Details of the Drug

General Information of Drug (ID: DM4HLK3)

Drug Name
GSK-1838705A
Synonyms GSK 1838705A; GSK1838705A
Indication
Disease Entry ICD 11 Status REF
Discovery agent N.A. Investigative [1]
Drug Type
Small molecular drug
Structure
3D MOL is unavailable 2D MOL
#Ro5 Violations (Lipinski): 1 Molecular Weight (mw) 532.6
Topological Polar Surface Area (xlogp) 3.8
Rotatable Bond Count (rotbonds) 8
Hydrogen Bond Donor Count (hbonddonor) 4
Hydrogen Bond Acceptor Count (hbondacc) 9
Chemical Identifiers
Formula
C27H29FN8O3
IUPAC Name
2-[[2-[[1-[2-(dimethylamino)acetyl]-5-methoxy-2,3-dihydroindol-6-yl]amino]-7H-pyrrolo[2,3-d]pyrimidin-4-yl]amino]-6-fluoro-N-methylbenzamide
Canonical SMILES
CNC(=O)C1=C(C=CC=C1F)NC2=NC(=NC3=C2C=CN3)NC4=C(C=C5CCN(C5=C4)C(=O)CN(C)C)OC
InChI
InChI=1S/C27H29FN8O3/c1-29-26(38)23-17(28)6-5-7-18(23)31-25-16-8-10-30-24(16)33-27(34-25)32-19-13-20-15(12-21(19)39-4)9-11-36(20)22(37)14-35(2)3/h5-8,10,12-13H,9,11,14H2,1-4H3,(H,29,38)(H3,30,31,32,33,34)
InChIKey
HZTYDQRUAWIZRE-UHFFFAOYSA-N
Cross-matching ID
PubChem CID
25182616
ChEBI ID
CHEBI:93768
CAS Number
1116235-97-2
TTD ID
D06PJW

Molecular Interaction Atlas of This Drug


Drug Therapeutic Target (DTT)
DTT Name DTT ID UniProt ID MOA REF
ALK tyrosine kinase receptor (ALK) TTPMQSO ALK_HUMAN Inhibitor [1]
IGF1R messenger RNA (IGF1R mRNA) TTQFBMY IGF1R_HUMAN Inhibitor [2]
Insulin receptor (INSR) TTCBFJO INSR_HUMAN Inhibitor [1]
Ribosomal protein S6 kinase alpha-1 (RSK1) TTIXKA4 KS6A1_HUMAN Inhibitor [1]
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This Drug

Molecular Expression Atlas of This Drug

The Studied Disease Discovery agent
ICD Disease Classification N.A.
Molecule Name Molecule Type Gene Name p-value Fold-Change Z-score
Insulin receptor (INSR) DTT INSR 1.03E-05 0.26 0.66
Molecular Expression Atlas (MEA) Jump to Detail Molecular Expression Atlas of This Drug

References

1 GSK1838705A inhibits the insulin-like growth factor-1 receptor and anaplastic lymphoma kinase and shows antitumor activity in experimental models of human cancers. Mol Cancer Ther. 2009 Oct;8(10):2811-20.
2 Comprehensive analysis of kinase inhibitor selectivity. Nat Biotechnol. 2011 Oct 30;29(11):1046-51.
3 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
4 2018 FDA drug approvals.Nat Rev Drug Discov. 2019 Feb;18(2):85-89.
5 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2019
6 2017 FDA drug approvals.Nat Rev Drug Discov. 2018 Feb;17(2):81-85.
7 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: 7397).
8 CH5424802, a selective ALK inhibitor capable of blocking the resistant gatekeeper mutant. Cancer Cell. 2011 May 17;19(5):679-90.
9 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
10 PF-06463922, an ALK/ROS1 Inhibitor, Overcomes Resistance to First and Second Generation ALK Inhibitors in Preclinical Models. Cancer Cell. 2015 Jul 13;28(1):70-81.
11 Interpreting expression profiles of cancers by genome-wide survey of breadth of expression in normal tissues. Genomics 2005 Aug;86(2):127-41.
12 Clinical pipeline report, company report or official report of Antisense Therapeutics.
13 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. (Target id: 1801).
14 Specific inhibition of insulin-like growth factor-1 and insulin receptor tyrosine kinase activity and biological function by tyrphostins. Endocrinology. 1997 Apr;138(4):1427-33.
15 Diarylureas are small-molecule inhibitors of insulin-like growth factor I receptor signaling and breast cancer cell growth. Mol Cancer Ther. 2006 Apr;5(4):1079-86.
16 Optimization of a series of 4,6-bis-anilino-1H-pyrrolo[2,3-d]pyrimidine inhibitors of IGF-1R: elimination of an acid-mediated decomposition pathway. Bioorg Med Chem Lett. 2009 Jan 15;19(2):373-7.
17 Ribosomal S6 kinase (RSK) modulators: a patent review.Expert Opin Ther Pat. 2016 Sep;26(9):1061-78.
18 BI-D1870 is a specific inhibitor of the p90 RSK (ribosomal S6 kinase) isoforms in vitro and in vivo. Biochem J. 2007 Jan 1;401(1):29-38.
19 Identification and SAR of squarate inhibitors of mitogen activated protein kinase-activated protein kinase 2 (MK-2). Bioorg Med Chem. 2009 May 1;17(9):3342-51.
20 New drugs for type 2 diabetes mellitus: what is their place in therapy Drugs. 2008;68(15):2131-62.
21 Knockouts model the 100 best-selling drugs--will they model the next 100 Nat Rev Drug Discov. 2003 Jan;2(1):38-51.
22 Acidic residues on the N-terminus of proinsulin C-Peptide are important for the folding of insulin precursor. J Biochem. 2002 Jun;131(6):855-9.
23 Metformin (Glucophage) inhibits tyrosine phosphatase activity to stimulate the insulin receptor tyrosine kinase. Biochem Pharmacol. 2004 Jun 1;67(11):2081-91.
24 Hope for insulin mimetic oral antidiabetic drugs. Eur J Endocrinol. 1999 Dec;141(6):561-2.
25 Insulin glulisine: a review of its use in the management of diabetes mellitus. Drugs. 2009;69(8):1035-57.
26 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. (Target id: 1800).