AZD-4635 | CAS#1321514-06-0 | A2A receptor antagonist

MedKoo Cat#: 206930 | Name: AZD4635

Description:

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

AZD-4635, also known as HTL-1071, is an orally available, small molecule adenosine A2A receptor antagonist.

Chemical Structure

AZD4635

CAS#1321514-06-0

Theoretical Analysis

MedKoo Cat#: 206930

Name: AZD4635

CAS#: 1321514-06-0

Chemical Formula: C15H11ClFN5

Exact Mass: 315.0680

Molecular Weight: 315.74

Elemental Analysis: C, 57.06; H, 3.51; Cl, 11.23; F, 6.02; N, 22.18

Price and Availability

Size	Price	Availability
5mg	USD 90.00	Ready to ship
10mg	USD 150.00	Ready to ship
25mg	USD 250.00	Ready to ship
50mg	USD 400.00	Ready to ship
100mg	USD 700.00	Ready to ship
200mg	USD 1,250.00	Ready to ship
500mg	USD 2,650.00	Ready to ship

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Related CAS #

No Data

Synonym

imaradenant; AZD-4635; AZD 4635; AZD4635; HTL-1071; HTL 1071; HTL1071.

IUPAC/Chemical Name

6-(2-chloro-6-methylpyridin-4-yl)-5-(4-fluorophenyl)-1,2,4-triazin-3-amine

InChi Key

NCWQLHHDGDXIJN-UHFFFAOYSA-N

InChi Code

InChI=1S/C15H11ClFN5/c1-8-6-10(7-12(16)19-8)14-13(20-15(18)22-21-14)9-2-4-11(17)5-3-9/h2-7H,1H3,(H2,18,20,22)

SMILES Code

NC1=NC(C2=CC=C(F)C=C2)=C(C3=CC(C)=NC(Cl)=C3)N=N1

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#A8T06K22

QC Data

View QC data: current batch, Lot#A8T06K22

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

Biological target:

AZD4635 binds to human A2AR with a Ki of 1.7 nM and shows >30-fold selectivity over other adenosine receptors. In the presence of 0.1, 1 and 10 μM adenosine, the IC50s of AZD4635 for inhibition of cAMP production are 0.79, 10.0 and 142.9 nM, respectively.

In vitro activity:

The A2A receptor is a member of the G-coupled receptor family with activation leading to increased intracellular levels of cAMP. The potency of AZD4635 in inhibiting A2AR signaling was determined in a cAMP accumulation assay using CHO cells stably transfected with human A2AR (figure 1D) and stimulated with adenosine (100, 10, 1 and 0.1 µM). Owing to the competitive binding mechanism of inhibition, the antagonist activity (IC50) of AZD4635 was impacted by the adenosine concentration. As the concentration of adenosine was increased, the potency of AZD4635 antagonist activity was reduced, with a linear relationship. AZD4635 demonstrated an IC50 of 0.000794, 0.0123, 0.155 and 2.69 µM at concentrations of 0.1, 1, 10 and 100 µM adenosine. Reference: J Immunother Cancer. 2020 Jul;8(2):e000417. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7394305/

In vivo activity:

AZD4635 is an oral antagonist of the high-affinity A2A receptor, which reversed T-cell suppression ex vivo when incubated with the adenosine analog 5′-N-ethylcarboxamidoadenosine. In addition, AZD4635 partially restored CADO-mediated inhibition of T-cell proliferation (figure 4E, online supplementary figure S3C). Reference: J Immunother Cancer. 2020 May;8(1):e000610. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7239696/

	Solvent	mg/mL	mM
Solubility
	DMSO	56.7	179.42
	DMSO:PBS(pH 7.2) (1:3)	0.3	0.79
	DMF	30.0	95.01

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 315.74 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. Borodovsky A, Barbon CM, Wang Y, Ye M, Prickett L, Chandra D, Shaw J, Deng N, Sachsenmeier K, Clarke JD, Linghu B, Brown GA, Brown J, Congreve M, Cheng RK, Dore AS, Hurrell E, Shao W, Woessner R, Reimer C, Drew L, Fawell S, Schuller AG, Mele DA. Small molecule AZD4635 inhibitor of A2AR signaling rescues immune cell function including CD103+ dendritic cells enhancing anti-tumor immunity. J Immunother Cancer. 2020 Jul;8(2):e000417. doi: 10.1136/jitc-2019-000417. PMID: 32727810; PMCID: PMC7394305. 2. Yang R, Elsaadi S, Misund K, Abdollahi P, Vandsemb EN, Moen SH, Kusnierczyk A, Slupphaug G, Standal T, Waage A, Slørdahl TS, Rø TB, Rustad E, Sundan A, Hay C, Cooper Z, Schuller AG, Woessner R, Borodovsky A, Menu E, Børset M, Sponaas AM. Conversion of ATP to adenosine by CD39 and CD73 in multiple myeloma can be successfully targeted together with adenosine receptor A2A blockade. J Immunother Cancer. 2020 May;8(1):e000610. doi: 10.1136/jitc-2020-000610. PMID: 32409420; PMCID: PMC7239696.

In vitro protocol:

In vivo protocol:

1. Yang R, Elsaadi S, Misund K, Abdollahi P, Vandsemb EN, Moen SH, Kusnierczyk A, Slupphaug G, Standal T, Waage A, Slørdahl TS, Rø TB, Rustad E, Sundan A, Hay C, Cooper Z, Schuller AG, Woessner R, Borodovsky A, Menu E, Børset M, Sponaas AM. Conversion of ATP to adenosine by CD39 and CD73 in multiple myeloma can be successfully targeted together with adenosine receptor A2A blockade. J Immunother Cancer. 2020 May;8(1):e000610. doi: 10.1136/jitc-2020-000610. PMID: 32409420; PMCID: PMC7239696.

1: Jazayeri A, Andrews SP, Marshall FH. Structurally Enabled Discovery of Adenosine A(2A) Receptor Antagonists. Chem Rev. 2017 Jan 11;117(1):21-37. doi: 10.1021/acs.chemrev.6b00119. Epub 2016 Jun 22. Review. PubMed PMID: 27333206. 2. http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=9236