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

General Information of Drug (ID: DM6U9CQ)

• Drug Name: Pazopanib HCl Drug Info
• Synonyms: Votrient (TN)

Indication

Disease Entry	ICD 11	Status	REF
Renal cell carcinoma	2C90	Approved	[1]

• Cross-matching ID:
  PubChem CID: 11525740
  ChEBI ID: CHEBI:71217
  CAS Number: CAS 635702-64-6
  TTD Drug ID: DM6U9CQ
  VARIDT Drug ID: DR00185

Molecule-Related Drug Atlas

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	[4]
Intedanib	DMSTA36	Colorectal cancer	2B91.Z	Approved	[5]
CT-102	DMB8PF3	Diabetic foot ulcer	BD54	Approved	[6]
Trapidil	DMY67U8	Acute coronary syndrome	BA41	Phase 4	[7]
TKI258	DMYLT67	Renal cell carcinoma	2C90	Phase 3	[4]
BAY-57-9352	DMVA5NS	Gastric adenocarcinoma	2B72	Phase 2	[4]
X-82	DMW1NKO	Age-related macular degeneration	9B75.0	Phase 2	[8]
Vorolanib	DMIM1U9	Non-small-cell lung cancer	2C25	Phase 2	[9]
PMID25623274-Compound-WO2014132220C2	DMXEZWP	Pulmonary arterial hypertension	BB01.0	Patented	[10]
PMID25623274-Compound-WO2014132220C1	DMA2IMQ	Pulmonary arterial hypertension	BB01.0	Patented	[10]

Drug(s) Targeting Tyrosine-protein kinase Kit (KIT)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Imatinib	DM7RJXL	Acute lymphoblastic leukaemia	2A85	Approved	[4]
Sorafenib	DMS8IFC	Adenocarcinoma	2D40	Approved	[11]
Romiplostim	DM3U7SZ	Thrombocytopenia	3B64	Approved	[12]
Regorafenib	DMHSY1I	Gastrointestinal stromal tumour	2B5B	Approved	[13]
Ponatinib	DMYGJQO	Acute lymphoblastic leukaemia	2A85	Approved	[13]
Pexidartinib	DMS2J0Z	Tenosynovial giant cell tumour	2F7B	Approved	[14]
Ripretinib	DM958QB	Gastrointestinal stromal tumour	2B5B	Approved	[15]
Famitinib	DMSFWT7	Solid tumour/cancer	2A00-2F9Z	Phase 2	[16]
XL-820	DMMHX9K	Solid tumour/cancer	2A00-2F9Z	Phase 2	[17]
MP470	DMELUAK	Solid tumour/cancer	2A00-2F9Z	Phase 2	[18]

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	[11]
Romiplostim	DM3U7SZ	Thrombocytopenia	3B64	Approved	[19]
Regorafenib	DMHSY1I	Gastrointestinal stromal tumour	2B5B	Approved	[13]
Sunitinib	DMCBJSR	Acute undifferentiated leukemia		Approved	[20]
Axitinib	DMGVH6N	Renal cell carcinoma	2C90	Approved	[21]
Vandetanib	DMRICNP	Solid tumour/cancer	2A00-2F9Z	Approved	[4]
Fruquintinib	DMHOSCQ	Colorectal cancer	2B91.Z	Approved	[22]
Cabozantinib	DMIYDT4	Medullary thyroid gland carcinoma		Approved	[23]
Tivozanib	DMUKC5L	Renal cell carcinoma	2C90	Approved	[24]
Lenvatinib	DMB1IU4	Thyroid cancer	2D10	Approved	[25]

Drug(s) Transported By P-glycoprotein 1 (ABCB1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Amoxicillin	DMUYNEI	Acute otitis media	AB00	Approved	[26]
Doxorubicin	DMVP5YE	Acute myelogenous leukaemia	2A41	Approved	[27]
Methotrexate	DM2TEOL	Anterior urethra cancer		Approved	[28]
Folic Acid	DMEMBJC	Colorectal carcinoma		Approved	[29]
Fluorouracil	DMUM7HZ	Adenocarcinoma	2D40	Approved	[28]
Cisplatin	DMRHGI9	Adenocarcinoma	2D40	Approved	[28]
Progesterone	DMUY35B	Amenorrhea	GA20.0	Approved	[30]
Tamoxifen	DMLB0EZ	Breast cancer	2C60-2C65	Approved	[28]
Estradiol	DMUNTE3	Acne vulgaris	ED80	Approved	[31]
Imatinib	DM7RJXL	Acute lymphoblastic leukaemia	2A85	Approved	[32]

Drug(s) Transported By Breast cancer resistance protein (ABCG2)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Doxorubicin	DMVP5YE	Acute myelogenous leukaemia	2A41	Approved	[33]
Methotrexate	DM2TEOL	Anterior urethra cancer		Approved	[34]
Folic Acid	DMEMBJC	Colorectal carcinoma		Approved	[35]
Fluorouracil	DMUM7HZ	Adenocarcinoma	2D40	Approved	[36]
Cisplatin	DMRHGI9	Adenocarcinoma	2D40	Approved	[37]
Progesterone	DMUY35B	Amenorrhea	GA20.0	Approved	[38]
Tamoxifen	DMLB0EZ	Breast cancer	2C60-2C65	Approved	[39]
Estradiol	DMUNTE3	Acne vulgaris	ED80	Approved	[38]
Sulfasalazine	DMICA9H	Irritable bowel syndrome	DD91.0	Approved	[40]
Imatinib	DM7RJXL	Acute lymphoblastic leukaemia	2A85	Approved	[41]

Drug(s) Transported By Organic anion transporting polypeptide 1B1 (SLCO1B1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Methotrexate	DM2TEOL	Anterior urethra cancer		Approved	[42]
Dinoprostone	DMTYOPD	Medical abortion	JA00.1Z	Approved	[3]
Imatinib	DM7RJXL	Acute lymphoblastic leukaemia	2A85	Approved	[43]
Etoposide	DMNH3PG	Acute myelogenous leukaemia	2A41	Approved	[44]
Sorafenib	DMS8IFC	Adenocarcinoma	2D40	Approved	[43]
Pravastatin	DM6A0X7	Adult acute monocytic leukemia		Approved	[45]
Mycophenolate mofetil	DMPQAGE	Hepatosplenic T-cell lymphoma		Approved	[46]
Atorvastatin	DMF28YC	Acute coronary syndrome	BA41	Approved	[47]
Cerivastatin	DMXCM7H	Hyperlipidaemia	5C80	Approved	[48]
PITAVASTATIN CALCIUM	DM1UJO0	Dyslipidemia	5C80-5C81	Approved	[45]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Platelet-derived growth factor receptor (PDGFR)	TTI2WET	NOUNIPROTAC	Inhibitor	[1]
Tyrosine-protein kinase Kit (KIT)	TTX41N9	KIT_HUMAN	Inhibitor	[1]
Vascular endothelial growth factor receptor 2 (KDR)	TTUTJGQ	VGFR2_HUMAN	Inhibitor	[1]

Drug Transporter (DTP)

DTP Name	DTP ID	UniProt ID	MOA	REF
Breast cancer resistance protein (ABCG2)	DTI7UX6	ABCG2_HUMAN	Substrate	[2]
Organic anion transporting polypeptide 1B1 (SLCO1B1)	DT3D8F0	SO1B1_HUMAN	Substrate	[3]
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[2]

References

• [1] Hughes B: 2009 FDA drug approvals. Nat Rev Drug Discov. 2010 Feb;9(2):89-92.
• [2] Bioavailability, metabolism and disposition of oral pazopanib in patients with advanced cancer. Xenobiotica. 2013 May;43(5):443-53.
• [3] Organic anion transporting polypeptide 1B1: a genetically polymorphic transporter of major importance for hepatic drug uptake. Pharmacol Rev. 2011 Mar;63(1):157-81.
• [4] 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.
• [5] 2014 FDA drug approvals. Nat Rev Drug Discov. 2015 Feb;14(2):77-81.
• [6] Emerging drugs for diabetic foot ulcers. Expert Opin Emerg Drugs. 2006 Nov;11(4):709-24.
• [7] 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.
• [8] National Cancer Institute Drug Dictionary (drug id 695817).
• [9] 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.
• [10] Evaluation of WO-2014132220, selective PDGFR inhibitors for the treatment of pulmonary arterial hypertension.Expert Opin Ther Pat. 2015 Apr;25(4):493-9.
• [11] 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.
• [12] New anilinophthalazines as potent and orally well absorbed inhibitors of the VEGF receptor tyrosine kinases useful as antagonists of tumor-driven a... J Med Chem. 2000 Jun 15;43(12):2310-23.
• [13] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [14] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2019
• [15] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2020
• [16] Metabolism and bioactivation of famitinib, a novel inhibitor of receptor tyrosine kinase, in cancer patients. Br J Pharmacol. 2013 Apr;168(7):1687-706.
• [17] National Cancer Institute Drug Dictionary (drug id 452042).
• [18] Phase 1B study of amuvatinib in combination with five standard cancer therapies in adults with advanced solid tumors. Cancer Chemother Pharmacol. 2014 Jul;74(1):195-204.
• [19] Anthranilic acid amides: a novel class of antiangiogenic VEGF receptor kinase inhibitors. J Med Chem. 2002 Dec 19;45(26):5687-93.
• [20] 2006 drug approvals: finding the niche. Nat Rev Drug Discov. 2007 Feb;6(2):99-101.
• [21] Nat Rev Drug Discov. 2013 Feb;12(2):87-90.
• [22] 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.
• [23] Clinical pipeline report, company report or official report of Exelixis (2011).
• [24] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services
• [25] Emerging drugs for ovarian cancer. Expert Opin Emerg Drugs. 2008 Sep;13(3):523-36.
• [26] Human intestinal transporter database: QSAR modeling and virtual profiling of drug uptake, efflux and interactions. Pharm Res. 2013 Apr;30(4):996-1007.
• [27] MDR1 (ABCB1) G1199A (Ser400Asn) polymorphism alters transepithelial permeability and sensitivity to anticancer agents. Cancer Chemother Pharmacol. 2009 Jun;64(1):183-8.
• [28] Mammalian drug efflux transporters of the ATP binding cassette (ABC) family in multidrug resistance: A review of the past decade. Cancer Lett. 2016 Jan 1;370(1):153-64.
• [29] Folate transporter expression decreases in the human placenta throughout pregnancy and in pre-eclampsia. Pregnancy Hypertens. 2012 Apr;2(2):123-31.
• [30] Comparative studies on in vitro methods for evaluating in vivo function of MDR1 P-glycoprotein. Pharm Res. 2001 Dec;18(12):1660-8.
• [31] Antiestrogens and steroid hormones: substrates of the human P-glycoprotein. Biochem Pharmacol. 1994 Jul 19;48(2):287-92.
• [32] Association of genetic polymorphisms in the influx transporter SLCO1B3 and the efflux transporter ABCB1 with imatinib pharmacokinetics in patients with chronic myeloid leukemia. Ther Drug Monit. 2011 Apr;33(2):244-50.
• [33] Doxorubicin transport by RALBP1 and ABCG2 in lung and breast cancer. Int J Oncol. 2007 Mar;30(3):717-25.
• [34] Wild-type breast cancer resistance protein (BCRP/ABCG2) is a methotrexate polyglutamate transporter. Cancer Res. 2003 Sep 1;63(17):5538-43.
• [35] The effect of low pH on breast cancer resistance protein (ABCG2)-mediated transport of methotrexate, 7-hydroxymethotrexate, methotrexate diglutamate, folic acid, mitoxantrone, topotecan, and resveratrol in in vitro drug transport models. Mol Pharmacol. 2007 Jan;71(1):240-9.
• [36] Role of BCRP as a biomarker for predicting resistance to 5-fluorouracil in breast cancer. Cancer Chemother Pharmacol. 2009 May;63(6):1103-10.
• [37] Inhibiting the function of ABCB1 and ABCG2 by the EGFR tyrosine kinase inhibitor AG1478. Biochem Pharmacol. 2009 Mar 1;77(5):781-93.
• [38] Sterol transport by the human breast cancer resistance protein (ABCG2) expressed in Lactococcus lactis. J Biol Chem. 2003 Jun 6;278(23):20645-51.
• [39] The phytoestrogen genistein enhances multidrug resistance in breast cancer cell lines by translational regulation of ABC transporters. Cancer Lett. 2016 Jun 28;376(1):165-72.
• [40] Curcumin inhibits the activity of ABCG2/BCRP1, a multidrug resistance-linked ABC drug transporter in mice. Pharm Res. 2009 Feb;26(2):480-7.
• [41] Imatinib mesylate (STI571) is a substrate for the breast cancer resistance protein (BCRP)/ABCG2 drug pump. Blood. 2004 Nov 1;104(9):2940-2.
• [42] Preclinical Mouse Models To Study Human OATP1B1- and OATP1B3-Mediated Drug-Drug Interactions in Vivo. Mol Pharm. 2015 Dec 7;12(12):4259-69.
• [43] Contribution of OATP1B1 and OATP1B3 to the disposition of sorafenib and sorafenib-glucuronide. Clin Cancer Res. 2013 Mar 15;19(6):1458-66.
• [44] Identification of drugs and drug metabolites as substrates of multidrug resistance protein 2 (MRP2) using triple-transfected MDCK-OATP1B1-UGT1A1-MRP2 cells. Br J Pharmacol. 2012 Mar;165(6):1836-1847.
• [45] The effect of SLCO1B1*15 on the disposition of pravastatin and pitavastatin is substrate dependent: the contribution of transporting activity changes by SLCO1B1*15. Pharmacogenet Genomics. 2008 May;18(5):424-33.
• [46] Influence of SLCO1B1, 1B3, 2B1 and ABCC2 genetic polymorphisms on mycophenolic acid pharmacokinetics in Japanese renal transplant recipients. Eur J Clin Pharmacol. 2007 Dec;63(12):1161-9.
• [47] Rifampicin alters atorvastatin plasma concentration on the basis of SLCO1B1 521T>C polymorphism. Clin Chim Acta. 2009 Jul;405(1-2):49-52.
• [48] FDA Drug Development and Drug Interactions