Details of the Drug

General Information of Drug (ID: DMP8HW1)

Drug Name

LY2157299

Synonyms

Galunisertib; 700874-72-2; LY2157299; LY 2157299; LY-2157299; UNII-3OKH1W5LZE; 4-(2-(6-methylpyridin-2-yl)-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazol-3-yl)quinoline-6-carboxamide; 3OKH1W5LZE; Galunisertib (LY2157299); AK-79916; 4-[5,6-Dihydro-2-(6-methyl-2-pyridinyl)-4H-pyrrolo[1,2-b]pyrazol-3-yl]-6-quinolinecarboxamide; 4-(2-(6-Methylpyridin-2-yl)-5,6-dihydro-4H-pyrrolo-[1,2-b]pyrazol-3-yl)quinoline-6-carboxamide; 4-[2-(6-methylpyridin-2-yl)-4H,5H,6H-pyrrolo[1,2-b]pyrazol-3-yl]quinoline-6-carboxamide

Indication

Disease Entry	ICD 11	Status	REF
Arteriosclerosis	BD40	Phase 2/3	[1], [2]
Non-small-cell lung cancer	2C25.Y	Phase 2/3	[3]
Hepatocellular carcinoma	2C12.02	Phase 2	[3], [4]
Glioma	2A00.0	Phase 1/2	[4]
Solid tumour/cancer	2A00-2F9Z	Phase 1/2	[3]
Pancreatic cancer	2C10	Phase 1	[3]

Drug Type

Small molecular drug

Structure

3D MOL

2D MOL

#Ro5 Violations (Lipinski): 0

Molecular Weight (mw)

369.4

Topological Polar Surface Area (xlogp)

2.4

Rotatable Bond Count (rotbonds)

3

Hydrogen Bond Donor Count (hbonddonor)

1

Hydrogen Bond Acceptor Count (hbondacc)

4

Chemical Identifiers

Formula: C22H19N5O
IUPAC Name: 4-[2-(6-methylpyridin-2-yl)-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazol-3-yl]quinoline-6-carboxamide
Canonical SMILES: CC1=NC(=CC=C1)C2=NN3CCCC3=C2C4=C5C=C(C=CC5=NC=C4)C(=O)N
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

Cross-matching ID

PubChem CID: 10090485
ChEBI ID: CHEBI:137064
CAS Number: 700874-72-2
DrugBank ID: DB11911
TTD ID: D06TFI

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
TGF-beta receptor type I (TGFBR1)	TTP4520	TGFR1_HUMAN	Modulator	[5]
Transforming growth factor beta 1 (TGFB1)	TTR9XHZ	TGFB1_HUMAN	Inhibitor	[3], [4]

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Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This Drug

Molecular Expression Atlas of This Drug

The Studied Disease

Arteriosclerosis

ICD Disease Classification

BD40

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
Transforming growth factor beta 1 (TGFB1)	DTT	TGFB1	5.95E-09	1.68	7.81

Molecular Expression Atlas (MEA)

MEA Detail

Jump to Detail Molecular Expression Atlas of This Drug

References

1	URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7797).
2	ClinicalTrials.gov (NCT02008318) A Study of LY2157299 in Participants With Myelodysplastic Syndromes. U.S. National Institutes of Health.
3	Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
4	Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
5	Cardiac Safety of TGF-beta Receptor I Kinase Inhibitor LY2157299 Monohydrate in Cancer Patients in a First-in-Human Dose Study. Cardiovasc Toxicol. 2015 Oct;15(4):309-23.
6	Interpreting expression profiles of cancers by genome-wide survey of breadth of expression in normal tissues. Genomics 2005 Aug;86(2):127-41.
7	Development of TGF-beta signalling inhibitors for cancer therapy. Nat Rev Drug Discov. 2004 Dec;3(12):1011-22.
8	Clinical pipeline report, company report or official report of Sumitomo Dainippon Pharma.
9	Novel potent inhibitor of Bcr-Abl mutated imatinib resistant chronic myeloid leukemia cell lines. Cancer Research. 06/2012; 72(8 Supplement):1822-1822.
10	Targeting the TGF pathway for cancer therapy. Pharmacol Ther. 2015 Mar;147:22-31.
11	Pyrazolone based TGFbetaR1 kinase inhibitors. Bioorg Med Chem Lett. 2010 Jan 1;20(1):326-9.
12	TGF-beta type I receptor kinase inhibitor down-regulates rheumatoid synoviocytes and prevents the arthritis induced by type II collagen antibody. Int Immunol. 2007 Feb;19(2):117-26.
13	US patent application no. 2013,0028,978, Compositions and methods for wound treatment.
14	Synthesis and structure-activity relationships of a novel and selective bone morphogenetic protein receptor (BMP) inhibitor derived from the pyrazolo[1.5-a]pyrimidine scaffold of dorsomorphin: the discovery of ML347 as an ALK2 versus ALK3 selective MLPCN probe. Bioorg Med Chem Lett. 2013 Jun 1;23(11):3248-52.
15	Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
16	Clinical pipeline report, company report or official report of Tissue Gene, Inc.
17	Perspectives of TGF-beta inhibition in pancreatic and hepatocellular carcinomas. Oncotarget. 2014 January; 5(1): 78-94.
18	Clinical pipeline report, company report or official report of Scholar Rock.
19	Clinical pipeline report, company report or official report of AbbVie.
20	The mannose-6-phosphate analogue, PXS64, inhibits fibrosis via TGF-beta1 pathway in human lung fibroblasts. Immunol Lett. 2015 Jun;165(2):90-101.
21	Pharmaceutical products of TORREYA partners. December 2011.