Details of the Drug-Related molecule(s) Interaction Atlas

General Information of Drug (ID: DM4HLK3)

• Drug Name: GSK-1838705A Drug Info
• Synonyms: GSK 1838705A; GSK1838705A

Indication

Disease Entry	ICD 11	Status	REF
Discovery agent	N.A.	Investigative	[1]

• Cross-matching ID:
  PubChem CID: 25182616
  ChEBI ID: CHEBI:93768
  CAS Number: CAS 1116235-97-2
  TTD Drug ID: DM4HLK3

Molecule-Related Drug Atlas

Drug(s) Targeting ALK tyrosine kinase receptor (ALK)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Crizotinib	DM4F29C	Non-small-cell lung cancer	2C25.Y	Approved	[3]
Lorlatinib	DMICDLV	Non-small-cell lung cancer	2C25.Y	Approved	[4]
Entrectinib	DMMPTLH	Non-small cell lung cancer	2C25	Approved	[5]
Brigatinib	DM7W94S	Anaplastic large cell lymphoma	2A90.A	Approved	[6]
Ceritinib	DMB920Z	Non-small-cell lung cancer	2C25.Y	Approved	[7]
Alectinib	DMP1I6Y	Lung cancer	2C25.0	Approved	[8]
Ensartinib	DMIKDCQ	Non-small-cell lung cancer	2C25.Y	Phase 3	[9]
PF-06463922	DMKM7EW	Non-small-cell lung cancer	2C25.Y	Phase 2	[10]
AP26113	DMYBQEF	Solid tumour/cancer	2A00-2F9Z	Phase 2	[11]
TPX-0005	DM9FB2T	Solid tumour/cancer	2A00-2F9Z	Phase 1/2	[9]

Drug(s) Targeting IGF1R messenger RNA (IGF1R mRNA)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
ATL-1101	DM4XZU2	Psoriatic disorder	EA90	Preclinical	[12]
AZD3463	DMAX9C3	Discovery agent	N.A.	Investigative	[13]
AG 1024	DMF0SPB	Discovery agent	N.A.	Investigative	[14]
PQ401	DMVNHTE	Discovery agent	N.A.	Investigative	[15]
GSK1511931	DMZUTXW	Discovery agent	N.A.	Investigative	[16]

Drug(s) Targeting Ribosomal protein S6 kinase alpha-1 (RSK1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
1,6-diazanaphthalenes and pyrido[2,3-d] pyrimidine derivative 1	DMUQ9CF	N. A.	N. A.	Patented	[17]
Heterocyclic derivative 26	DM56T1P	N. A.	N. A.	Patented	[17]
1,6-diazanaphthalenes and pyrido[2,3-d] pyrimidine derivative 2	DMPZ0U8	N. A.	N. A.	Patented	[17]
Pyrrolo[2,3-d]pyrimidine derivative 1	DMYUEA6	N. A.	N. A.	Patented	[17]
Pyrrolo[2,3-d]pyrimidine derivative 2	DMJFYK1	N. A.	N. A.	Patented	[17]
BI-D1870	DMK3SAF	Chronic lymphocytic leukaemia	2A82.0	Preclinical	[18]
PMID19364658C33	DMSE1C3	Discovery agent	N.A.	Investigative	[19]

Drug(s) Targeting Insulin receptor (INSR)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Meglitinides	DM1OFHN	Type-2 diabetes	5A11	Approved	[20]
Human neutral insulin	DMA5OBU	Diabetic complication	5A2Y	Approved	[21]
Insulin Lyspro recombinant	DM5XHVR	Diabetic complication	5A2Y	Approved	[21]
Insulin, porcine	DMO95XI	Diabetic complication	5A2Y	Approved	[22]
Insulin recombinant	DMYVP5G	Diabetic complication	5A2Y	Approved	[21]
Metformin arginine-hemisuccinimide	DMTPAM3	Type-2 diabetes	5A11	Approved	[23]
Insulin-lispro	DM4O90W	Diabetic complication	5A2Y	Approved	[24]
Insulin-glulisine	DMQI0FU	Diabetic complication	5A2Y	Approved	[25]
Ryzodeq	DMOFP18	Type-2 diabetes	5A11	Approved	[26]
NN5401	DM0QV27	Diabetic complication	5A2Y	Phase 3	[26]

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]

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).