ARV-825 - ≥97% , CAS No.1818885-28-7

CAS: 1818885-28-7 Cat. No.: A413965 Molecular Weight: 923.43

GRADE & PURITY ≥97%

Synonyms

6H-​Thieno[3,​2-​f]​[1,​2,​4]​triazolo[4,​3-​a]​[1,​4]​diazepine-​6-​acetamide,4-​(4-​chlorophenyl)​-​N-​[4-​[2-​[2-​[2-​[2-​[[2-​(2,​6-​dioxo-​3-​piperidinyl)​-​2,​3-​dihydro-​1,​3-​dioxo-​1H-​isoindol-​4-​yl]​amino]​ethoxy]​ethoxy]​ethoxy]​ethoxy]​phen

Storage

Store at -20°C

Shipped In

Ice chest + Ice pads

Application

PROTAC

Overview

Information

ARV-825 is a BRD4 Inhibitor that recruits BRD4 to the E3 ubiquitin ligase cereblon, leading to fast, efficient, and prolonged degradation of BRD4 and sustained down-regulation of MYC.

Targets

BRD4 BD2 (Cell-free assay); BRD4 BD1 (Cell-free assay) 28 nM(Kd); 90 nM(Kd)

In vitro

Compared with the BRD4 inhibitors, ARV-825 treatment results in a strikingly more pronounced effect on the levels of c-MYC, and downstream cell proliferation and apoptosis induction in BL (Burkitt’s Lymphoma) cell lines. The IC50s of ARV-825 for all tested cell lines and primary AML cells at 72 hours are in the low nanomolar range (2-50 nM). ARV-825 treatment reduces PIM1 levels and phosphorylation of CXCR4 in AML cells while overexpression of PIM1 or Myc reverses the phenomena.

In vivo

In a mouse model of human leukemia, the leukemia burdens are significantly lower in the ARV-825 treated mice as confirmed by luciferase imaging, flow cytometry, spleen size and survived longer compared to control mice.

Cell Research(from reference)

Cell lines：RS4;11 cells 

Concentrations：3, 10, 30 nM 

Incubation Time：3 h 

Specifications

Synonyms

6H-​Thieno[3, ​2-​f]​[1, ​2, ​4]​triazolo[4, ​3-​a]​[1, ​4]​diazepine-​6-​acetamide, 4-​(4-​chlorophenyl)​-​N-​[4-​[2-​[2-​[2-​[2-​[[2-​(2, ​6-​dioxo-​3-​piperidinyl)​-​2, ​3-​dihydro-​1, ​3-​dioxo-​1H-​isoindol-​4-​yl]​amino]​ethoxy]​ethoxy]​ethoxy]​ethoxy]​phen

Specifications & Purity

≥97%

Biochemical and Physiological Mechanisms

ARV-825 is a BRD4 Inhibitor that recruits BRD4 to the E3 ubiquitin ligase cereblon, leading to fast, efficient, and prolonged degradation of BRD4 and sustained down-regulation of MYC.

Storage

Store at -20°C

Shipped In

Ice chest + Ice pads

This product requires cold chain shipping. Ground and other economy services are not available.

Action Type

INHIBITOR

Purity

≥97%

Names and Identifiers

• Canonical Smiles: CC1=C(SC2=C1C(=NC(C3=NN=C(N32)C)CC(=O)NC4=CC=C(C=C4)OCCOCCOCCOCCNC5=CC=CC6=C5C(=O)N(C6=O)C7CCC(=O)NC7=O)C8=CC=C(C=C8)Cl)C
• IUPAC Name: 2-[(9S)-7-(4-chlorophenyl)-4,5,13-trimethyl-3-thia-1,8,11,12-tetrazatricyclo[8.3.0.02,6]trideca-2(6),4,7,10,12-pentaen-9-yl]-N-[4-[2-[2-[2-[2-[[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-4-yl]amino]ethoxy]ethoxy]ethoxy]ethoxy]phenyl]acetamide
• InChIKey: RWLOGRLTDKDANT-TYIYNAFKSA-N
• INCHI: 1S/C46H47ClN8O9S/c1-26-27(2)65-46-39(26)41(29-7-9-30(47)10-8-29)50-35(42-53-52-28(3)54(42)46)25-38(57)49-31-11-13-32(14-12-31)64-24-23-63-22-21-62-20-19-61-18-17-48-34-6-4-5-33-40(34)45(60)55(44(33)59)36-15-16-37(56)51-43(36)58/h4-14,35-36,48H,15-25H2,1-3H3,(H,49,57)(H,51,56,58)/t35-,36?/m0/s1
• Isomeric SMILES: CC1=C(SC2=C1C(=N[C@H](C3=NN=C(N32)C)CC(=O)NC4=CC=C(C=C4)OCCOCCOCCOCCNC5=CC=CC6=C5C(=O)N(C6=O)C7CCC(=O)NC7=O)C8=CC=C(C=C8)Cl)C
• Molecular Weight: 923.43
• Reaxy-Rn: 29518940
• Reaxys-RN_link_address: https://www.reaxys.com/reaxys/secured/hopinto.do?context=S&query=IDE.XRN=29518940&ln=

Taxonomic Classification

Taxonomy Tree

• Kingdom Organic compounds
  • Superclass Organoheterocyclic compounds
    • Class Isoindoles and derivatives
      • Subclass Isoindolines
        • Level5 Isoindolones
          • Level6 Phthalimides

• Kingdom: Organic compounds
• Superclass: Organoheterocyclic compounds
• Class: Isoindoles and derivatives
• Subclass: Isoindolines
• Intermediate Tree Nodes: Isoindolones
• Direct Parent: Phthalimides
• Alternative Parents: Alpha amino acids and derivatives Thienodiazepines Anilides Isoindoles N-arylamides Phenol ethers Phenoxy compounds Piperidinediones Secondary alkylarylamines Alkyl aryl ethers Chlorobenzenes Delta lactams 1,4-diazepines Aryl chlorides N-substituted carboxylic acid imides Vinylogous amides Triazoles Dicarboximides Heteroaromatic compounds Thiophenes N-unsubstituted carboxylic acid imides Secondary carboxylic acid amides Ketimines Dialkyl ethers Propargyl-type 1,3-dipolar organic compounds Azacyclic compounds Organic oxides Organochlorides Carbonyl compounds Hydrocarbon derivatives Organopnictogen compounds
• Molecular Framework: Aromatic heteropolycyclic compounds
• Substituents: Phthalimide - Thieno-para-diazepine - Alpha-amino acid or derivatives - Isoindole - Anilide - Piperidinedione - Phenoxy compound - Phenol ether - N-arylamide - Piperidinone - Secondary aliphatic/aromatic amine - Para-diazepine - Alkyl aryl ether - Halobenzene - Delta-lactam - Chlorobenzene - Aryl halide - Benzenoid - Monocyclic benzene moiety - Piperidine - Aryl chloride - Carboxylic acid imide, n-substituted - Azole - Heteroaromatic compound - Carboxylic acid imide - Vinylogous amide - Dicarboximide - 1,2,4-triazole - Carboxylic acid imide, n-unsubstituted - Thiophene - Secondary carboxylic acid amide - Lactam - Ketimine - Carboxamide group - Amino acid or derivatives - Secondary amine - Propargyl-type 1,3-dipolar organic compound - Carboxylic acid derivative - Azacycle - Dialkyl ether - Ether - Organic 1,3-dipolar compound - Hydrocarbon derivative - Carbonyl group - Organic oxygen compound - Organic nitrogen compound - Organic oxide - Organopnictogen compound - Organooxygen compound - Amine - Organonitrogen compound - Imine - Organochloride - Organohalogen compound - Aromatic heteropolycyclic compound
• Description: This compound belongs to the class of organic compounds known as phthalimides. These are aromatic heterocyclic compounds containing a 1,3-dioxoisoindoline moiety. They are imide derivatives of phthalic anhydrides.
• External Descriptors: Not available

Data sources

1. Djoumbou Feunang Y, Eisner R, Knox C, Chepelev L, Hastings J, Owen G, Fahy E, Steinbeck C, Subramanian S, Bolton E, Greiner R, and Wishart DS. ClassyFire: Automated Chemical Classification With A Comprehensive, Computable Taxonomy. Journal of Cheminformatics, 2016, 8:61.

DOI: 10.1186/s13321-016-0174-y

Associated Targets(Human)

BRD4 Tchem Bromodomain-containing protein 4 (1 Activities)

Discover Target: BRD4

Activity Type	Activity Value -log(M)	Mechanism of Action	Activity Reference	Publications (PubMed IDs)

CRBN Tclin Protein cereblon (1 Activities)

Discover Target: CRBN

Activity Type	Activity Value -log(M)	Mechanism of Action	Activity Reference	Publications (PubMed IDs)

HL-60 (67320 Activities)

Explore this target

Activity Type	Relation	Activity value	Units	Action Type	Journal	PubMed Id	doi	Assay Aladdin ID

MV4-11 (7307 Activities)

Explore this target

Activity Type	Relation	Activity value	Units	Action Type	Journal	PubMed Id	doi	Assay Aladdin ID

BRD4 Tchem Bromodomain-containing protein 4 (13122 Activities)

Discover Target: BRD4

Activity Type	Relation	Activity value	Units	Action Type	Journal	PubMed Id	doi	Assay Aladdin ID

RS4-11 (1012 Activities)

Explore this target

Activity Type	Relation	Activity value	Units	Action Type	Journal	PubMed Id	doi	Assay Aladdin ID

MOLM-13 (2241 Activities)

Explore this target

Activity Type	Relation	Activity value	Units	Action Type	Journal	PubMed Id	doi	Assay Aladdin ID

CRBN Tclin Protein cereblon (139 Activities)

Discover Target: CRBN

Activity Type	Relation	Activity value	Units	Action Type	Journal	PubMed Id	doi	Assay Aladdin ID

CRBN Tclin Cereblon/Ikaros (139 Activities)

Discover Target: CRBN

Activity Type	Relation	Activity value	Units	Action Type	Journal	PubMed Id	doi	Assay Aladdin ID

BRD4 Tchem Cereblon/Cullin-4A/Bromodomain-containing protein 4 (37 Activities)

Discover Target: BRD4

Activity Type	Relation	Activity value	Units	Action Type	Journal	PubMed Id	doi	Assay Aladdin ID

BRD2 Tchem Cereblon/Cullin-4A/Bromodomain-containing protein 2 (31 Activities)

Discover Target: BRD2

Activity Type	Relation	Activity value	Units	Action Type	Journal	PubMed Id	doi	Assay Aladdin ID

BRD3 Tchem Cereblon/Cullin-4A/Bromodomain-containing protein 3 (31 Activities)

Discover Target: BRD3

Activity Type	Relation	Activity value	Units	Action Type	Journal	PubMed Id	doi	Assay Aladdin ID

BRD4 Tchem Cereblon/Bromodomain-containing protein 4 (275 Activities)

Discover Target: BRD4

Activity Type	Relation	Activity value	Units	Action Type	Journal	PubMed Id	doi	Assay Aladdin ID

BRD4 Tchem von Hippel-Lindau disease tumor suppressor/Bromodomain-containing protein 4 (105 Activities)

Discover Target: BRD4

Activity Type	Relation	Activity value	Units	Action Type	Journal	PubMed Id	doi	Assay Aladdin ID

BRD4 Tchem von Hippel-Lindau disease tumor suppressor/Elongin-B/Elongin-C/Bromodomain-containing protein 4 (54 Activities)

Discover Target: BRD4

Activity Type	Relation	Activity value	Units	Action Type	Journal	PubMed Id	doi	Assay Aladdin ID

BRD2 Tchem von Hippel-Lindau disease tumor suppressor/Elongin-B/Elongin-C/Bromodomain-containing protein 2 (24 Activities)

Discover Target: BRD2

Activity Type	Relation	Activity value	Units	Action Type	Journal	PubMed Id	doi	Assay Aladdin ID

BRD3 Tchem von Hippel-Lindau disease tumor suppressor/Elongin-B/Elongin-C/Bromodomain-containing protein 3 (22 Activities)

Discover Target: BRD3

Activity Type	Relation	Activity value	Units	Action Type	Journal	PubMed Id	doi	Assay Aladdin ID

Associated Targets(non-human)

Hdac6 Histone deacetylase 6 (222 Activities)

Discover Target: Hdac6

Activity Type	Relation	Activity value	Units	Action Type	Journal	PubMed Id	doi	Assay Aladdin ID

rep Replicase polyprotein 1ab (378 Activities)

Discover Target: rep

Activity Type	Relation	Activity value	Units	Action Type	Journal	PubMed Id	doi	Assay Aladdin ID

Mechanisms of Action

Chemical and Physical Properties

• Solubility: Solubility (25°C) In vitro DMSO: 100 mg/mL (108.29 mM); Ethanol: 3 mg/mL (3.24 mM); Water: Insoluble
• Molecular Weight: 923.400 g/mol
• XLogP3: 4.800
• Hydrogen Bond Donor Count: 3
• Hydrogen Bond Acceptor Count: 14
• Rotatable Bond Count: 19
• Exact Mass: 922.288 Da
• Monoisotopic Mass: 922.288 Da
• Topological Polar Surface Area: 233.000 Ų
• Heavy Atom Count: 65
• Formal Charge: 0
• Complexity: 1720.000
• Isotope Atom Count: 0
• Defined Atom Stereocenter Count: 1
• Undefined Atom Stereocenter Count: 1
• Defined Bond Stereocenter Count: 0
• Undefined Bond Stereocenter Count: 0
• The total count of all stereochemical bonds: 0
• Covalently-Bonded Unit Count: 1