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700874-72-2 molecular structure
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4-[2-(6-methylpyridin-2-yl)-4H,5H,6H-pyrrolo[1,2-b]pyrazol-3-yl]quinoline-6-carboxamide

ChemBase ID: 73114
Molecular Formular: C22H19N5O
Molecular Mass: 369.41916
Monoisotopic Mass: 369.15896025
SMILES and InChIs

SMILES:
c1(cccc(n1)c1c(c2ccnc3c2cc(cc3)C(=O)N)c2n(n1)CCC2)C
Canonical SMILES:
Cc1cccc(n1)c1nn2c(c1c1ccnc3c1cc(cc3)C(=O)N)CCC2
InChI:
InChI=1S/C22H19N5O/c1-13-4-2-5-18(25-13)21-20(19-6-3-11-27(19)26-21)15-9-10-24-17-8-7-14(22(23)28)12-16(15)17/h2,4-5,7-10,12H,3,6,11H2,1H3,(H2,23,28)
InChIKey:
IVRXNBXKWIJUQB-UHFFFAOYSA-N

Cite this record

CBID:73114 http://www.chembase.cn/molecule-73114.html

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NAMES AND DATABASE IDS

NAMES AND DATABASE IDS

Names Database IDs
IUPAC name
4-[2-(6-methylpyridin-2-yl)-4H,5H,6H-pyrrolo[1,2-b]pyrazol-3-yl]quinoline-6-carboxamide
IUPAC Traditional name
4-[2-(6-methylpyridin-2-yl)-4H,5H,6H-pyrrolo[1,2-b]pyrazol-3-yl]quinoline-6-carboxamide
Synonyms
LY 2157299
LY2157299
CAS Number
700874-72-2
PubChem SID
162038034
PubChem CID
10090485

DATA SOURCES

DATA SOURCES

All Sources Commercial Sources Non-commercial Sources
Data Source Data ID Price
Selleck Chemicals
S2230 external link Add to cart Please log in.
Data Source Data ID
PubChem 10090485 external link

CALCULATED PROPERTIES

CALCULATED PROPERTIES

JChem
Acid pKa 14.581796  H Acceptors
H Donor LogD (pH = 5.5) 2.6348312 
LogD (pH = 7.4) 2.6377633  Log P 2.6378007 
Molar Refractivity 117.8662 cm3 Polarizability 44.08962 Å3
Polar Surface Area 86.69 Å2 Rotatable Bonds
Lipinski's Rule of Five true 

PROPERTIES

PROPERTIES

Safety Information Pharmacology Properties Product Information Bioassay(PubChem)
Storage Condition
-20°C expand Show data source
Target
TGF-beta expand Show data source
Salt Data
Free Base expand Show data source

DETAILS

DETAILS

Selleck Chemicals Selleck Chemicals
Selleck Chemicals - S2230 external link
Research Area
Description Cancer
Biological Activity
Description LYLY2157299 is a potent TGFβ receptor I (TβRI) inhibitor with IC50 of 56 nM.
Targets TβRI
IC50 56 nM [1]
In Vitro LY2157299 potently inhibits the TGFβ receptor signaling. LY2157299 abolishes the TGFβ induced Smad2 phosphorylation in HUVEC cells. LY2157299 also shows dose dependent potentiation of VEGF or bFGF induced cell proliferation in HUVEC. LY2157299 also promotes VEGF induced HUVEC cell migration. LY2157299 potentiates angiogenesis in the in vitro VEGF-stimulated cord formation assay. [2] LY2157299 inhibits TGF-β–mediated SMAD2 activation and hematopoietic suppression in primary hematopoietic stem cells in a dose-dependent manner. LY2157199 treatment stimulates hematopoiesis from primary MDS bone marrow specimens. [3] In human glioblastoma (GBM) cells, LY2157299 treatment blocks signaling through the heteromeric TGFβ receptor complex to reduce levels of active, phosphorylated SMAD. [4]
In Vivo Although anti-tumor activity has been observed in several pre-clinical models, LY2157299 fails to show significant in vivo angiogenic effects in the 4T1, Colo205, or A549 xenograft models. [2] Administration of LY2157299 ameliorates anemia in a TGF-β overexpressing transgenic mouse model of bone marrow failure. [3] Oral administration of LY2157299 at 75 mg/kg/day displays significant antitumor activity against both Calu6 and MX1 xenografts in mice. [5] In vivo, LY2157299 induces angiogenesis and enhances VEGF and basic-fibroblast-growth-factor-induced angiogenesis in a Matrigel-plug assay, whereas adding an alpha5-integrin-neutralizing antibody to the Matrigel selectively inhibits this enhanced response. [6]
Clinical Trials A Phase II study of LY2157299 in patients with hepatocellular carcinoma is currently ongoing.
Features
Protocol
Kinase Assay [1]
TGF-β Type I (RIT204D) Receptors reaction Reactions: 170-200 nM enzyme in 1 × KB (50 mM Tris pH 7.5, 150 mM NaCl, 4 mM MgCl2, 1 mM NaF, 2 mM β-mercaptoethanol), LY2157299 dilution series in 1 × KB /16% DMSO (20 μM to 1 nM final concentration with 4% DMSO final concentration), reactions are started by adding ATP mix (4 μM ATP/ 1 μCi 33P-α-ATP final concentrations) in 1 × KB. Reactions are incubated at 30 °C for 1 hour. Reactions are stopped and quantitated using standard TCA/BSA precipitation onto Millipore FB glass fiber filter plates and by liquid scintillation counting on a MicroBeta JET.
Animal Study [5]
Animal Models Nude mice implanted subcutaneously with Calu6 or MX1 cells
Formulation Dissolved in DMSO and diluted in saline
Doses 75 mg/kg/day
Administration Orally
References
[1] Mundla SR, Patent, 2006, US7872020.
[2] Yingling JM, et al. Proc Am Assoc Cancer Res. 2006, 47, abstract 250.
[3] Zhou L, et al. Cancer Res, 2011, 71(3), 955-963.
[4] Parsons S, et al. Mol Cancer Ther, 2011, 10(11), Suppl 1, Abst C201.
[5] Bueno L, et al. Eur J Cancer, 2008, 44(1), 142-150.
[6] Liu Z, et al. J Cell Sci, 2009, 122(18), 3294-3302.

REFERENCES

REFERENCES

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PATENTS

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