LY2857785 - ≥97% , CAS No.1619903-54-6

CAS: 1619903-54-6 Cat. No.: L413766 Molecular Weight: 448.6

GRADE & PURITY ≥97%

Synonyms

(1r,4r)-N1-(4-(3-isopropyl-2-methyl-2H-indazol-5-yl)pyrimidin-2-yl)-N4-(tetrahydro-2H-pyran-4-yl)cyclohexane-1,4-diamine

Storage

Store at -20°C

Shipped In

Ice chest + Ice pads

Overview

Information

LY2857785 is a type I reversible and competitive ATP kinase inhibitor againstCDK9(IC50=0.011 μM) and also inhibits other transcription kinasesCDK8(IC50=0.016 μM) andCDK7(IC50=0.246 μM).

Targets

CDK9 (Cell-free assay); CDK8 (Cell-free assay); CDK7 (Cell-free assay) 0.011 μM; 0.016 μM; 0.246 μM

In vitro

LY2857785 shows good selectivity against a panel of 114 protein kinases, with only 5 other protein kinases inhibited with potency (IC50) less than 0.1 μmol/L, and a total of 14 kinases less than 1 μmol/L. At the cellular level, LY2857785 inhibits CTD P-Ser2 and CTD P-Ser5 in U2OS cells at IC50s 0.089 and 0.042 μM. Although LY2857785 inhibits CDK4, CDK6, and CDK2 enzymatic activities, it does not induce G1-S cell-cycle arrest. It also has activity against CDK1 (Histone H1 P-T153 inhibition IC50 0.241 μmol/L). However LY2857785 only induces a moderate G2–M DNA content increase, from 35% to 55%, with EC50 0.135 μmol/L. LY2857785 inhibits hematologic and solid tumor cell proliferation and induces apoptosis in vitro.

In vivo

LY2857785 inhibits RNAP II CTD Ser2 phosphorylation in vivo. It demonstrates potent antitumor growth efficacy in preclinical tumor models and increases animal survival. No significant weight loss is observed in the nude mouse study while animal mortality is observed in these studies at LY2957785 high-dose groups.

Cell Research(from reference)

Cell lines：Solid tumor cells/hematologic cell lines; i.e. Human A549 (lung carcinoma), U2OS (osteosarcoma), HCT116 (colorectal carcinoma), U87MG (glioblastoma), A375 (malignant melanoma), MV-4-11 (biphenotypic B-myelomonocytic leukemia), RPMI 8226 (myelo 

Concentrations：0, 0.1, 0.2, 0.4, 0.6, 0.8, 1 μM 

Incubation Time：2-72 h 

Specifications

Synonyms

(1r, 4r)-N1-(4-(3-isopropyl-2-methyl-2H-indazol-5-yl)pyrimidin-2-yl)-N4-(tetrahydro-2H-pyran-4-yl)cyclohexane-1, 4-diamine

Specifications & Purity

≥97%

Biochemical and Physiological Mechanisms

LY2857785 is a type I reversible and competitive ATP kinase inhibitor against CDK9(IC50=0.011 μM) and also inhibits other transcription kinases CDK8(IC50=0.016 μM) and CDK7 (IC50=0.246 μM).

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

ACTIVATOR

Purity

≥97%

Names and Identifiers

• Pubchem Sid: 504772430
• Pubchem Sid Url: https://pubchem.ncbi.nlm.nih.gov/substance/504772430
• Canonical Smiles: CC(C)C1=C2C=C(C=CC2=NN1C)C3=NC(=NC=C3)NC4CCC(CC4)NC5CCOCC5
• IUPAC Name: 4-N-[4-(2-methyl-3-propan-2-ylindazol-5-yl)pyrimidin-2-yl]-1-N-(oxan-4-yl)cyclohexane-1,4-diamine
• InChIKey: LHIUZPIDLZYPRL-UHFFFAOYSA-N
• INCHI: 1S/C26H36N6O/c1-17(2)25-22-16-18(4-9-24(22)31-32(25)3)23-10-13-27-26(30-23)29-20-7-5-19(6-8-20)28-21-11-14-33-15-12-21/h4,9-10,13,16-17,19-21,28H,5-8,11-12,14-15H2,1-3H3,(H,27,29,30)
• Isomeric SMILES: CC(C)C1=C2C=C(C=CC2=NN1C)C3=NC(=NC=C3)NC4CCC(CC4)NC5CCOCC5
• Molecular Weight: 448.6
• Reaxy-Rn: 54605340
• Reaxys-RN_link_address: https://www.reaxys.com/reaxys/secured/hopinto.do?context=S&query=IDE.XRN=54605340&ln=

Taxonomic Classification

Taxonomy Tree

• Kingdom Organic compounds
  • Superclass Organoheterocyclic compounds
    • Class Benzopyrazoles
      • Subclass Indazoles

• Kingdom: Organic compounds
• Superclass: Organoheterocyclic compounds
• Class: Benzopyrazoles
• Subclass: Indazoles
• Intermediate Tree Nodes: Not available
• Direct Parent: Indazoles
• Alternative Parents: Cyclohexylamines Aminopyrimidines and derivatives Oxanes Benzenoids Pyrazoles Heteroaromatic compounds Oxacyclic compounds Dialkylamines Dialkyl ethers Azacyclic compounds Hydrocarbon derivatives
• Molecular Framework: Aromatic heteropolycyclic compounds
• Substituents: Benzopyrazole - Indazole - Aminopyrimidine - Cyclohexylamine - Oxane - Pyrimidine - Benzenoid - Pyrazole - Heteroaromatic compound - Azole - Secondary amine - Ether - Secondary aliphatic amine - Dialkyl ether - Azacycle - Oxacycle - Organic nitrogen compound - Amine - Organooxygen compound - Organonitrogen compound - Hydrocarbon derivative - Organic oxygen compound - Aromatic heteropolycyclic compound
• Description: This compound belongs to the class of organic compounds known as indazoles. These are compounds containing an indazole, which is structurally characterized by a pyrazole fused to a benzene.
• 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)

CDK9 Tchem Cyclin-dependent kinase 9 (2495 Activities)

Discover Target: CDK9

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

CDK2 Tchem Cyclin-dependent kinase 2 (9050 Activities)

Discover Target: CDK2

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

CCNT1 Tchem CDK9/cyclin T1 (2643 Activities)

Discover Target: CCNT1

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

CCNH Tbio CDK7/Cyclin H/MNAT1 (693 Activities)

Discover Target: CCNH

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

CDK8 Tchem CDK8/Cyclin C (1054 Activities)

Discover Target: CDK8

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 Ethanol: 42 mg/mL (93.62 mM); DMSO: 23 mg/mL (51.27 mM); Water: Insoluble
• Molecular Weight: 448.600 g/mol
• XLogP3: 4.300
• Hydrogen Bond Donor Count: 2
• Hydrogen Bond Acceptor Count: 6
• Rotatable Bond Count: 6
• Exact Mass: 448.295 Da
• Monoisotopic Mass: 448.295 Da
• Topological Polar Surface Area: 76.900 Ų
• Heavy Atom Count: 33
• Formal Charge: 0
• Complexity: 606.000
• 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