ARN-3236 - Moligand™, 10mM in DMSO , Inhibitor of salt inducible kinase 1;Inhibitor of salt inducible kinase 2;Inhibitor of SIK family kinase 3, CAS No.1613710-01-2, Inhibitor of salt inducible kinase 1;Inhibitor of salt inducible kinase 2;Inhibitor of SIK family kinase 3

CAS: 1613710-01-2 Cat. No.: A421945 Molecular Weight: 336.41

GRADE & PURITY Moligand™, 10mM in DMSO

Synonyms

1H-​Pyrrolo[2,​3-​b]​pyridine,3-​(2,​4-​dimethoxyphenyl)​-​4-​(3-​thienyl)​-

Storage

Store at -80°C

Shipped In

Dry ice packs + Cold packs

Overview

Information

ARN-3236 ARN-3236 is a potent, orally available and selective inhibitor of salt-inducible kinase 2 (SIK2) with IC50 of <1 nM, 21.63 nM and 6.63 nM for SIK2, SIK1 and SIK3, respectively. ARN-3236 induces apoptosis in cancer cells.

Targets

SIK2 (Cell-free assay); SIK3 (Cell-free assay); SIK1 (Cell-free assay) 1 nM; 6.63 nM; 21.63 nM

In vitro

SIK2 is overexpressed in approximately 30% of high grade serous ovarian cancers. ARN-3236 inhibits growth of 10 ovarian cancer cell lines at an IC50 of 0.8 to 2.6 μM, where the IC50 of ARN-3236 is inversely correlated with endogenous SIK2 expression (Pearson’s r = −0.642, P = 0.03). ARN-3236 enhances sensitivity to paclitaxel in 8 of 10 cell lines. In at least three cell lines a synergistic interaction is observed. ARN-3236 uncouples the centrosome from the nucleus in interphase, blocks centrosome separation in mitosis, causes prometaphase arrest and induces apoptotic cell death and tetraploidy. ARN-3236 also inhibits AKT phosphorylation and attenuates survivin expression.

In vivo

The antitumor activity of ARN-3236 is measured using ovarian cancer xenograft model in nu/nu mice. In SKOv3ip xenograft model, ARN-3236 plus paclitaxel produces greater inhibition of tumor growth than any other group and showed statistically significant difference compared to paclitaxel alone (P = 0.028). ARN-3236 also inhibits SIK2 activity and enhances paclitaxel sensitivity in OVCAR8 xenografts.

Cell Research(from reference)

Cell lines：HEY, A2780, UPN251, OVCAR3, OVCAR5, OVCAR8, ES-2, OC316, SKOv3 and IGROV1 

Concentrations：1 μM, 2 μM, 3 μM, 5 μM 

Incubation Time：16 h, 24 h, 32 h, 48 h 

Specifications

Synonyms

1H-​Pyrrolo[2, ​3-​b]​pyridine, 3-​(2, ​4-​dimethoxyphenyl)​-​4-​(3-​thienyl)​-

Specifications & Purity

Moligand™, 10mM in DMSO

Biochemical and Physiological Mechanisms

ARN-3236 is a potent, orally available and selective inhibitor of salt-inducible kinase 2 (SIK2) with IC50 of <1 nM, 21.63 nM and 6.63 nM for SIK2, SIK1 and SIK3, respectively. ARN-3236 induces apoptosis in cancer cells.

Storage

Store at -80°C

Shipped In

Dry ice packs + Cold packs

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

Grade

Moligand™

Action Type

INHIBITOR

Mechanism of action

Inhibitor of salt inducible kinase 1;Inhibitor of salt inducible kinase 2;Inhibitor of SIK family kinase 3

Product Properties

• ALogP: 3.837
• hba_count: 3
• HBD Count: 1
• Rotatable Bond: 4

Names and Identifiers

• Canonical Smiles: COC1=CC(=C(C=C1)C2=CNC3=NC=CC(=C23)C4=CSC=C4)OC
• IUPAC Name: 3-(2,4-dimethoxyphenyl)-4-thiophen-3-yl-1H-pyrrolo[2,3-b]pyridine
• InChIKey: WEHOIIGXTMKVRG-UHFFFAOYSA-N
• INCHI: 1S/C19H16N2O2S/c1-22-13-3-4-15(17(9-13)23-2)16-10-21-19-18(16)14(5-7-20-19)12-6-8-24-11-12/h3-11H,1-2H3,(H,20,21)
• Isomeric SMILES: COC1=CC(=C(C=C1)C2=CNC3=NC=CC(=C23)C4=CSC=C4)OC
• Molecular Weight: 336.41
• Reaxy-Rn: 27004465
• Reaxys-RN_link_address: https://www.reaxys.com/reaxys/secured/hopinto.do?context=S&query=IDE.XRN=27004465&ln=

Taxonomic Classification

Taxonomy Tree

• Kingdom Organic compounds
  • Superclass Organoheterocyclic compounds
    • Class Pyrroles
      • Subclass Substituted pyrroles

• Kingdom: Organic compounds
• Superclass: Organoheterocyclic compounds
• Class: Pyrroles
• Subclass: Substituted pyrroles
• Intermediate Tree Nodes: Not available
• Direct Parent: Phenylpyrroles
• Alternative Parents: Dimethoxybenzenes Pyrrolopyridines Phenoxy compounds Anisoles Alkyl aryl ethers Pyridines and derivatives Thiophenes Heteroaromatic compounds Azacyclic compounds Organonitrogen compounds Hydrocarbon derivatives
• Molecular Framework: Aromatic heteropolycyclic compounds
• Substituents: 3-phenylpyrrole - M-dimethoxybenzene - Dimethoxybenzene - Pyrrolopyridine - Phenoxy compound - Anisole - Phenol ether - Methoxybenzene - Alkyl aryl ether - Monocyclic benzene moiety - Benzenoid - Pyridine - Heteroaromatic compound - Thiophene - Ether - Azacycle - Organonitrogen compound - Organic nitrogen compound - Hydrocarbon derivative - Organooxygen compound - Organic oxygen compound - Aromatic heteropolycyclic compound
• Description: This compound belongs to the class of organic compounds known as phenylpyrroles. These are polycyclic aromatic compounds containing a benzene ring linked to a pyrrole ring through a CC or CN bond.
• 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)

SIK1 Tchem Serine/threonine-protein kinase SIK1 (1 Activities)

Discover Target: SIK1

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

SIK2 Tchem Serine/threonine-protein kinase SIK2 (1 Activities)

Discover Target: SIK2

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

SIK3 Tchem Serine/threonine-protein kinase SIK3 (1 Activities)

Discover Target: SIK3

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

LCK Tclin Tyrosine-protein kinase LCK (9212 Activities)

Discover Target: LCK

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

JAK2 Tclin Tyrosine-protein kinase JAK2 (12915 Activities)

Discover Target: JAK2

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

KDR Tclin Vascular endothelial growth factor receptor 2 (20924 Activities)

Discover Target: KDR

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

HepG2 (196354 Activities)

Explore this target

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

SRPK1 Tchem Serine/threonine-protein kinase SRPK1 (2359 Activities)

Discover Target: SRPK1

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

SIK1 Tchem Serine/threonine-protein kinase SIK1 (1440 Activities)

Discover Target: SIK1

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

NUAK2 Tchem NUAK family SNF1-like kinase 2 (630 Activities)

Discover Target: NUAK2

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

SIK2 Tchem Serine/threonine-protein kinase SIK2 (1467 Activities)

Discover Target: SIK2

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

SIK3 Tchem Serine/threonine-protein kinase SIK3 (566 Activities)

Discover Target: SIK3

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

Associated Targets(non-human)

rep Replicase polyprotein 1ab (378 Activities)

Discover Target: rep

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

SARS-CoV-2 (38078 Activities)

Explore this target

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

Mechanisms of Action

Chemical and Physical Properties

• DMSO(mg / mL) Max Solubility: 67
• DMSO(mM) Max Solubility: 199.161737165958
• Water(mg / mL) Max Solubility: ＜1
• Molecular Weight: 336.400 g/mol
• XLogP3: 4.200
• Hydrogen Bond Donor Count: 1
• Hydrogen Bond Acceptor Count: 4
• Rotatable Bond Count: 4
• Exact Mass: 336.093 Da
• Monoisotopic Mass: 336.093 Da
• Topological Polar Surface Area: 75.400 Ų
• Heavy Atom Count: 24
• Formal Charge: 0
• Complexity: 424.000
• Isotope Atom Count: 0
• Defined Atom Stereocenter Count: 0
• Undefined Atom Stereocenter Count: 0
• Defined Bond Stereocenter Count: 0
• Undefined Bond Stereocenter Count: 0
• The total count of all stereochemical bonds: 0
• Covalently-Bonded Unit Count: 1