CH7057288 - Moligand™, 10mM in DMSO , Inhibitor of neurotrophic receptor tyrosine kinase 1;Inhibitor of neurotrophic receptor tyrosine kinase 2;Inhibitor of neurotrophic receptor tyrosine kinase 3, CAS No.2095616-82-1, Inhibitor of neurotrophic receptor tyrosine kinase 1;Inhibitor of neurotrophic receptor tyrosine kinase 2;Inhibitor of neurotrophic receptor tyrosine kinase 3

CAS: 2095616-82-1 Cat. No.: C422540 Molecular Weight: 569.67

GRADE & PURITY Moligand™, 10mM in DMSO

Synonyms

4-​Pyridinecarboxamide,2-​[2-​[6,​11-​dihydro-​6,​6-​dimethyl-​8-​[(methylsulfonyl)​amino]​-​11-​oxobenzo[b]​naphtho[2,​3-​d]​furan-​3-​yl]​ethynyl]​-​N-​(1,​1-​dimethylethyl)​-​6-​methyl-

Storage

Store at -80°C

Shipped In

Dry ice packs + Cold packs

Overview

Information

CH7057288 is a potent and selectiveTRKinhibitor with IC50 values of 1.1 nM, 7.8 nM and 5.1 nM for TRKA, TRKB, and TRKC respectively.

Targets

TrkA (Cell-free assay); TrkC (Cell-free assay); TrkB (Cell-free assay) 1.1 nM; 5.1 nM; 7.8 nM

In vitro

CH7057288 shows selective inhibitory activity against TRKA, TRKB, and TRKC in cell-free kinase assays and suppresses proliferation of TRK fusion-positive cell lines, but not that of TRK-negative cell lines. CH7057288 suppresses mitogen-activated protein kinase (MAPK) and E2F pathways as downstream signaling of TRK fusion.

In vivo

Strong in vivo tumor growth inhibition is observed in subcutaneously implanted xenograft tumor models of TRK fusion-positive cells. Furthermore, in an intracranial implantation model mimicking brain metastasis, CH7057288 significantly induces tumor regression and improves event-free survival. CH7057288 induces potent tumor growth inhibition against all three models, with remarkable tumor regression in CUTO-3 and MO-91. CH7057288 exhibits dose-dependent exposure. Because of relatively short terminal half-life (3 to 5 hours), the plasma concentration 24 hours after dose dropped to approximately a few tenths to a hundredth of Tmax.

Cell Research(from reference)

Cell lines：The NSCLC cell line CUTO-3, CRC cell line KM12-Luc, and acute myeloid leukemia cell line MO-91 harbor MPRIP-NTRK1, TPM3-NTRK1, and ETV6-NTRK3, respectively 

Concentrations：0.01, 0.1 and 1 μM 

Incubation Time：2 h 

Specifications

Synonyms

4-​Pyridinecarboxamide, 2-​[2-​[6, ​11-​dihydro-​6, ​6-​dimethyl-​8-​[(methylsulfonyl)​amino]​-​11-​oxobenzo[b]​naphtho[2, ​3-​d]​furan-​3-​yl]​ethynyl]​-​N-​(1, ​1-​dimethylethyl)​-​6-​methyl-

Specifications & Purity

Moligand™, 10mM in DMSO

Biochemical and Physiological Mechanisms

CH7057288 is a potent and selective TRK inhibitor with IC50 values of 1.1 nM, 7.8 nM and 5.1 nM for TRKA, TRKB, and TRKC respectively.

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 neurotrophic receptor tyrosine kinase 1;Inhibitor of neurotrophic receptor tyrosine kinase 2;Inhibitor of neurotrophic receptor tyrosine kinase 3

Product Properties

• ALogP: 5.151
• hba_count: 6
• HBD Count: 2
• Rotatable Bond: 6

Names and Identifiers

• Canonical Smiles: CC1=CC(=CC(=N1)C#CC2=CC3=C(C=C2)C4=C(O3)C(C5=C(C4=O)C=CC(=C5)NS(=O)(=O)C)(C)C)C(=O)NC(C)(C)C
• IUPAC Name: N-tert-butyl-2-[2-[8-(methanesulfonamido)-6,6-dimethyl-11-oxonaphtho[2,3-b][1]benzofuran-3-yl]ethynyl]-6-methylpyridine-4-carboxamide
• InChIKey: DCGOHGQJHJXBGW-UHFFFAOYSA-N
• INCHI: 1S/C32H31N3O5S/c1-18-14-20(30(37)34-31(2,3)4)16-21(33-18)10-8-19-9-12-24-26(15-19)40-29-27(24)28(36)23-13-11-22(35-41(7,38)39)17-25(23)32(29,5)6/h9,11-17,35H,1-7H3,(H,34,37)
• Isomeric SMILES: CC1=CC(=CC(=N1)C#CC2=CC3=C(C=C2)C4=C(O3)C(C5=C(C4=O)C=CC(=C5)NS(=O)(=O)C)(C)C)C(=O)NC(C)(C)C
• Molecular Weight: 569.67
• Reaxy-Rn: 33740089
• Reaxys-RN_link_address: https://www.reaxys.com/reaxys/secured/hopinto.do?context=S&query=IDE.XRN=33740089&ln=

Taxonomic Classification

Taxonomy Tree

• Kingdom Organic compounds
  • Superclass Organoheterocyclic compounds
    • Class Naphthofurans

• Kingdom: Organic compounds
• Superclass: Organoheterocyclic compounds
• Class: Naphthofurans
• Subclass: Not available
• Intermediate Tree Nodes: Not available
• Direct Parent: Naphthofurans
• Alternative Parents: Sulfanilides Naphthalenes Pyridinecarboxamides Benzofurans Aryl ketones Methylpyridines Organosulfonamides Organic sulfonamides Heteroaromatic compounds Furans Aminosulfonyl compounds Secondary carboxylic acid amides Oxacyclic compounds Azacyclic compounds Organopnictogen compounds Organonitrogen compounds Organic oxides Hydrocarbon derivatives
• Molecular Framework: Aromatic heteropolycyclic compounds
• Substituents: Naphthofuran - Sulfanilide - Naphthalene - Pyridine carboxylic acid or derivatives - Pyridinecarboxamide - Benzofuran - Aryl ketone - Methylpyridine - Benzenoid - Organosulfonic acid amide - Organic sulfonic acid amide - Pyridine - Heteroaromatic compound - Aminosulfonyl compound - Sulfonyl - Organosulfonic acid or derivatives - Organic sulfonic acid or derivatives - Furan - Secondary carboxylic acid amide - Ketone - Carboxamide group - Oxacycle - Azacycle - Carboxylic acid derivative - Organic nitrogen compound - Organic oxygen compound - Organopnictogen compound - Organic oxide - Hydrocarbon derivative - Organosulfur compound - Organooxygen compound - Organonitrogen compound - Aromatic heteropolycyclic compound
• Description: This compound belongs to the class of organic compounds known as naphthofurans. These are compounds containing a furan ring fused to a naphthalene moiety. Furan is a 5 membered- ring aromatic ring with four carbon and one oxygen atoms. Naphthalene is a polycyclic aromatic hydrocarbon made up of two fused benzene rings.
• 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)

NTRK1 Tclin High affinity nerve growth factor receptor (2 Activities)

Discover Target: NTRK1

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

EGFR Tclin Epidermal growth factor receptor erbB1 (33727 Activities)

Discover Target: EGFR

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

INSR Tclin Insulin receptor (5558 Activities)

Discover Target: INSR

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

ERBB2 Tclin Receptor protein-tyrosine kinase erbB-2 (7851 Activities)

Discover Target: ERBB2

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

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

FGFR2 Tclin Fibroblast growth factor receptor 2 (3405 Activities)

Discover Target: FGFR2

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

SRC Tclin Tyrosine-protein kinase SRC (10310 Activities)

Discover Target: SRC

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

RAF1 Tclin Serine/threonine-protein kinase RAF (4169 Activities)

Discover Target: RAF1

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

MET Tclin Hepatocyte growth factor receptor (10718 Activities)

Discover Target: MET

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

PRKCA Tchem Protein kinase C alpha (5923 Activities)

Discover Target: PRKCA

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

NTRK1 Tclin Nerve growth factor receptor Trk-A (7922 Activities)

Discover Target: NTRK1

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

CDK1 Tchem Cyclin-dependent kinase 1 (3927 Activities)

Discover Target: CDK1

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

AKT1 Tchem Serine/threonine-protein kinase AKT (9192 Activities)

Discover Target: AKT1

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

CHEK1 Tchem Serine/threonine-protein kinase Chk1 (6846 Activities)

Discover Target: CHEK1

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

CYP3A4 Tclin Cytochrome P450 3A4 (53859 Activities)

Discover Target: CYP3A4

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

NTRK2 Tclin Neurotrophic tyrosine kinase receptor type 2 (3279 Activities)

Discover Target: NTRK2

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

ALK Tclin ALK tyrosine kinase receptor (7132 Activities)

Discover Target: ALK

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

NTRK3 Tclin NT-3 growth factor receptor (2338 Activities)

Discover Target: NTRK3

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

Associated Targets(non-human)

NIH3T3 (5395 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: 100
• DMSO(mM) Max Solubility: 175.540225042569
• Water(mg / mL) Max Solubility: ＜1
• Molecular Weight: 569.700 g/mol
• XLogP3: 5.300
• Hydrogen Bond Donor Count: 2
• Hydrogen Bond Acceptor Count: 7
• Rotatable Bond Count: 6
• Exact Mass: 569.198 Da
• Monoisotopic Mass: 569.198 Da
• Topological Polar Surface Area: 127.000 Ų
• Heavy Atom Count: 41
• Formal Charge: 0
• Complexity: 1210.000
• 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