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

General Information of Drug (ID: )

• Drug Name: Drug Info

Indication

Disease Entry	ICD 11	Status	REF
Diabetic complication	5A2Y	Phase 3	[1]
Advanced solid tumour	2A00-2F9Z	Phase 1	[2]

• Cross-matching ID: TTD Drug ID

Molecule-Related Drug Atlas

Drug(s) Targeting Aurora kinase B (AURKB)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
AT9283	DMQ94CT	Solid tumour/cancer	2A00-2F9Z	Phase 3	[5]
PHA-739358	DMGYBZI	Prostate cancer	2C82.0	Phase 2	[6]
VX-680	DM93YKJ	Solid tumour/cancer	2A00-2F9Z	Phase 2	[3]
ABT-348	DMMZOYN	Haematological malignancy	2B33.Y	Phase 2	[7]
HPP-607	DM5VSZR	Solid tumour/cancer	2A00-2F9Z	Phase 1	[8]
CYC116	DMUMHXT	Solid tumour/cancer	2A00-2F9Z	Phase 1	[9]
AMG 900	DMASGXJ	Solid tumour/cancer	2A00-2F9Z	Phase 1	[10]
SNS-314	DMAC5F2	Solid tumour/cancer	2A00-2F9Z	Phase 1	[11]
BI-847325	DMY4B6J	Solid tumour/cancer	2A00-2F9Z	Phase 1	[12]
R763	DME0CJ9	Haematological malignancy	2B33.Y	Phase 1	[13]

Drug(s) Targeting Fibroblast growth factor receptor 1 (FGFR1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Romiplostim	DM3U7SZ	Thrombocytopenia	3B64	Approved	[14]
Intedanib	DMSTA36	Colorectal cancer	2B91.Z	Approved	[15]
Pemigatinib	DM819JF	Cholangiocarcinoma	2C12.10	Approved	[16]
Infigratinib	DMNKBEC	Cholangiocarcinoma	2C12.10	Approved	[17]
E-3810	DM42PFT	Solid tumour/cancer	2A00-2F9Z	Phase 3	[18]
Sulfatinib	DMPOTM4	Neuroendocrine cancer	2B72.1	Phase 3	[19]
ARQ-087	DM02BVQ	Intrahepatic cholangiocarcinoma	2C12.10	Phase 3	[20]
AZD4547	DM3827C	Solid tumour/cancer	2A00-2F9Z	Phase 2/3	[21]
Debio 1347	DMZW50O	Solid tumour/cancer	2A00-2F9Z	Phase 2	[22]
AM-001	DMGVQI8	Actinic keratosis	EK90.0	Phase 2	[23]

Drug(s) Targeting Platelet-derived growth factor receptor (PDGFR)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Imatinib	DM7RJXL	Acute lymphoblastic leukaemia	2A85	Approved	[3]
Pazopanib HCl	DM6U9CQ	Renal cell carcinoma	2C90	Approved	[24]
Intedanib	DMSTA36	Colorectal cancer	2B91.Z	Approved	[15]
CT-102	DMB8PF3	Diabetic foot ulcer	BD54	Approved	[25]
Trapidil	DMY67U8	Acute coronary syndrome	BA41	Phase 4	[26]
TKI258	DMYLT67	Renal cell carcinoma	2C90	Phase 3	[3]
BAY-57-9352	DMVA5NS	Gastric adenocarcinoma	2B72	Phase 2	[3]
X-82	DMW1NKO	Age-related macular degeneration	9B75.0	Phase 2	[27]
Vorolanib	DMIM1U9	Non-small-cell lung cancer	2C25	Phase 2	[28]
PMID25623274-Compound-WO2014132220C2	DMXEZWP	Pulmonary arterial hypertension	BB01.0	Patented	[29]

Drug(s) Targeting Peroxisome proliferator-activated receptor gamma (PPAR-gamma)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Troglitazone	DM3VFPD	Diabetic complication	5A2Y	Approved	[30]
Pioglitazone	DMKJ485	Amyotrophic lateral sclerosis	8B60.0	Approved	[31]
Lobeglitazone	DMHY3IP	Type-2 diabetes	5A11	Approved	[32]
Rosiglitazone XR	DMT45MU	Type-2 diabetes	5A11	Approved	[4]
Thiazolidinedione	DMC1NBW	Alzheimer disease	8A20	Approved	[31]
Glitazone	DMDN4A1	N. A.	N. A.	Phase 4	[33]
MURAGLITAZAR	DMG3NFZ	N. A.	N. A.	Phase 3	[34]
Rivoglitazone	DMBY31K	Ocular inflammation	9C61.24	Phase 3	[35]
Balaglitazone	DMXBHR6	Type-1 diabetes	5A10	Phase 3	[36]
Ragaglitazar	DMFSHEM	Type-1 diabetes	5A10	Phase 3	[37]

Drug(s) Targeting Vascular endothelial growth factor receptor 2 (KDR)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Sorafenib	DMS8IFC	Adenocarcinoma	2D40	Approved	[38]
Romiplostim	DM3U7SZ	Thrombocytopenia	3B64	Approved	[14]
Regorafenib	DMHSY1I	Gastrointestinal stromal tumour	2B5B	Approved	[39]
Sunitinib	DMCBJSR	Acute undifferentiated leukemia		Approved	[40]
Axitinib	DMGVH6N	Renal cell carcinoma	2C90	Approved	[41]
Vandetanib	DMRICNP	Solid tumour/cancer	2A00-2F9Z	Approved	[3]
Pazopanib HCl	DM6U9CQ	Renal cell carcinoma	2C90	Approved	[24]
Fruquintinib	DMHOSCQ	Colorectal cancer	2B91.Z	Approved	[42]
Cabozantinib	DMIYDT4	Medullary thyroid gland carcinoma		Approved	[43]
Tivozanib	DMUKC5L	Renal cell carcinoma	2C90	Approved	[44]

Drug(s) Targeting Aurora kinase A (AURKA)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
AT9283	DMQ94CT	Solid tumour/cancer	2A00-2F9Z	Phase 3	[5]
MLN8237	DMO8PT9	Solid tumour/cancer	2A00-2F9Z	Phase 3	[45]
PHA-739358	DMGYBZI	Prostate cancer	2C82.0	Phase 2	[6]
VX-680	DM93YKJ	Solid tumour/cancer	2A00-2F9Z	Phase 2	[3]
ABT-348	DMMZOYN	Haematological malignancy	2B33.Y	Phase 2	[7]
ENMD-2076	DMJZVPB	Acute myeloid leukaemia	2A60	Phase 2	[6]
LY3295668	DM8RJTB	Solid tumour/cancer	2A00-2F9Z	Phase 1/2	[46]
HPP-607	DM5VSZR	Solid tumour/cancer	2A00-2F9Z	Phase 1	[8]
MLN8054	DMUANF3	Solid tumour/cancer	2A00-2F9Z	Phase 1	[3]
CYC116	DMUMHXT	Solid tumour/cancer	2A00-2F9Z	Phase 1	[9]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Aurora kinase A (AURKA)	TTPS3C0	AURKA_HUMAN	Inhibitor	[3]
Aurora kinase B (AURKB)	TT5LS6T	AURKB_HUMAN	Inhibitor	[3]
Fibroblast growth factor receptor 1 (FGFR1)	TTRLW2X	FGFR1_HUMAN	Inhibitor	[3]
Peroxisome proliferator-activated receptor gamma (PPAR-gamma)	TTZMAO3	PPARG_HUMAN	Agonist	[4]
Platelet-derived growth factor receptor (PDGFR)	TTI2WET	NOUNIPROTAC	Inhibitor	[3]
Vascular endothelial growth factor receptor 2 (KDR)	TTUTJGQ	VGFR2_HUMAN	Inhibitor	[3]

References

• [1] ClinicalTrials.gov (NCT00499707) Efficacy and Safety Study of Rosiglitazone/Metformin Therapy vs Rosiglitazone and Metformin in Type 2 Diabetes Subjects. U.S. National Institutes of Health.
• [2] 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: 7816).
• [3] A comparison of physicochemical property profiles of marketed oral drugs and orally bioavailable anti-cancer protein kinase inhibitors in clinical development. Curr Top Med Chem. 2007;7(14):1408-22.
• [4] Clinical pipeline report, company report or official report of GlaxoSmithKline (2009).
• [5] A phase I trial of AT9283 (a selective inhibitor of aurora kinases) in children and adolescents with solid tumors: a Cancer Research UK study. Clin Cancer Res. 2015 Jan 15;21(2):267-73.
• [6] Cell cycle kinases as therapeutic targets for cancer. Nat Rev Drug Discov. 2009 Jul;8(7):547-66.
• [7] Preclinical characterization of ABT-348, a kinase inhibitor targeting the aurora, vascular endothelial growth factor receptor/platelet-derived growth factor receptor, and Src kinase families. J Pharmacol Exp Ther. 2012 Dec;343(3):617-27.
• [8] 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: 1936).
• [9] Clinical pipeline report, company report or official report of Cyclacel.
• [10] Preclinical evaluation of AMG 900, a novel potent and highly selective pan-aurora kinase inhibitor with activity in taxane-resistant tumor cell lines. Cancer Res. 2010 Dec 1;70(23):9846-54.
• [11] SNS-314, a pan-Aurora kinase inhibitor, shows potent anti-tumor activity and dosing flexibility in vivo. Cancer Chemother Pharmacol. 2010 Mar;65(4):707-17.
• [12] doi: 10.1158/1535-7163.TARG-13-B281
• [13] Preclinical characterization of Aurora kinase inhibitor R763/AS703569 identified through an image-based phenotypic screen. J Cancer Res Clin Oncol. 2010 Jan;136(1):99-113.
• [14] Anthranilic acid amides: a novel class of antiangiogenic VEGF receptor kinase inhibitors. J Med Chem. 2002 Dec 19;45(26):5687-93.
• [15] 2014 FDA drug approvals. Nat Rev Drug Discov. 2015 Feb;14(2):77-81.
• [16] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2020
• [17] Pharmacological inhibition of fibroblast growth factor (FGF) receptor signaling ameliorates FGF23-mediated hypophosphatemic rickets. J Bone Miner Res. 2013 Apr;28(4):899-911.
• [18] E-3810 is a potent dual inhibitor of VEGFR and FGFR that exerts antitumor activity in multiple preclinical models. Cancer Res. 2011 Feb 15;71(4):1396-405.
• [19] Clinical pipeline report, company report or official report of Hutchison Medi Pharma.
• [20] 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: 1808).
• [21] AZD4547: an orally bioavailable, potent, and selective inhibitor of the fibroblast growth factor receptor tyrosine kinase family. Cancer Res. 2012 Apr 15;72(8):2045-56.
• [22] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [23] Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800029917)
• [24] Hughes B: 2009 FDA drug approvals. Nat Rev Drug Discov. 2010 Feb;9(2):89-92.
• [25] Emerging drugs for diabetic foot ulcers. Expert Opin Emerg Drugs. 2006 Nov;11(4):709-24.
• [26] Osteitis fibrosa is mediated by Platelet-Derived Growth Factor-A via a phosphoinositide 3-kinase-dependent signaling pathway in a rat model for chr... Endocrinology. 2008 Nov;149(11):5735-46.
• [27] National Cancer Institute Drug Dictionary (drug id 695817).
• [28] Vorolanib, an oral VEGFR/PDGFR dual tyrosine kinase inhibitor for treatment of patients with advanced solid tumors: An open-label, phase I dose escalation and dose expansion trial. Chin J Cancer Res. 2021 Feb 28;33(1):103-114.
• [29] Evaluation of WO-2014132220, selective PDGFR inhibitors for the treatment of pulmonary arterial hypertension.Expert Opin Ther Pat. 2015 Apr;25(4):493-9.
• [30] Expression of peroxisome proliferator-activated receptors (PPARs) in human urinary bladder carcinoma and growth inhibition by its agonists. Int J Cancer. 2003 May 1;104(5):597-602.
• [31] Functional PPAR-gamma receptor is a novel therapeutic target for ACTH-secreting pituitary adenomas. Nat Med. 2002 Nov;8(11):1281-7.
• [32] Tolerability and pharmacokinetics of lobeglitazone, a novel peroxisome proliferator-activated receptor-gamma agonist, after a single oral administration in healthy female subjects. Clin Drug Investig. 2014 Jul;34(7):467-74.
• [33] Peroxisome proliferator-activated receptor alpha activators improve insulin sensitivity and reduce adiposity. J Biol Chem. 2000 Jun 2;275(22):16638-42.
• [34] Muraglitazar, a dual (alpha/gamma) PPAR activator: a randomized, double-blind, placebo-controlled, 24-week monotherapy trial in adult patients with... Clin Ther. 2005 Aug;27(8):1181-95.
• [35] A randomized-controlled trial to investigate the effects of rivoglitazone, a novel PPAR gamma agonist on glucose-lipid control in type 2 diabetes. Diabetes Obes Metab. 2011 Sep;13(9):806-13.
• [36] Balaglitazone: a second generation peroxisome proliferator-activated receptor (PPAR) gamma () agonist.Mini Rev Med Chem.2012 Feb;12(2):87-97.
• [37] Ragaglitazar: the pharmacokinetics, pharmacodynamics, and tolerability of a novel dual PPAR alpha and gamma agonist in healthy subjects and patients with type 2 diabetes. J Clin Pharmacol. 2003 Nov;43(11):1244-56.
• [38] Preclinical overview of sorafenib, a multikinase inhibitor that targets both Raf and VEGF and PDGF receptor tyrosine kinase signaling.Mol Cancer Ther.2008 Oct;7(10):3129-40.
• [39] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [40] 2006 drug approvals: finding the niche. Nat Rev Drug Discov. 2007 Feb;6(2):99-101.
• [41] Nat Rev Drug Discov. 2013 Feb;12(2):87-90.
• [42] Discovery of fruquintinib, a potent and highly selective small molecule inhibitor of VEGFR 1, 2, 3 tyrosine kinases for cancer therapy. Cancer Biol Ther. 2014;15(12):1635-45.
• [43] Clinical pipeline report, company report or official report of Exelixis (2011).
• [44] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services
• [45] Effect of Aurora A kinase inhibitor MLN8237 combined with rituximab on antitumor activity in preclinical B-cell non-Hodgkin's lymphoma models. Journal of Clinical Oncology, 2009:8553.
• [46] Aurora A-Selective Inhibitor LY3295668 Leads to Dominant Mitotic Arrest, Apoptosis in Cancer Cells, and Shows Potent Preclinical Antitumor Efficacy. Mol Cancer Ther. 2019 Dec;18(12):2207-2219.