AZD5153 | CAS# 1869912-39-9 | BET Inhibitor

MedKoo Cat#: 206630 | Name: AZD5153

Description:

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

AZD5153 is a potent bivalent triazolopyridazine based Bromodomain and Extraterminal (BET) Inhibitor. AZD5153 exhibited excellent pharmacokinetic profile and exhibited high potency in vitro and in vivo effecting c-Myc downregulation and tumor growth inhibition in xenograft studies. AZD5153 showed enhanced potency as a result of bivalent binding and a clear correlation between BRD4 activity and cellular potency.

Chemical Structure

AZD5153

CAS#1869912-39-9 (free base)

Theoretical Analysis

MedKoo Cat#: 206630

Name: AZD5153

CAS#: 1869912-39-9 (free base)

Chemical Formula: C25H33N7O3

Exact Mass: 479.2645

Molecular Weight: 479.59

Elemental Analysis: C, 62.61; H, 6.94; N, 20.44; O, 10.01

Price and Availability

Size	Price	Availability
5mg	USD 350.00	2 Weeks
10mg	USD 600.00	2 Weeks
200mg	USD 2,950.00	2 Weeks

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Related CAS #

1869912-39-9 (free base) 1869912-40-2 (HNT salt)

Synonym

AZD5153; AZD-5153; AZD 5153

IUPAC/Chemical Name

(R)-4-(2-(4-(1-(3-methoxy-[1,2,4]triazolo[4,3-b]pyridazin-6-yl)piperidin-4-yl)phenoxy)ethyl)-1,3-dimethylpiperazin-2-one

InChi Key

RSMYFSPOTCDHHJ-GOSISDBHSA-N

InChi Code

InChI=1S/C25H33N7O3/c1-18-24(33)29(2)14-15-30(18)16-17-35-21-6-4-19(5-7-21)20-10-12-31(13-11-20)23-9-8-22-26-27-25(34-3)32(22)28-23/h4-9,18,20H,10-17H2,1-3H3/t18-/m1/s1

SMILES Code

O=C1N(C)CCN(CCOC2=CC=C(C3CCN(C4=NN5C(C=C4)=NN=C5OC)CC3)C=C2)[C@@H]1C

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

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# C21M11C11

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

Biological target:

A BRD4 inhibitor.

In vitro activity:

M2-like macrophage markers were significantly abrogated by AZD5153, along with those cytokines involved in immune tolerance and immune evasion, such as IL-6, IL-10, and TGF-β. The similar results occurred when it came to murine bone marrow-derived macrophages (Supplementary Figure 3C). On the other hand, iNOS, an M1 marker associated with the activated immune response of macrophages, was clearly upregulated by AZD5153. IL-12 and its family member IL-23 were also consistently and significantly increased by AZD5153 (Figure 2A). Reference: Front Immunol. 2020; 11: 89. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7058627/

In vivo activity:

As shown in Fig. 7A and B and Supplementary Fig. S9, mice injected with Mus81 knockdown cells had reduced number of lung metastasis nodes than the control group (P < 0.05). Similarly, AZD5153 treatment significantly inhibited lung metastasis compared with the control group (P < 0.05). However, AZD5153 had limited effect in the Mus81-depleted SGC7901 cells' group. H&E staining showed the pathology of lung metastasis, which confirmed that the lumps in the lung of the nude mice was formed by gastric cancer cells. IHC staining showed that AZD5153 inhibited the expression of Mus81 and ZEB1 in gastric cancer cells (Fig. 7C). Therefore, AZD5153 negatively regulated the metastasis-promoting effect of Msu81 in vivo. Reference: Mol Cancer Ther. 2019 Aug;18(8):1439-1450. https://pubmed.ncbi.nlm.nih.gov/31142662/

	Solvent	mg/mL	mM
Solubility
	DMSO	20.0	41.70
	DMF	20.0	41.70
	Ethanol	20.0	41.70
	PBS (pH 7.2)	10.0	20.85

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 479.59 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. Li X, Fu Y, Yang B, Guo E, Wu Y, Huang J, Zhang X, Xiao R, Li K, Wang B, Hu J, Sun C, Chen G. BRD4 Inhibition by AZD5153 Promotes Antitumor Immunity via Depolarizing M2 Macrophages. Front Immunol. 2020 Feb 28;11:89. doi: 10.3389/fimmu.2020.00089. PMID: 32184777; PMCID: PMC7058627. 2. Shen G, Chen J, Zhou Y, Wang Z, Ma Z, Xu C, Jiang M. AZD5153 Inhibits Prostate Cancer Cell Growth in Vitro and in Vivo. Cell Physiol Biochem. 2018;50(2):798-809. doi: 10.1159/000494244. Epub 2018 Oct 11. PMID: 30308485. 3. Zhang P, Li R, Xiao H, Liu W, Zeng X, Xie G, Yang W, Shi L, Yin Y, Tao K. BRD4 Inhibitor AZD5153 Suppresses the Proliferation of Colorectal Cancer Cells and Sensitizes the Anticancer Effect of PARP Inhibitor. Int J Biol Sci. 2019 Jul 21;15(9):1942-1954. doi: 10.7150/ijbs.34162. PMID: 31523195; PMCID: PMC6743290. 4. Yin Y, Liu W, Shen Q, Zhang P, Wang L, Tao R, Li H, Ma X, Zeng X, Cheong JH, Song S, Ajani JA, Mills GB, Tao K, Peng G. The DNA Endonuclease Mus81 Regulates ZEB1 Expression and Serves as a Target of BET4 Inhibitors in Gastric Cancer. Mol Cancer Ther. 2019 Aug;18(8):1439-1450. doi: 10.1158/1535-7163.MCT-18-0833. Epub 2019 May 29. PMID: 31142662.

In vitro protocol:

In vivo protocol:

1. Zhang P, Li R, Xiao H, Liu W, Zeng X, Xie G, Yang W, Shi L, Yin Y, Tao K. BRD4 Inhibitor AZD5153 Suppresses the Proliferation of Colorectal Cancer Cells and Sensitizes the Anticancer Effect of PARP Inhibitor. Int J Biol Sci. 2019 Jul 21;15(9):1942-1954. doi: 10.7150/ijbs.34162. PMID: 31523195; PMCID: PMC6743290. 2. Yin Y, Liu W, Shen Q, Zhang P, Wang L, Tao R, Li H, Ma X, Zeng X, Cheong JH, Song S, Ajani JA, Mills GB, Tao K, Peng G. The DNA Endonuclease Mus81 Regulates ZEB1 Expression and Serves as a Target of BET4 Inhibitors in Gastric Cancer. Mol Cancer Ther. 2019 Aug;18(8):1439-1450. doi: 10.1158/1535-7163.MCT-18-0833. Epub 2019 May 29. PMID: 31142662.

1: Bradbury RH, Callis R, Carr GR, Chen H, Clark E, Feron L, Glossop S, Graham MA, Hattersley M, Jones C, Lamont SG, Ouvry G, Patel A, Patel J, Rabow AA, Roberts CA, Stokes S, Stratton N, Walker GE, Ward L, Whalley D, Whittaker D, Wrigley G, Waring MJ. Optimization of a Series of Bivalent Triazolopyridazine Based Bromodomain and Extraterminal Inhibitors: The Discovery of (3R)-4-[2-[4-[1-(3-Methoxy-[1,2,4]triazolo[4,3-b]pyridazin-6-yl)-4-piperidyl]phen oxy]ethyl]-1,3-dimethyl-piperazin-2-one (AZD5153). J Med Chem. 2016 Aug 24. [Epub ahead of print] PubMed PMID: 27528113.