of His-tagged CDK1/cyclin B1 (unknown origin) expressed in Baculovirus infected Sf9 cells using histone H1 as substrate in presence of [gamma-33P]-ATP by radiometric filter binding assay Inhibition of His-tagged CDK1/cyclin B1 (unknown origin) expressed in Baculovirus infected Sf9 cells using histone H1 as substrate in presence of [gamma-33P]-ATP by radiometric filter binding assay	[PMID: 30234987]
Sf9	IC₅₀	6 μM Compound: ON123300	Inhibition of GST-tagged CDK7/cyclinH/MAT1 (unknown origin) expressed in Baculovirus infected Sf9 cells using YSPTSPS-2 KK peptide as substrate as substrate in presence of [gamma-33P]-ATP by radiometric filter binding assay Inhibition of GST-tagged CDK7/cyclinH/MAT1 (unknown origin) expressed in Baculovirus infected Sf9 cells using YSPTSPS-2 KK peptide as substrate as substrate in presence of [gamma-33P]-ATP by radiometric filter binding assay	[PMID: 30234987]
SK-BR-3	GI₅₀	0.15 μM Compound: 7x	Cytotoxicity against human SKBR3 cells after 96 hrs by Cell-Titer Blue assay Cytotoxicity against human SKBR3 cells after 96 hrs by Cell-Titer Blue assay	[PMID: 24417566]
SK-OV-3	GI₅₀	0.75 μM Compound: 7x	Cytotoxicity against human SKOV3 cells after 96 hrs by Cell-Titer Blue assay Cytotoxicity against human SKOV3 cells after 96 hrs by Cell-Titer Blue assay	[PMID: 24417566]
SNU-398	GI₅₀	0.2 μM Compound: 7x	Cytotoxicity against human SNU398 cells after 96 hrs by Cell-Titer Blue assay Cytotoxicity against human SNU398 cells after 96 hrs by Cell-Titer Blue assay	[PMID: 24417566]
SNU-449	GI₅₀	0.75 μM Compound: 7x	Cytotoxicity against human SNU449 cells after 96 hrs by Cell-Titer Blue assay Cytotoxicity against human SNU449 cells after 96 hrs by Cell-Titer Blue assay	[PMID: 24417566]
SNU-475	GI₅₀	0.3 μM Compound: 7x	Cytotoxicity against human SNU475 cells after 96 hrs by Cell-Titer Blue assay Cytotoxicity against human SNU475 cells after 96 hrs by Cell-Titer Blue assay	[PMID: 24417566]
SNU-5	GI₅₀	0.1 μM Compound: 7x	Cytotoxicity against human SNU5 cells after 96 hrs by Cell-Titer Blue assay Cytotoxicity against human SNU5 cells after 96 hrs by Cell-Titer Blue assay	[PMID: 24417566]
SW480	GI₅₀	0.09 μM Compound: 7x	Cytotoxicity against human SW480 cells after 96 hrs by Cell-Titer Blue assay Cytotoxicity against human SW480 cells after 96 hrs by Cell-Titer Blue assay	[PMID: 24417566]
U-266	GI₅₀	0.2 μM Compound: 7x	Cytotoxicity against human U266 cells after 96 hrs by Cell-Titer Blue assay Cytotoxicity against human U266 cells after 96 hrs by Cell-Titer Blue assay	[PMID: 24417566]
U-87MG ATCC	GI₅₀	0.1 μM Compound: 7x	Cytotoxicity against human U87 cells after 96 hrs by Cell-Titer Blue assay Cytotoxicity against human U87 cells after 96 hrs by Cell-Titer Blue assay	[PMID: 24417566]

In Vitro

Narazaciclib (ON123300) inhibits U87 glioma cell proliferation with an IC₅₀ of 3.4±0.1 μM^[2].? Narazaciclib (1 and 10 μM) inhibits cell proliferation in a panel of 11 glioma models including a patient-derived model (GBM10)^[2].
? Narazaciclib (6.3 μM; 1 h) reduces phosphorylation of Akt and its downstream signaling components, P70S6K, 40S rpS6 and Rb S780, yet ON123300 induces Erk activation in U87 cells; both in a dose- and time-dependent manner^[2].? ON123300 inhibits PI3Kδ with the IC₅₀ of 144nM^[3].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Cell Cytotoxicity Assay^[2]

Cell Line:

U87 glioma cells
Concentration:

0, 4, 8, 12, 16 μM
Incubation Time:

72 hour
Result:

Had an IC₅₀ equal to 3.4±0.1 μM.

Western Blot Analysis^[2]

Cell Line:

U87 cells
Concentration:

6.3 μM
Incubation Time:

1 h
Result:

Inhibited phosphorylation of Akt (at S473 site) and its downstream signaling components, P70S6K, 40S ribosomal protein S6 (rpS6) and Rb S780 (decreased to 40.1%; 31.8 %; 60.5%; 54.5% relatively to control), yet increased p-Erk (increased to 120% relative to control).

In Vivo

Narazaciclib (ON123300) decreases p-Akt expression and increases p-Erk activity in brain tumors upon administration at both IV doses of 5 mg/kg and 25 mg/kg in U87 brain tumor-bearing mouse. The half-life (T_1/2) is 1.5 h for 5 mg/kg and 25 mg/kg in plasma^[2].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Model:

NIH Swiss nude mice bearing U87 glioma model^[2].
Dosage:

5 mg/kg or 25 mg/kg
Administration:

IV bolus at a dose of either 5 mg/kg or 25 mg/kg via a tail vein.
Result:

The p-Akt rapidly declined and reached nadir values of 73% and 60% of control within 30 min after 5 mg/kg and 25 mg/kg dose levels, respectively.

Clinical Trial

NCT Number	Sponsor	Condition	Start Date	Phase A549
NCT01329991	Plexxikon\|		2011-05	PHASE1

Chemical Information

CAS No. 1357470-29-1
Appearance Solid
Molecular Weight 429.52
Formula C₂₄H₂₇N₇O
Color Yellow to orange
SMILES

N#CC1=CC2=CN=C(NC3=CC=C(N4CCN(C)CC4)C=C3)N=C2N(C5CCCC5)C1=O
Synonyms

ON123300
Shipping

Room temperature in continental US; may vary elsewhere.

Storage

Powder	-20°C	3 years
	4°C	2 years
In solvent	-80°C	6 months
	-20°C	1 month

Publications (2)

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Autophagy

An integrative multi-omics approach uncovers the regulatory role of CDK7 and CDK4 in autophagy activation induced by silica nanoparticles. [Abstract]

2021 Jun;17(6):1426-1447. PMID: 32397800
Department of Biochemistry

2020 Oct.

Solvent & Solubility

In Vitro:

DMSO : 16.67 mg/mL (38.81 mM; ultrasonic and warming and heat to 60°C; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)

View the Complete Stock Solution Preparation Table

Preparing Stock Solutions

View the Complete Stock Solution Preparation Table

Concentration Solvent Mass

1 mg

5 mg

10 mg

Concentration

Solvent

Mass

1 mM

2.3282 mL

11.6409 mL

23.2818 mL

5 mM

0.4656 mL

2.3282 mL

4.6564 mL

10 mM

0.2328 mL

1.1641 mL

2.3282 mL

Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.

Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.

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Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)

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In Vivo:

Working Solution

For the following dissolution methods, please prepare the working solution directly:

It is recommended to prepare fresh solutions and use them promptly within a short period of time.

The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.

Protocol 1

Add each solvent one by one: 0.5% CMC-Na/saline water

Solubility: 5 mg/mL (11.64 mM); Suspended solution; Need ultrasonic

Purity & Documentation

Select Batch:

Purity: 99.98%

Assay: 99.98%

ee.: 99.98%

Data Sheet (278 KB)
SDS (392 KB)
- English - EN (392 KB)
- Français - FR (392 KB)
- Deutsch - DE (392 KB)
- Norwegian - NO (392 KB)
- Español - ES (392 KB)
- Swedish - SV (392 KB)
- Italian - IT (392 KB)
- Portuguese - PT (392 KB)
COA (2659 KB)
Elemental Analysis Report (2659 KB)
HNMR (2659 KB)
CNMR (2659 KB)
RP-HPLC (2659 KB)
NP-HPLC (2659 KB)
MS (2659 KB)
LCMS (2659 KB)
IR (2659 KB)
GC (2659 KB)
OR (2659 KB)
SDS-PAGE (2659 KB)
SEC-HPLC (2659 KB)
Other Report (2659 KB)
Handling Instructions (2659 KB)

References

[1]. Hua Lv, et al. Integrated pharmacokinetic-driven approach to screen candidate anticancer drugs for brain tumor chemotherapy. AAPS J. 2013 Jan;15(1):250-7. [Content Brief]

[2]. Xiaoping Zhang, et al. Preclinical pharmacological evaluation of a novel multiple kinase inhibitor, ON123300, in brain tumor models. Mol Cancer Ther. 2014 May;13(5):1105-16. [Content Brief]

[3]. S K A Divakar, et al. 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. [Content Brief]

Help & FAQs

How should lyophilized recombinant proteins be reconstituted and stored?

1. Before opening the cap, centrifuge the vial at 13000 rpm for 20-30 seconds. This step will ensure that any lyophilized powder that may have adhered to the cap or walls is collected at the bottom of the vial, minimizing the risk of product loss.

Complete Stock Solution Preparation Table

Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.

Optional Solvent	Concentration Solvent Mass	1 mg	5 mg	10 mg	25 mg
DMSO	1 mM	2.3282 mL	11.6409 mL	23.2818 mL	58.2045 mL
	5 mM	0.4656 mL	2.3282 mL	4.6564 mL	11.6409 mL
	10 mM	0.2328 mL	1.1641 mL	2.3282 mL	5.8205 mL
	15 mM	0.1552 mL	0.7761 mL	1.5521 mL	3.8803 mL
	20 mM	0.1164 mL	0.5820 mL	1.1641 mL	2.9102 mL
	25 mM	0.0931 mL	0.4656 mL	0.9313 mL	2.3282 mL
	30 mM	0.0776 mL	0.3880 mL	0.7761 mL	1.9402 mL

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Narazaciclib

Cell Cycle/DNA Damage Compound Library

Epigenetics Compound Library

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PI3K/Akt/mTOR Compound Library

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Publications Citing Use of MedChemExpress (MCE) Narazaciclib

All CDK Isoforms

All AMPK Isoforms

All PDGFR Isoforms

Biological Activity

Chemical Information

Publications (2)

Solvent & Solubility

Purity & Documentation

References

Help & FAQs

Complete Stock Solution Preparation Table

Narazaciclib Related Classifications

Cat. No.: HY-12624