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

General Information of Drug (ID: DM6AUHV)

• Drug Name: Fostamatinib Drug Info
• Synonyms: 901119-35-5; R788; Tavalisse; UNII-SQ8A3S5101; R-788 Free acid; R 788; R-788; R-935788 Free acid; SQ8A3S5101; R7935788; Fostamatinib [USAN:INN]

Indication

Disease Entry	ICD 11	Status	REF
Immune thrombocytopenic purpura	3B64.13	Approved	[1]
Rheumatoid arthritis	FA20	Phase 3	[2]

• Cross-matching ID:
  PubChem CID: 11671467
  CAS Number: CAS 901119-35-5
  TTD Drug ID: DM6AUHV
  VARIDT Drug ID: DR00300
  INTEDE Drug ID: DR0754
  ACDINA Drug ID: D01107

Molecule-Related Drug Atlas

Drug(s) Targeting Tyrosine-protein kinase SYK (SYK)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Fostamatinib disodium	DM3274D	Thrombocytopenia	3B64	Phase 3	[6]
Cerdulatinib	DMSCR2H	B-cell lymphoma	2A86	Phase 2	[7]
TAK-659	DMJH3U0	Diffuse large B-cell lymphoma	2A81	Phase 2	[8]
GS-9876	DM9Q2B6	Cutaneous lupus erythematosus	EB5Z	Phase 2	[9]
GS-9973	DMKWCTR	Acute myeloid leukaemia	2A60	Phase 2	[10]
Cevidoplenib	DM9QU5G	Rheumatoid arthritis	FA20	Phase 2	[11]
HM43239	DMV1SDA	Acute myeloid leukaemia	2A60	Phase 1/2	[12]
ALXN2075	DM1BSD8	Non-hodgkin lymphoma	2B33.5	Phase 1/2	[13]
SKI-O-703	DMTSKXR	Rheumatoid arthritis	FA20	Phase 1	[9]
PRT6207	DMP5CLY	Solid tumour/cancer	2A00-2F9Z	Phase 1	[14]

Drug(s) Transported By ATP-binding cassette sub-family B member 5 (ABCB5)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Doxorubicin	DMVP5YE	Acute myelogenous leukaemia	2A41	Approved	[15]
Brigatinib	DM7W94S	Anaplastic large cell lymphoma	2A90.A	Approved	[16]

Drug(s) Metabolized By Cytochrome P450 3A4 (CYP3A4)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Doxorubicin	DMVP5YE	Acute myelogenous leukaemia	2A41	Approved	[17]
Progesterone	DMUY35B	Amenorrhea	GA20.0	Approved	[18]
Tamoxifen	DMLB0EZ	Breast cancer	2C60-2C65	Approved	[19]
Estradiol	DMUNTE3	Acne vulgaris	ED80	Approved	[20]
Acetaminophen	DMUIE76	Allergic rhinitis	CA08.0	Approved	[21]
Imatinib	DM7RJXL	Acute lymphoblastic leukaemia	2A85	Approved	[22]
Etoposide	DMNH3PG	Acute myelogenous leukaemia	2A41	Approved	[23]
Zidovudine	DM4KI7O	Human immunodeficiency virus infection	1C62	Approved	[24]
Prasterone	DM67VKL	Chronic obstructive pulmonary disease	CA22	Approved	[18]
Verapamil	DMA7PEW	Angina pectoris	BA40	Approved	[25]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Tyrosine-protein kinase SYK (SYK)	TTOU65C	KSYK_HUMAN	Modulator	[3]

Drug Transporter (DTP)

DTP Name	DTP ID	UniProt ID	MOA	REF
ATP-binding cassette sub-family B member 5 (ABCB5)	DTKVEXO	ABCB5_HUMAN	Substrate	[4]

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Substrate	[5]
UDP-glucuronosyltransferase 1A9 (UGT1A9)	DE85D2P	UD19_HUMAN	Substrate	[]
Alkaline phosphatase (ALPL) Main DME	DEVEFKM	PPBT_HUMAN	Substrate	[]

References

• [1] 2018 FDA drug approvals.Nat Rev Drug Discov. 2019 Feb;18(2):85-89.
• [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: 7796).
• [3] 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: 2230).
• [4] DrugBank 5.0: a major update to the DrugBank database for 2018. Nucleic Acids Res. 2018 Jan 4;46(D1):D1074-D1082. (ID: DB12010)
• [5] Effects of CYP3A4 inhibitors ketoconazole and verapamil and the CYP3A4 inducer rifampicin on the pharmacokinetic parameters of fostamatinib: results from In vitro and phase I clinical studies. Drugs R D. 2016 Mar;16(1):81-92.
• [6] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [7] Company report (Portola Pharmaceuticals)
• [8] J Clin Oncol 32:5s, 2014 (suppl; abstr 8580).
• [9] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [10] An open-label phase 2 trial of entospletinib (GS-9973), a selective spleen tyrosine kinase inhibitor, in chronic lymphocytic leukemia. Blood. 2015 Apr 9;125(15):2336-43.
• [11] A novel selective spleen tyrosine kinase inhibitor SKI-O-703 (cevidoplenib) ameliorates lupus nephritis and serum-induced arthritis in murine models. Clin Exp Immunol. 2023 Mar 8;211(1):31-45.
• [12] Clinical pipeline report, company report or official report of Hanmi Pharmaceutical.
• [13] The Dual Syk/JAK Inhibitor Cerdulatinib Antagonizes B-cell Receptor and Microenvironmental Signaling in Chronic Lymphocytic Leukemia. Clin Cancer Res. 2017 May 1;23(9):2313-2324.
• [14] Advances in kinase inhibition: treating rheumatic diseases and beyond. Curr Opin Rheumatol. 2014 March; 26(2): 237-243.
• [15] ABCB5-mediated doxorubicin transport and chemoresistance in human malignant melanoma. Cancer Res. 2005 May 15;65(10):4320-33.
• [16] NDA/BLA Multidisciplinary Review and Evaluation of ALUNBRIG (brigatinib) From FDA.
• [17] Expression levels and activation of a PXR variant are directly related to drug resistance in osteosarcoma cell lines. Cancer. 2007 Mar 1;109(5):957-65.
• [18] Contribution of human hepatic cytochrome P450 isoforms to regioselective hydroxylation of steroid hormones. Xenobiotica. 1998 Jun;28(6):539-47.
• [19] Comprehensive evaluation of tamoxifen sequential biotransformation by the human cytochrome P450 system in vitro: prominent roles for CYP3A and CYP2D6. J Pharmacol Exp Ther. 2004 Sep;310(3):1062-75.
• [20] Isoform-specific regulation of cytochromes P450 expression by estradiol and progesterone. Drug Metab Dispos. 2013 Feb;41(2):263-9.
• [21] Metabolic interactions between acetaminophen (paracetamol) and two flavonoids, luteolin and quercetin, through in-vitro inhibition studies. J Pharm Pharmacol. 2017 Dec;69(12):1762-1772.
• [22] Potent mechanism-based inhibition of CYP3A4 by imatinib explains its liability to interact with CYP3A4 substrates. Br J Pharmacol. 2012 Apr;165(8):2787-98.
• [23] Effects of morin on the pharmacokinetics of etoposide in rats. Biopharm Drug Dispos. 2007 Apr;28(3):151-6.
• [24] The metabolism of zidovudine by human liver microsomes in vitro: formation of 3'-amino-3'-deoxythymidine. Biochem Pharmacol. 1994 Jul 19;48(2):267-76.
• [25] Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675.