WARNING: This product is for research use only, not for human or veterinary use.
Hodoodo CAT#: H407155
CAS#: 1594092-37-1
Description: 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.
Hodoodo Cat#: H407155
Name: AZ191
CAS#: 1594092-37-1
Chemical Formula: C24H27N7O
Exact Mass: 429.23
Molecular Weight: 429.530
Elemental Analysis: C, 67.11; H, 6.34; N, 22.83; O, 3.72
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:
| 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 | Max Conc. mg/mL | Max Conc. 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 |
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: | 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. 2. 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. |
| 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.
