AZ191 | CAS#1594092-37-1 | DYRK1B inhibitor

MedKoo Cat#: 407155 | Name: AZ191

Description:

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

AZ191 is a novel, potent and selective DYRK1B inhibitor. AZ191 demonstrates that DYRK1B acts independently of GSK3β to phosphorylate cyclin D1 at Thr(286), not Thr(288). AZ191 selectively inhibits DYRK1B in vitro and in cells. DYRK1B (dual-specificity tyrosine phosphorylation-regulated kinase 1B) is amplified in certain cancers and may be an oncogene. AZ191 may prove useful in defining further substrates and biological functions of DYRK1B.

Chemical Structure

AZ191

CAS#1594092-37-1

Theoretical Analysis

MedKoo Cat#: 407155

Name: AZ191

CAS#: 1594092-37-1

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 90.00	Ready to ship
25mg	USD 150.00	Ready to ship
50mg	USD 250.00	Ready to ship
100mg	USD 450.00	Ready to ship
200mg	USD 850.00	Ready to ship
500mg	USD 1,850.00	Ready to ship
1g	USD 2,950.00	Ready to ship
2g	USD 4,650.00	2 Weeks

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Synonym

AZ191; AZ-191; AZ 191.

IUPAC/Chemical Name

N-(2-methoxy-4-(4-methylpiperazin-1-yl)phenyl)-4-(1-methyl-1H-pyrrolo[2,3-c]pyridin-3-yl)pyrimidin-2-amine

InChi Key

ZYVXTMKTGDARKR-UHFFFAOYSA-N

InChi Code

InChI=1S/C24H27N7O/c1-29-10-12-31(13-11-29)17-4-5-21(23(14-17)32-3)28-24-26-9-7-20(27-24)19-16-30(2)22-15-25-8-6-18(19)22/h4-9,14-16H,10-13H2,1-3H3,(H,26,27,28)

SMILES Code

CN1C=C(C2=NC(NC3=CC=C(N4CCN(C)CC4)C=C3OC)=NC=C2)C5=C1C=NC=C5

Appearance

Brown 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

Certificate of Analysis

View CoA: current batch, Lot#CRB61102

QC Data

View QC data: current batch, Lot#CRB61102

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

Biological target:

AZ191 is an inhibitor that selectively inhibits DYRK1B with IC50 of 17 nM.

In vitro activity:

In contrast, in THP-1 cells differentiated to macrophages by PMA, AZ191 induced a M1-like pro-inflammatory cytokine release pattern similar to MBZ and LPS/IFNγ (Fig. 2c–f). MBZ (Fig. 2e), LPS/IFNγ (Fig. 2c) and AZ191 (Fig. 2f) clearly increased both IL1β and TNF (tumour necrosis factor) and decreased VEGF (vascular endothelial growth factor) opposite to the effect of M2 inducing IL13/IL4 stimulation (Fig. 2d). In repeat experiments with IL1β and TNF the effect of AZ191 was statistically significant compared to DMSO control (P < 0.01, n = 4, paired Students t-test). Moreover, AZ191 increased the expression of the M1 marker CD80 and decreased the M2 marker CD163 in the THP-1 macrophage model (Fig. 3a with the original flow cytometry histograms shown in Additional file 2: Fig. S2), corroborating previously published results for MBZ. Reference: BMC Res Notes. 2019; 12: 234. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6477744/

In vivo activity:

To explore the targeted therapeutic potential of DYRK1 in HCC cells with upregulated TROAP, AZ191 was used to treat the subcutaneous xenograft tumors derived from Hep3B or PLC8024 cells in nude mice. Compared to DMSO treatment, tumor growth was significantly suppressed after six times injection of AZ191 (50 mg/kg, i.p.) (Fig. 6A). IHC staining also confirmed the lower percentage of Ki67 positive cells in xenograft tumors treated with AZ191 (Fig. 6B). Reference: Cell Death Dis. 2021 Jan; 12(1): 125. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7838256/

	Solvent	mg/mL	mM
Solubility
	DMSO	40.2	96.68
	DMF	2.0	4.66
	Ethanol	3.9	8.99
	Ethanol:PBS (pH 7.2) (1:1)	0.5	1.16

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. Blom K, Rubin J, Berglund M, Jarvius M, Lenhammar L, Parrow V, Andersson C, Loskog A, Fryknäs M, Nygren P, Larsson R. Mebendazole-induced M1 polarisation of THP-1 macrophages may involve DYRK1B inhibition. BMC Res Notes. 2019 Apr 22;12(1):234. doi: 10.1186/s13104-019-4273-5. PMID: 31010428; PMCID: PMC6477744. 3. Chen H, Shen J, Choy E, Hornicek FJ, Shan A, Duan Z. Targeting DYRK1B suppresses the proliferation and migration of liposarcoma cells. Oncotarget. 2017 Nov 28;9(17):13154-13166. doi: 10.18632/oncotarget.22743. PMID: 29568347; PMCID: PMC5862568. 1. Li L, Wei JR, Song Y, Fang S, Du Y, Li Z, Zeng TT, Zhu YH, Li Y, Guan XY. TROAP switches DYRK1 activity to drive hepatocellular carcinoma progression. Cell Death Dis. 2021 Jan 26;12(1):125. doi: 10.1038/s41419-021-03422-3. PMID: 33500384; PMCID: PMC7838256.

In vitro protocol:

In vivo protocol:

1. Li L, Wei JR, Song Y, Fang S, Du Y, Li Z, Zeng TT, Zhu YH, Li Y, Guan XY. TROAP switches DYRK1 activity to drive hepatocellular carcinoma progression. Cell Death Dis. 2021 Jan 26;12(1):125. doi: 10.1038/s41419-021-03422-3. PMID: 33500384; PMCID: PMC7838256.

1: Ashford AL, Oxley D, Kettle J, Hudson K, Guichard S, Cook SJ, Lochhead PA. A novel DYRK1B inhibitor AZ191 demonstrates that DYRK1B acts independently of GSK3β to phosphorylate cyclin D1 at Thr(286), not Thr(288). Biochem J. 2014 Jan 1;457(1):43-56. doi: 10.1042/BJ20130461. PubMed PMID: 24134204.